WorldWideScience

Sample records for global functional alterations

  1. Altered Global Signal Topography in Schizophrenia.

    Science.gov (United States)

    Yang, Genevieve J; Murray, John D; Glasser, Matthew; Pearlson, Godfrey D; Krystal, John H; Schleifer, Charlie; Repovs, Grega; Anticevic, Alan

    2017-11-01

    Schizophrenia (SCZ) is a disabling neuropsychiatric disease associated with disruptions across distributed neural systems. Resting-state functional magnetic resonance imaging has identified extensive abnormalities in the blood-oxygen level-dependent signal in SCZ patients, including alterations in the average signal over the brain-i.e. the "global" signal (GS). It remains unknown, however, if these "global" alterations occur pervasively or follow a spatially preferential pattern. This study presents the first network-by-network quantification of GS topography in healthy subjects and SCZ patients. We observed a nonuniform GS contribution in healthy comparison subjects, whereby sensory areas exhibited the largest GS component. In SCZ patients, we identified preferential GS representation increases across association regions, while sensory regions showed preferential reductions. GS representation in sensory versus association cortices was strongly anti-correlated in healthy subjects. This anti-correlated relationship was markedly reduced in SCZ. Such shifts in GS topography may underlie profound alterations in neural information flow in SCZ, informing development of pharmacotherapies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Anti-Globalization or Alter-Globalization? Mapping the Political Ideology of the Global Justice Movement

    NARCIS (Netherlands)

    B. Steger, Manfred; Wilson, E.K.

    Steger, Manfred B. and Erin K. Wilson. (2012) Anti-Globalization or Alter-Globalization? Mapping the Political Ideology of the Global Justice Movement. International Studies Quarterly, doi: 10.1111/j.1468-2478.2012.00740.x?(c) 2012 International Studies Association Globalization has unsettled

  3. Altered States: Globalization, Sovereignty, and Governance | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    For all the opportunities that globalization promises, it raises urgent ... Has the achievement of democratic government come too late for most of the ... The message of Altered States is one of both hope and warning: globalization opens great ...

  4. Altered nutrition during hot droughts will impair forest functions in the future

    Science.gov (United States)

    Grossiord, C.; Gessler, A.; Reed, S.; Dickman, L. T.; Collins, A.; Schönbeck, L.; Sevanto, S.; Vilagrosa, A.; McDowell, N. G.

    2017-12-01

    Rising greenhouse gas emissions will increase atmospheric temperature globally and alter hydrological cycles resulting in more extreme and recurrent droughts in the coming century. Nutrition is a key component affecting the vulnerability of forests to extreme climate. Models typically assume that global warming will enhance nitrogen cycling in terrestrial ecosystems and lead to improved plant functions. Drought on the other hand is expected to weaken the same processes, leading to a clear conflict and inability to predict how nutrition and plant functions will be impacted by a simultaneously warming and drying climate. We used a unique setup consisting of long-term manipulation of climate on mature trees to examine how individual vs. combined warming and drought would alter soil N cycling and tree functions. The site consists of the longest record of tree responses to experimental warming and precipitation reduction in natural conditions.Changes in soil nitrogen cycling (e.g. microbial activity, nitrification and ammonification rates, N concentration) occurred in response to the treatments. In addition, temperature rise and precipitation reduction altered the ability of trees to take up nitrogen and modified nitrogen allocation patterns between aboveground and belowground compartments. Although no additive effect of warming and drying were found for the two studied species, contrasting responses to warming and droughts were observed between the two functional types. Overall, our results show that higher temperature and reduced precipitation will alter the nutrition of forest ecosystems in the future with potentially large consequences for forest functions, structure and biodiversity.

  5. Alteration of consciousness in focal epilepsy: the global workspace alteration theory.

    Science.gov (United States)

    Bartolomei, Fabrice; McGonigal, Aileen; Naccache, Lionel

    2014-01-01

    Alteration of consciousness (AOC) is an important clinical manifestation of partial seizures that greatly impacts the quality of life of patients with epilepsy. Several theories have been proposed in the last fifty years. An emerging concept in neurology is the global workspace (GW) theory that postulates that access to consciousness (from several sensorial modalities) requires transient coordinated activity from associative cortices, in particular the prefrontal cortex and the posterior parietal associative cortex. Several lines of evidence support the view that partial seizures alter consciousness through disturbance of the GW. In particular, a nonlinear relation has been shown between excess of synchronization in the GW regions and the degree of AOC. Changes in thalamocortical synchrony occurring during the spreading of the ictal activity seem particularly involved in the mechanism of altered consciousness. This link between abnormal synchrony and AOC offers new perspectives in the treatment of the AOC since means of decreasing consciousness alteration in seizures could improve patients' quality of life. © 2013.

  6. Global alteration of climate - hopes and fears

    International Nuclear Information System (INIS)

    Viktorov, V.V.

    1992-01-01

    Problems concerning gaseous emission affecting the global climate alteration connected with hotbed effect are considered. Economical and social-political ways of solution of the problem of minimization of gaseous wastes are described. Role of nuclear power plants and alternative power plants in the hotbed effect are analyzed. International cooperation in environmental protection policy is discussed

  7. Different alterations in brain functional networks according to direct and indirect topological connections in patients with schizophrenia.

    Science.gov (United States)

    Park, Chang-Hyun; Lee, Seungyup; Kim, Taewon; Won, Wang Yeon; Lee, Kyoung-Uk

    2017-10-01

    Schizophrenia displays connectivity deficits in the brain, but the literature has shown inconsistent findings about alterations in global efficiency of brain functional networks. We supposed that such inconsistency at the whole brain level may be due to a mixture of different portions of global efficiency at sub-brain levels. Accordingly, we considered measuring portions of global efficiency in two aspects: spatial portions by considering sub-brain networks and topological portions by considering contributions to global efficiency according to direct and indirect topological connections. We proposed adjacency and indirect adjacency as new network parameters attributable to direct and indirect topological connections, respectively, and applied them to graph-theoretical analysis of brain functional networks constructed from resting state fMRI data of 22 patients with schizophrenia and 22 healthy controls. Group differences in the network parameters were observed not for whole brain and hemispheric networks, but for regional networks. Alterations in adjacency and indirect adjacency were in opposite directions, such that adjacency increased, but indirect adjacency decreased in patients with schizophrenia. Furthermore, over connections in frontal and parietal regions, increased adjacency was associated with more severe negative symptoms, while decreased adjacency was associated with more severe positive symptoms of schizophrenia. This finding indicates that connectivity deficits associated with positive and negative symptoms of schizophrenia may involve topologically different paths in the brain. In patients with schizophrenia, although changes in global efficiency may not be clearly shown, different alterations in brain functional networks according to direct and indirect topological connections could be revealed at the regional level. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Pregnancy Complicated by Obesity Induces Global Transcript Expression Alterations in Visceral and Subcutaneous Fat

    Science.gov (United States)

    Bashiri, Asher; Heo, Hye J.; Ben-Avraham, Danny; Mazor, Moshe; Budagov, Temuri; Einstein, Francine H.; Atzmon, Gil

    2014-01-01

    Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet little is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n=4/group) at time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations lead to identification of indolethylamine N-methyltransferase (INMT), tissue factor pathway inhibitor-2 (TFPI-2), and ephrin type-B receptor 6 (EPHB6), not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity. PMID:24696292

  9. Alteration of long-distance functional connectivity and network topology in patients with supratentorial gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji Eun; Kim, Ho Sung; Kim, Sang Joon; Shim, Woo Hyun [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Songpa-Gu, Seoul (Korea, Republic of); Kim, Jeong Hoon [University of Ulsan College of Medicine, Department of Neurosurgery, Asan Medical Center, Seoul (Korea, Republic of)

    2016-03-15

    The need for information regarding functional alterations in patients with brain gliomas is increasing, but little is known about the functional consequences of focal brain tumors throughout the entire brain. Using resting-state functional MR imaging (rs-fMRI), this study assessed functional connectivity in patients with supratentorial brain gliomas with possible alterations in long-distance connectivity and network topology. Data from 36 patients with supratentorial brain gliomas and 12 healthy subjects were acquired using rs-fMRI. The functional connectivity matrix (FCM) was created using 32 pairs of cortical seeds on Talairach coordinates in each individual subject. Local and distant connectivity were calculated using z-scores in the individual patient's FCM, and the averaged FCM of patients was compared with that of healthy subjects. Weighted network analysis was performed by calculating local efficiency, global efficiency, clustering coefficient, and small-world topology, and compared between patients and healthy controls. When comparing the averaged FCM of patients with that of healthy controls, the patients showed decreased long-distance, inter-hemispheric connectivity (0.32 ± 0.16 in patients vs. 0. 42 ± 0.15 in healthy controls, p = 0.04). In network analysis, patients showed increased local efficiency (p < 0.05), but global efficiency, clustering coefficient, and small-world topology were relatively preserved compared to healthy subjects. Patients with supratentorial brain gliomas showed decreased long-distance connectivity while increased local efficiency and preserved small-world topology. The results of this small case series may provide a better understanding of the alterations of functional connectivity in patients with brain gliomas across the whole brain scale. (orig.)

  10. Exploring patterns of alteration in Alzheimer’s disease brain networks: a combined structural and functional connectomics analysis

    Directory of Open Access Journals (Sweden)

    Fulvia Palesi

    2016-09-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the disconnection syndrome hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks in patients affected by AD and mild cognitive impairment (MCI. However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC. In the default mode network (DMN, that was the most affected, axonal loss and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN, disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN, neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI but also with subcortical alterations (revealed by diffusion MRI that extend beyond the areas primarily damaged by neurodegeneration, towards the support of an emerging concept of AD as a

  11. Visual function alterations in essential tremor: A case report

    Directory of Open Access Journals (Sweden)

    David P. Piñero

    2015-09-01

    Full Text Available Our purpose is to report alterations in contrast sensitivity function (CSF and in the magno, parvo and koniocellular visual pathways by means of a multichannel perimeter in case of an essential tremor (ET. A complete evaluation of the visual function was performed in a 69-year old patient, including the analysis of the chromatic discrimination by the Fansworth–Munsell 100 hue test, the measurement of the CSF by the CSV-1000E test, and the detection of potential alteration patterns in the magno, parvo and koniocellular visual pathways by means of a multichannel perimeter. Visual acuity and intraocular pressure (IOP were within the ranges of normality in both eyes. No abnormalities were detected in the fundoscopic examination and in the optical coherence tomography (OCT exam. The results of the color vision examination were also within the ranges of normality. A significant decrease in the achromatic CSFs for right eye (RE and left eye (LE was detected for all spatial frequencies. The statistical global values provided by the multichannel perimeter confirms that there were significant absolute sensitivity losses compared to the normal pattern in RE. In the LE, only a statistically significant decrease in sensitivity was detected for the blue-yellow (BY channel. The pattern standard deviation (PSD values obtained in our patient indicated that there were significant localized losses compared to the normality pattern in the achromatic channel of the RE and in the red-green (RG channel of the LE. Some color vision alterations may be present in ET that cannot be detected with conventional color vision tests, such as the FM 100 Hue.

  12. Cold-induced alteration in the global structure of the male sex ...

    Indian Academy of Sciences (India)

    Cold-induced alteration in the global structure of the male sex ... dar et al. 1978). Chromosome preparated from a single pair of salivary glands show extremely puffy and diffuse ..... Akhtar A. 2003 Dosage compensation: an intertwined world of.

  13. Altered resting-state functional connectivity in women with chronic fatigue syndrome.

    Science.gov (United States)

    Kim, Byung-Hoon; Namkoong, Kee; Kim, Jae-Jin; Lee, Seojung; Yoon, Kang Joon; Choi, Moonjong; Jung, Young-Chul

    2015-12-30

    The biological underpinnings of the psychological factors characterizing chronic fatigue syndrome (CFS) have not been extensively studied. Our aim was to evaluate alterations of resting-state functional connectivity in CFS patients. Participants comprised 18 women with CFS and 18 age-matched female healthy controls who were recruited from the local community. Structural and functional magnetic resonance images were acquired during a 6-min passive-viewing block scan. Posterior cingulate cortex seeded resting-state functional connectivity was evaluated, and correlation analyses of connectivity strength were performed. Graph theory analysis of 90 nodes of the brain was conducted to compare the global and local efficiency of connectivity networks in CFS patients with that in healthy controls. The posterior cingulate cortex in CFS patients showed increased resting-state functional connectivity with the dorsal and rostral anterior cingulate cortex. Connectivity strength of the posterior cingulate cortex to the dorsal anterior cingulate cortex significantly correlated with the Chalder Fatigue Scale score, while the Beck Depression Inventory (BDI) score was controlled. Connectivity strength to the rostral anterior cingulate cortex significantly correlated with the Chalder Fatigue Scale score. Global efficiency of the posterior cingulate cortex was significantly lower in CFS patients, while local efficiency showed no difference from findings in healthy controls. The findings suggest that CFS patients show inefficient increments in resting-state functional connectivity that are linked to the psychological factors observed in the syndrome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Characterizing genomic alterations in cancer by complementary functional associations.

    Science.gov (United States)

    Kim, Jong Wook; Botvinnik, Olga B; Abudayyeh, Omar; Birger, Chet; Rosenbluh, Joseph; Shrestha, Yashaswi; Abazeed, Mohamed E; Hammerman, Peter S; DiCara, Daniel; Konieczkowski, David J; Johannessen, Cory M; Liberzon, Arthur; Alizad-Rahvar, Amir Reza; Alexe, Gabriela; Aguirre, Andrew; Ghandi, Mahmoud; Greulich, Heidi; Vazquez, Francisca; Weir, Barbara A; Van Allen, Eliezer M; Tsherniak, Aviad; Shao, Diane D; Zack, Travis I; Noble, Michael; Getz, Gad; Beroukhim, Rameen; Garraway, Levi A; Ardakani, Masoud; Romualdi, Chiara; Sales, Gabriele; Barbie, David A; Boehm, Jesse S; Hahn, William C; Mesirov, Jill P; Tamayo, Pablo

    2016-05-01

    Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes.

  15. Are there links between responses of soil microbes and ecosystem functioning to elevated CO2, N deposition and warming? A global perspective

    NARCIS (Netherlands)

    Garcia-Palacios, Pablo; Vandegehuchte, Martijn L.; Shaw, E. Ashley; Dam, Marie; Post, Keith H.; Ramirez, Kelly S.; Sylvain, Zachary A.; de Tomasel, Cecilia Milano; Wall, Diana H.

    2015-01-01

    In recent years, there has been an increase in research to understand how global changes' impacts on soil biota translate into altered ecosystem functioning. However, results vary between global change effects, soil taxa, and ecosystem processes studied, and a synthesis of relationships is lacking.

  16. Amelioration of cognitive, motor and endogenous defense functions with silymarin, piracetam and protocatechuic acid in the cerebral global ischemic rat model.

    Science.gov (United States)

    Muley, Milind M; Thakare, Vishnu N; Patil, Rajesh R; Bafna, Pallavi A; Naik, Suresh R

    2013-07-19

    The neuroprotective activities of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) on cerebral global ischemic/reperfusion were evaluated in a rat model. A midline ventral incision was made in the throat region. The right and left common carotid arteries were located and a bilateral common carotid artery occlusion (BCCAO) was performed for 30min using atraumatic clamps followed by a 24h period of reperfusion. Neurological/behavioral functions (cognitive and motor), endogenous defense systems (lipid peroxidation, glutathione, catalase, and superoxide dismutase), reduced water content and infarct size and histopathological alterations were then studied. Silymarin and PCA treatments significantly improved cognitive, motor and endogenous defense functions, histopathological alterations, and, reduced both water content and infarct size compared to the vehicle-treated ischemic control group. Piracetam treatment improved neurological and histopathological alterations, reduced water content and infarct size, but failed to restore/prevent the impaired endogenous defense functions significantly. Silymarin showed better neuroprotection than piracetam and PCA in experimentally induced global ischemic/reperfusion and was able to facilitate mnemonic performance. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Altered resting brain function and structure in professional badminton players.

    Science.gov (United States)

    Di, Xin; Zhu, Senhua; Jin, Hua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan; Rao, Hengyi

    2012-01-01

    Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills.

  18. Longstanding Hyperthyroidism Is Associated with Normal or Enhanced Intrinsic Cardiomyocyte Function despite Decline in Global Cardiac Function

    Science.gov (United States)

    Redetzke, Rebecca A.; Gerdes, A. Martin

    2012-01-01

    Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH). LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function. PMID:23056390

  19. Longstanding hyperthyroidism is associated with normal or enhanced intrinsic cardiomyocyte function despite decline in global cardiac function.

    Directory of Open Access Journals (Sweden)

    Nathan Y Weltman

    Full Text Available Thyroid hormones (THs play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH. LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function.

  20. Are there links between responses of soil microbes and ecosystem functioning to elevated CO2, N deposition and warming? A global perspective.

    Science.gov (United States)

    García-Palacios, Pablo; Vandegehuchte, Martijn L; Shaw, E Ashley; Dam, Marie; Post, Keith H; Ramirez, Kelly S; Sylvain, Zachary A; de Tomasel, Cecilia Milano; Wall, Diana H

    2015-04-01

    In recent years, there has been an increase in research to understand how global changes' impacts on soil biota translate into altered ecosystem functioning. However, results vary between global change effects, soil taxa, and ecosystem processes studied, and a synthesis of relationships is lacking. Therefore, here we initiate such a synthesis to assess whether the effect size of global change drivers (elevated CO2, N deposition, and warming) on soil microbial abundance is related with the effect size of these drivers on ecosystem functioning (plant biomass, soil C cycle, and soil N cycle) using meta-analysis and structural equation modeling. For N deposition and warming, the global change effect size on soil microbes was positively associated with the global change effect size on ecosystem functioning, and these relationships were consistent across taxa and ecosystem processes. However, for elevated CO2, such links were more taxon and ecosystem process specific. For example, fungal abundance responses to elevated CO2 were positively correlated with those of plant biomass but negatively with those of the N cycle. Our results go beyond previous assessments of the sensitivity of soil microbes and ecosystem processes to global change, and demonstrate the existence of general links between the responses of soil microbial abundance and ecosystem functioning. Further we identify critical areas for future research, specifically altered precipitation, soil fauna, soil community composition, and litter decomposition, that are need to better quantify the ecosystem consequences of global change impacts on soil biodiversity. © 2014 John Wiley & Sons Ltd.

  1. Long-duration transcutaneous electric acupoint stimulation alters small-world brain functional networks.

    Science.gov (United States)

    Zhang, Yue; Jiang, Yin; Glielmi, Christopher B; Li, Longchuan; Hu, Xiaoping; Wang, Xiaoying; Han, Jisheng; Zhang, Jue; Cui, Cailian; Fang, Jing

    2013-09-01

    Acupuncture, which is recognized as an alternative and complementary treatment in Western medicine, has long shown efficiencies in chronic pain relief, drug addiction treatment, stroke rehabilitation and other clinical practices. The neural mechanism underlying acupuncture, however, is still unclear. Many studies have focused on the sustained effects of acupuncture on healthy subjects, yet there are very few on the topological organization of functional networks in the whole brain in response to long-duration acupuncture (longer than 20 min). This paper presents a novel study on the effects of long-duration transcutaneous electric acupoint stimulation (TEAS) on the small-world properties of brain functional networks. Functional magnetic resonance imaging was used to construct brain functional networks of 18 healthy subjects (9 males and 9 females) during the resting state. All subjects received both TEAS and minimal TEAS (MTEAS) and were scanned before and after each stimulation. An altered functional network was found with lower local efficiency and no significant change in global efficiency for healthy subjects after TEAS, while no significant difference was observed after MTEAS. The experiments also showed that the nodal efficiencies in several paralimbic/limbic regions were altered by TEAS, and those in middle frontal gyrus and other regions by MTEAS. To remove the psychological effects and the baseline, we compared the difference between diffTEAS (difference between after and before TEAS) and diffMTEAS (difference between after and before MTEAS). The results showed that the local efficiency was decreased and that the nodal efficiencies in frontal gyrus, orbitofrontal cortex, anterior cingulate gyrus and hippocampus gyrus were changed. Based on those observations, we conclude that long-duration TEAS may modulate the short-range connections of brain functional networks and also the limbic system. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Chronic zinc deficiency alters chick gut microbiota composition and function

    Science.gov (United States)

    Zinc (Zn) deficiency is a prevalent micronutrient insufficiency. Although the gut is a vital organ for Zn utilization, and Zn deficiency is associated with impaired intestinal permeability and a global decrease in gastrointestinal health, alterations in the gut microbial ecology of the host under co...

  3. Altered intrinsic functional brain architecture in female patients with bulimia nervosa.

    Science.gov (United States)

    Wang, Li; Kong, Qing-Mei; Li, Ke; Li, Xue-Ni; Zeng, Ya-Wei; Chen, Chao; Qian, Ying; Feng, Shi-Jie; Li, Ji-Tao; Su, Yun'Ai; Correll, Christoph U; Mitchell, Philip B; Yan, Chao-Gan; Zhang, Da-Rong; Si, Tian-Mei

    2017-11-01

    Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large-scale distributed brain regions. These abnormalities

  4. Violent Video Games Alter Brain Function in Young Men

    Science.gov (United States)

    ... feed News from the RSNA Annual Meeting Violent Video Games Alter Brain Function in Young Men At A ... functional MRI, researchers have found that playing violent video games for one week causes changes in brain function. ...

  5. Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.

    Science.gov (United States)

    Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

    2014-02-01

    Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

  6. When "altering brain function" becomes "mind control".

    Science.gov (United States)

    Koivuniemi, Andrew; Otto, Kevin

    2014-01-01

    Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control.

  7. UBC-Nepal expedition: The use of oral antioxidants does not alter cerebrovascular function at sea level or high altitude.

    Science.gov (United States)

    Hansen, Alexander B; Hoiland, Ryan L; Lewis, Nia C S; Tymko, Michael M; Tremblay, Joshua C; Stembridge, Michael; Nowak-Flück, Daniela; Carter, Howard H; Bailey, Damian M; Ainslie, Philip N

    2018-04-01

    What is the central question of the study? Does the use of antioxidants alter cerebrovascular function and blood flow at sea level (344 m) and/or high altitude (5050 m)? What is the main finding and its importance? This is the first study to investigate whether antioxidant administration alters cerebrovascular regulation and blood flow in response to hypercapnia, acute hypoxia and chronic hypoxia in healthy humans. We demonstrate that an acute dose of antioxidants does not alter cerebrovascular function and blood flow at sea level (344 m) or after 12 days at high altitude (5050 m). Hypoxia is associated with an increase in systemic and cerebral formation of free radicals and associated reactants that may be linked to impaired cerebral vascular function and neurological sequelae. To what extent oral antioxidant prophylaxis impacts cerebrovascular function in humans throughout the course of acclimatization to the hypoxia of terrestrial high altitude has not been examined. Thus, the purpose of the present study was to examine the influence of orally ingested antioxidants at clinically relevant doses (vitamins C and E and α-lipoic acid) on cerebrovascular regulation at sea level (344 m; n = 12; female n = 2 participants) and at high altitude (5050 m; n = 9; female n = 2) in a randomized, placebo-controlled and double-blinded crossover design. Hypercapnic and hypoxic cerebrovascular reactivity tests of the internal carotid artery (ICA) were conducted at sea level, and global and regional cerebral blood flow (CBF; i.e. ICA and vertebral artery) were assessed 10-12 days after arrival at 5050 m. At sea level, acute administration of antioxidants did not alter cerebral hypoxic cerebrovascular reactivity (pre versus post: 1.5 ± 0.7 versus 1.2 ± 0.8%∆CBF/-%∆SpO2; P = 0.96) or cerebral hypercapnic cerebrovascular reactivity (pre versus post: 5.7 ± 2.0 versus 5.8 ± 1.9%∆CBF/∆mmHg; P = 0.33). Furthermore, global CBF (P = 0.43) and

  8. Local and Global Function Model of the Liver

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hesheng, E-mail: hesheng@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Feng, Mary [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Jackson, Andrew [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Ten Haken, Randall K.; Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States)

    2016-01-01

    Purpose: To develop a local and global function model in the liver based on regional and organ function measurements to support individualized adaptive radiation therapy (RT). Methods and Materials: A local and global model for liver function was developed to include both functional volume and the effect of functional variation of subunits. Adopting the assumption of parallel architecture in the liver, the global function was composed of a sum of local function probabilities of subunits, varying between 0 and 1. The model was fit to 59 datasets of liver regional and organ function measures from 23 patients obtained before, during, and 1 month after RT. The local function probabilities of subunits were modeled by a sigmoid function in relating to MRI-derived portal venous perfusion values. The global function was fitted to a logarithm of an indocyanine green retention rate at 15 minutes (an overall liver function measure). Cross-validation was performed by leave-m-out tests. The model was further evaluated by fitting to the data divided according to whether the patients had hepatocellular carcinoma (HCC) or not. Results: The liver function model showed that (1) a perfusion value of 68.6 mL/(100 g · min) yielded a local function probability of 0.5; (2) the probability reached 0.9 at a perfusion value of 98 mL/(100 g · min); and (3) at a probability of 0.03 [corresponding perfusion of 38 mL/(100 g · min)] or lower, the contribution to global function was lost. Cross-validations showed that the model parameters were stable. The model fitted to the data from the patients with HCC indicated that the same amount of portal venous perfusion was translated into less local function probability than in the patients with non-HCC tumors. Conclusions: The developed liver function model could provide a means to better assess individual and regional dose-responses of hepatic functions, and provide guidance for individualized treatment planning of RT.

  9. Network analysis of genomic alteration profiles reveals co-altered functional modules and driver genes for glioblastoma.

    Science.gov (United States)

    Gu, Yunyan; Wang, Hongwei; Qin, Yao; Zhang, Yujing; Zhao, Wenyuan; Qi, Lishuang; Zhang, Yuannv; Wang, Chenguang; Guo, Zheng

    2013-03-01

    The heterogeneity of genetic alterations in human cancer genomes presents a major challenge to advancing our understanding of cancer mechanisms and identifying cancer driver genes. To tackle this heterogeneity problem, many approaches have been proposed to investigate genetic alterations and predict driver genes at the individual pathway level. However, most of these approaches ignore the correlation of alteration events between pathways and miss many genes with rare alterations collectively contributing to carcinogenesis. Here, we devise a network-based approach to capture the cooperative functional modules hidden in genome-wide somatic mutation and copy number alteration profiles of glioblastoma (GBM) from The Cancer Genome Atlas (TCGA), where a module is a set of altered genes with dense interactions in the protein interaction network. We identify 7 pairs of significantly co-altered modules that involve the main pathways known to be altered in GBM (TP53, RB and RTK signaling pathways) and highlight the striking co-occurring alterations among these GBM pathways. By taking into account the non-random correlation of gene alterations, the property of co-alteration could distinguish oncogenic modules that contain driver genes involved in the progression of GBM. The collaboration among cancer pathways suggests that the redundant models and aggravating models could shed new light on the potential mechanisms during carcinogenesis and provide new indications for the design of cancer therapeutic strategies.

  10. Altered structure-function relations of semantic processing in youths with high-functioning autism: a combined diffusion and functional MRI study.

    Science.gov (United States)

    Lo, Yu-Chun; Chou, Tai-Li; Fan, Li-Ying; Gau, Susan Shur-Fen; Chiu, Yen-Nan; Tseng, Wen-Yih Isaac

    2013-12-01

    Deficits in language and communication are among the core symptoms of autism, a common neurodevelopmental disorder with long-term impairment. Despite the striking nature of the autistic language impairment, knowledge about its corresponding alterations in the brain is still evolving. We hypothesized that the dual stream language network is altered in autism, and that this alteration could be revealed by changes in the relationships between microstructural integrity and functional activation. The study recruited 20 right-handed male youths with autism and 20 carefully matched individually, typically developing (TD) youths. Microstructural integrity of the left dorsal and left ventral pathways responsible for language processing and the functional activation of the connected brain regions were investigated by using diffusion spectrum imaging and functional magnetic resonance imaging of a semantic task, respectively. Youths with autism had significantly poorer language function, and lower functional activation in left dorsal and left ventral regions of the language network, compared with TD youths. The TD group showed a significant correlation of the functional activation of the left dorsal region with microstructural integrity of the left ventral pathway, whereas the autism group showed a significant correlation of the functional activation of the left ventral region with microstructural integrity of the left dorsal pathway, and moreover verbal comprehension index was correlated with microstructural integrity of the left ventral pathway. These altered structure-function relationships in autism suggest possible involvement of the dual pathways in supporting deficient semantic processing. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

  11. Tumor-altered dendritic cell function: implications for anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Kristian Michael Hargadon

    2013-07-01

    Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti

  12. Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function

    NARCIS (Netherlands)

    Ingólfsson, Helgi I; Thakur, Pratima; Herold, Karl F; Hobart, E Ashley; Ramsey, Nicole B; Periole, Xavier; de Jong, Djurre H; Zwama, Martijn; Yilmaz, Duygu; Hall, Katherine; Maretzky, Thorsten; Hemmings, Hugh C; Blobel, Carl; Marrink, Siewert J; Kocer, Armagan; Sack, Jon T; Andersen, Olaf S

    A wide variety of phytochemicals are consumed for their perceived health benefits. Many of these phytochemicals have been found to alter numerous cell functions, but the mechanisms underlying their biological activity tend to be poorly understood. Phenolic phytochemicals are particularly promiscuous

  13. Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function

    NARCIS (Netherlands)

    Ingólfsson, Helgi I; Thakur, Pratima; Herold, Karl F; Hobart, E Ashley; Ramsey, Nicole B; Periole, Xavier; de Jong, Djurre H; Zwama, Martijn; Yilmaz, Duygu; Hall, Katherine; Maretzky, Thorsten; Hemmings, Hugh C; Blobel, Carl; Marrink, Siewert J; Kocer, Armagan; Sack, Jon T; Andersen, Olaf S

    2014-01-01

    A wide variety of phytochemicals are consumed for their perceived health benefits. Many of these phytochemicals have been found to alter numerous cell functions, but the mechanisms underlying their biological activity tend to be poorly understood. Phenolic phytochemicals are particularly promiscuous

  14. PCBs Alter Dopamine Mediated Function in Aging Workers

    Science.gov (United States)

    2011-01-01

    PCBs Alter Dopamine Mediated Function in Aging Workers 5a. CONTRACT NUMBER 5b. GRANT NUMBER DAMD17-02-1-0173 5c. PROGRAM ELEMENT...hypothesized that occupational exposure to polychlorinated biphenyls (PCBs) reduces dopamine (DA) terminal densities in the basal ganglia. We found...motor function in women compared to similarly aged men with similar bone lead levels. These latter findings are the first to demonstrate a sexual

  15. Prenatal stress alters amygdala functional connectivity in preterm neonates.

    Science.gov (United States)

    Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

    2016-01-01

    Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

  16. Connectomics and neuroticism : an altered functional network organization

    NARCIS (Netherlands)

    Servaas, Michelle N; Geerligs, Linda; Renken, Remco J; Marsman, Jan-Bernard; Ormel, Johan; Riese, Harriëtte; Aleman, André

    The personality trait neuroticism is a potent risk marker for psychopathology. Although the neurobiological basis remains unclear, studies have suggested that alterations in connectivity may underlie it. Therefore, the aim of the current study was to shed more light on the functional network

  17. Parasite-altered feeding behavior in insects: integrating functional and mechanistic research frontiers.

    Science.gov (United States)

    Bernardo, Melissa A; Singer, Michael S

    2017-08-15

    Research on parasite-altered feeding behavior in insects is contributing to an emerging literature that considers possible adaptive consequences of altered feeding behavior for the host or the parasite. Several recent ecoimmunological studies show that insects can adaptively alter their foraging behavior in response to parasitism. Another body of recent work shows that infection by parasites can change the behavior of insect hosts to benefit the parasite; manipulations of host feeding behavior may be part of this phenomenon. Here, we address both the functional and the underlying physiological frontiers of parasite-altered feeding behavior in order to spur research that better integrates the two. Functional categories of parasite-altered behavior that are adaptive for the host include prophylaxis, therapy and compensation, while host manipulation is adaptive for the parasite. To better understand and distinguish prophylaxis, therapy and compensation, further study of physiological feedbacks affecting host sensory systems is especially needed. For host manipulation in particular, research on mechanisms by which parasites control host feedbacks will be important to integrate with functional approaches. We see this integration as critical to advancing the field of parasite-altered feeding behavior, which may be common in insects and consequential for human and environmental health. © 2017. Published by The Company of Biologists Ltd.

  18. Phytochemicals perturb membranes and promiscuously alter protein function.

    Science.gov (United States)

    Ingólfsson, Helgi I; Thakur, Pratima; Herold, Karl F; Hobart, E Ashley; Ramsey, Nicole B; Periole, Xavier; de Jong, Djurre H; Zwama, Martijn; Yilmaz, Duygu; Hall, Katherine; Maretzky, Thorsten; Hemmings, Hugh C; Blobel, Carl; Marrink, Siewert J; Koçer, Armağan; Sack, Jon T; Andersen, Olaf S

    2014-08-15

    A wide variety of phytochemicals are consumed for their perceived health benefits. Many of these phytochemicals have been found to alter numerous cell functions, but the mechanisms underlying their biological activity tend to be poorly understood. Phenolic phytochemicals are particularly promiscuous modifiers of membrane protein function, suggesting that some of their actions may be due to a common, membrane bilayer-mediated mechanism. To test whether bilayer perturbation may underlie this diversity of actions, we examined five bioactive phenols reported to have medicinal value: capsaicin from chili peppers, curcumin from turmeric, EGCG from green tea, genistein from soybeans, and resveratrol from grapes. We find that each of these widely consumed phytochemicals alters lipid bilayer properties and the function of diverse membrane proteins. Molecular dynamics simulations show that these phytochemicals modify bilayer properties by localizing to the bilayer/solution interface. Bilayer-modifying propensity was verified using a gramicidin-based assay, and indiscriminate modulation of membrane protein function was demonstrated using four proteins: membrane-anchored metalloproteases, mechanosensitive ion channels, and voltage-dependent potassium and sodium channels. Each protein exhibited similar responses to multiple phytochemicals, consistent with a common, bilayer-mediated mechanism. Our results suggest that many effects of amphiphilic phytochemicals are due to cell membrane perturbations, rather than specific protein binding.

  19. A comparison of chemical compositions of reported altered oceanic crusts and global MORB data set: implication for isotopic heterogeneity of recycled materials

    Science.gov (United States)

    Shimoda, G.; Kogiso, T.

    2017-12-01

    Chemical composition of altered oceanic crust is one of important constraints to delineate chemical heterogeneity of the mantle. Accordingly, many researchers have been studied to determine bulk chemical composition of altered oceanic crust mainly based on chemical compositions of old oceanic crusts at Site 801 and Site 417/418, and young crust at Site 504 (e.g., Staudigel et al., 1996; Bach et al. 2003; Kuo et al., 2016). Their careful estimation provided reliable bulk chemical compositions of these Sites and revealed common geochemical feature of alteration. To assess effect of recycling of altered oceanic crust on chemical evolution of the mantle, it might be meaningful to discuss whether the reported chemical compositions of altered oceanic crusts can represent chemical composition of globally subducted oceanic crusts. Reported chemical compositions of fresh glass or less altered samples from Site 801, 417/418 and 504 were highly depleted compared to that of global MORB reported by Gale et al. (2013), suggesting that there might be sampling bias. Hence, it could be important to consider chemical difference between oceanic crusts of these three Sites and global MORB to discuss effect of recycling of oceanic crust on isotopic heterogeneity of the mantle. It has been suggested that one of controlling factors of chemical variation of oceanic crust is crustal spreading rate because different degree of partial melting affects chemical composition of magmas produced at a mid-ocean ridge. Crustal spreading rate could also affect intensity of alteration. Namely, oceanic crusts produced at slow-spreading ridges may prone to be altered due to existence of larger displacement faults compared to fast spreading ridges which have relatively smooth topography. Thus, it might be significant to evaluate isotopic evolution of oceanic crusts those were produced at different spreading rates. In this presentation, we will provide a possible chemical variation of altered oceanic

  20. Longitudinal Structural and Functional Brain Network Alterations in a Mouse Model of Neuropathic Pain.

    Science.gov (United States)

    Bilbao, Ainhoa; Falfán-Melgoza, Claudia; Leixner, Sarah; Becker, Robert; Singaravelu, Sathish Kumar; Sack, Markus; Sartorius, Alexander; Spanagel, Rainer; Weber-Fahr, Wolfgang

    2018-04-22

    Neuropathic pain affects multiple brain functions, including motivational processing. However, little is known about the structural and functional brain changes involved in the transition from an acute to a chronic pain state. Here we combined behavioral phenotyping of pain thresholds with multimodal neuroimaging to longitudinally monitor changes in brain metabolism, structure and connectivity using the spared nerve injury (SNI) mouse model of chronic neuropathic pain. We investigated stimulus-evoked pain responses prior to SNI surgery, and one and twelve weeks following surgery. A progressive development and potentiation of stimulus-evoked pain responses (cold and mechanical allodynia) were detected during the course of pain chronification. Voxel-based morphometry demonstrated striking decreases in volume following pain induction in all brain sites assessed - an effect that reversed over time. Similarly, all global and local network changes that occurred following pain induction disappeared over time, with two notable exceptions: the nucleus accumbens, which played a more dominant role in the global network in a chronic pain state and the prefrontal cortex and hippocampus, which showed lower connectivity. These changes in connectivity were accompanied by enhanced glutamate levels in the hippocampus, but not in the prefrontal cortex. We suggest that hippocampal hyperexcitability may contribute to alterations in synaptic plasticity within the nucleus accumbens, and to pain chronification. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Determination of global heart function parameters

    International Nuclear Information System (INIS)

    Adam, W.E.; Hoffmann, H.; Sigel, H.; Bitter, F.; Nechwatal, W.; Stauch, M.; Ulm Univ.; Freiburg Univ.

    1980-01-01

    1. ECG-triggered scintigraphy of the interior of the heart (radioactive ventriculography) is a reliable non-invasive technique for the acquisition of the global and regional function of the left ventricle. 2. The most important global parameter is the output function (OF) of the left ventricle. It can be measured exactly. The decrease of the OF under load is typical for coronary insufficience under load, but is not specifically. 3. A movement disturbance on the ground of a KHK is recognized with highest sensitivity at the decrease of the maximum relaxation velocity of the global left-ventricular time-activity characteristic (fast phase of filling). 4. Regional wall movement disturbances can be measured quantitatively by means of viewing the radioactive nucleid ventriculogramm at the display. 5. The quantitative measurement of the regional function needs an extensive analysis of the local time-activity characteristics of a representative coronary cycle. For this the amplitude and phase and the contraction and relaxation velocity of all time-activity characteristics is determined by Fourier analysis and their spatial distribution is drawn (parametric scan). 6. The parametric scans (distribution of amplitude, phase, contraction and relaxation velocities) describe the regional wall movement in detail, the reliability of its quantitative acquisition has to be approved by further investigations. (orig.) [de

  2. Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

    Science.gov (United States)

    Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

    2016-01-01

    Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

  3. Altered global gene expression profiles in human gastrointestinal epithelial Caco2 cells exposed to nanosilver

    Directory of Open Access Journals (Sweden)

    Saura C. Sahu

    Full Text Available Extensive consumer exposure to food- and cosmetics-related consumer products containing nanosilver is of public safety concern. Therefore, there is a need for suitable in vitro models and sensitive predictive rapid screening methods to assess their toxicity. Toxicogenomic profile showing subtle changes in gene expressions following nanosilver exposure is a sensitive toxicological endpoint for this purpose. We evaluated the Caco2 cells and global gene expression profiles as tools for predictive rapid toxicity screening of nanosilver. We evaluated and compared the gene expression profiles of Caco-2 cells exposed to 20 nm and 50 nm nanosilver at a concentration 2.5 μg/ml. The global gene expression analysis of Caco2 cells exposed to 20 nm nanosilver showed that a total of 93 genes were altered at 4 h exposure, out of which 90 genes were up-regulated and 3 genes were down-regulated. The 24 h exposure of 20 nm silver altered 15 genes in Caco2 cells, out of which 14 were up-regulated and one was down-regulated. The most pronounced changes in gene expression were detected at 4 h. The greater size (50 nm nanosilver at 4 h exposure altered more genes by more different pathways than the smaller (20 nm one. Metallothioneins and heat shock proteins were highly up-regulated as a result of exposure to both the nanosilvers. The cellular pathways affected by the nanosilver exposure is likely to lead to increased toxicity. The results of our study presented here suggest that the toxicogenomic characterization of Caco2 cells is a valuable in vitro tool for assessing toxicity of nanomaterials such as nanosilver. Keywords: Nanosilver, Silver nanoparticles, Nanoparticles, Toxicogenomics, DNA microarray, Global gene expression profiles, Caco2 cells

  4. Altered resting state brain networks in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Martin Göttlich

    Full Text Available Parkinson's disease (PD is a neurodegenerative disorder affecting dopaminergic neurons in the substantia nigra leading to dysfunctional cortico-striato-thalamic-cortical loops. In addition to the characteristic motor symptoms, PD patients often show cognitive impairments, affective changes and other non-motor symptoms, suggesting system-wide effects on brain function. Here, we used functional magnetic resonance imaging and graph-theory based analysis methods to investigate altered whole-brain intrinsic functional connectivity in PD patients (n = 37 compared to healthy controls (n = 20. Global network properties indicated less efficient processing in PD. Analysis of brain network modules pointed to increased connectivity within the sensorimotor network, but decreased interaction of the visual network with other brain modules. We found lower connectivity mainly between the cuneus and the ventral caudate, medial orbitofrontal cortex and the temporal lobe. To identify regions of altered connectivity, we mapped the degree of intrinsic functional connectivity both on ROI- and on voxel-level across the brain. Compared to healthy controls, PD patients showed lower connectedness in the medial and middle orbitofrontal cortex. The degree of connectivity was also decreased in the occipital lobe (cuneus and calcarine, but increased in the superior parietal cortex, posterior cingulate gyrus, supramarginal gyrus and supplementary motor area. Our results on global network and module properties indicated that PD manifests as a disconnection syndrome. This was most apparent in the visual network module. The higher connectedness within the sensorimotor module in PD patients may be related to compensation mechanism in order to overcome the functional deficit of the striato-cortical motor loops or to loss of mutual inhibition between brain networks. Abnormal connectivity in the visual network may be related to adaptation and compensation processes as a consequence

  5. Global spacetime symmetries in the functional Schroedinger picture

    International Nuclear Information System (INIS)

    Halliwell, J.J.

    1991-01-01

    In the conventional functional Schroedinger quantization of field theory, the background spacetime manifold is foliated into a set of three-surfaces and the quantum state of the field is represented by a wave functional of the field configurations on each three-surface. Although this procedure may be covariantly described, the wave functionals generally fail to carry a representation of the complete spacetime symmetry group of the background, such as the Poincare group in Minkowski spacetime, because spacetime symmetries generally involve distortions or motions of the three-surfaces themselves within that spacetime. In this paper, we show that global spacetime symmetries in the functional Schroedinger picture may be represented by parametrizing the field theory---raising to the status of dynamical variables the embedding variables describing the spacetime location of each three-surface. In particular, we show that the embedding variables provide a connection between the purely geometrical operation of an isometry group on the spacetime and the operation of the usual global symmetry generators (constructed from the energy-momentum tensor) on the wave functionals of the theory. We study the path-integral representation of the wave functionals of the parametrized field theory. We show how to construct, from the path integral, wave functionals that are annihilated by the global symmetry generators, i.e., that are invariant under global spacetime symmetry groups. The invariance of the class of histories summed over in the path integral is identified as the source of the invariance of the wave functionals. We apply this understanding to a study of vacuum states in the de Sitter spacetime. We make mathematically precise a previously given heuristic argument for the de Sitter invariance of the matter wave functionals defined by the no-boundary proposal of Hartle and Hawking

  6. Altered functional connectivity of interoception in illness anxiety disorder.

    Science.gov (United States)

    Grossi, Dario; Longarzo, Mariachiara; Quarantelli, Mario; Salvatore, Elena; Cavaliere, Carlo; De Luca, Paolofabrizio; Trojano, Luigi; Aiello, Marco

    2017-01-01

    Interoception collects all information coming from the body and is sustained by several brain areas such as insula and cingulate cortex. Here, we used resting-state functional magnetic resonance imaging to investigate functional connectivity (FC) of networks implied in interoception in patients with Illness anxiety disorders (IADs). We observed significantly reduced FC between the left extrastriate body area (EBA) and the paracentral lobule compared to healthy controls. Moreover, the correlation analysis between behavioural questionnaires and ROI to ROI FC showed that higher levels of illness anxiety were related to hyper-connectivity between EBA and amygdala and hippocampus. Scores on a questionnaire for interoceptive awareness were significantly correlated with higher FC between right hippocampus and nucleus accumbens bilaterally, and with higher connectivity between left anterior cingulate cortex (ACC) and left orbitofrontal cortex (OFC). Last, patients showed increased interoceptive awareness, measured by Self-Awareness Questionnaire (SAQ), and reduced capability in recognizing emotions, indicating inverse correlation between interoception and emotional awareness. Taken together our results suggested that, in absence of structural and micro-structural changes, patients with IADs show functional alteration in the neural network involved in the self-body representation; such functional alteration might be the target of possible treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. An Evaluation of the Sniffer Global Optimization Algorithm Using Standard Test Functions

    Science.gov (United States)

    Butler, Roger A. R.; Slaminka, Edward E.

    1992-03-01

    The performance of Sniffer—a new global optimization algorithm—is compared with that of Simulated Annealing. Using the number of function evaluations as a measure of efficiency, the new algorithm is shown to be significantly better at finding the global minimum of seven standard test functions. Several of the test functions used have many local minima and very steep walls surrounding the global minimum. Such functions are intended to thwart global minimization algorithms.

  8. Global functioning and disability in dissociative disorders.

    Science.gov (United States)

    Mueller-Pfeiffer, Christoph; Rufibach, Kaspar; Perron, Noelle; Wyss, Daniela; Kuenzler, Cornelia; Prezewowsky, Cornelia; Pitman, Roger K; Rufer, Michael

    2012-12-30

    Dissociative disorders are frequent comorbid conditions of other mental disorders. Yet, there is controversy about their clinical relevance, and little systematic research has been done on how they influence global functioning. Outpatients and day care patients (N=160) of several psychiatric units in Switzerland were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Axis I Disorders, Structured Clinical Interview for DSM-IV Dissociative Disorders, Global Assessment of Functioning Scale, and World Health Organization Disability Assessment Schedule-II. The association between subjects with a dissociative disorder (N=30) and functional impairment after accounting for non-dissociative axis I disorders was evaluated by linear regression models. We found a proportion of 18.8% dissociative disorders (dissociative amnesia=0%, dissociative fugue=0.6%, depersonalization disorder=4.4%, dissociative identity disorder=7.5%, dissociative disorder-not-otherwise-specified=6.3%) across treatment settings. Adjusted for other axis I disorders, subjects with a comorbid dissociative identity disorder or dissociative disorder-not-otherwise-specified had a median global assessment of functioning score that was 0.86 and 0.88 times, respectively, the score of subjects without a comorbid dissociative disorder. These findings support the hypothesis that complex dissociative disorders, i.e., dissociative identity disorder and dissociative disorder-not-otherwise-specified, contribute to functional impairment above and beyond the impact of co-existing non-dissociative axis I disorders, and that they qualify as "serious mental illness". Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Functional diversity of fish in estuaries at a global extent

    Directory of Open Access Journals (Sweden)

    Rita P Vasconcelos

    2015-10-01

    Full Text Available Biodiversity is currently viewed as a framework encompassing multiple facets of the variety of life, including taxonomic and functional aspects. Species richness and composition of fish assemblages in estuaries is defined by global to local processes acting on community colonization. The present study further investigates how biodiversity of fish assemblages varies among estuaries globally, by simultaneously analysing taxonomic and functional richness and diversity of assemblages. A comprehensive worldwide database was compiled on the fish assemblage composition and environmental characteristics of estuaries. In addition, functional attributes of the fish species were characterized such as body size, habitat use and trophic ecology. We investigated the relationship between taxonomic and functional aspects of biodiversity, i.e. the match or mismatch between the two. We also explored how functional diversity of fish assemblages varied among estuaries globally and related to environmental features of estuaries, i.e. historic and contemporary, global and local constraints. The results are explored in the context of ecosystem functioning and resilience, and outcomes relevant to assist in prioritizing conservation efforts are highlighted.

  10. Default Mode Dynamics for Global Functional Integration.

    Science.gov (United States)

    Vatansever, Deniz; Menon, David K; Manktelow, Anne E; Sahakian, Barbara J; Stamatakis, Emmanuel A

    2015-11-18

    The default mode network (DMN) has been traditionally assumed to hinder behavioral performance in externally focused, goal-directed paradigms and to provide no active contribution to human cognition. However, recent evidence suggests greater DMN activity in an array of tasks, especially those that involve self-referential and memory-based processing. Although data that robustly demonstrate a comprehensive functional role for DMN remains relatively scarce, the global workspace framework, which implicates the DMN in global information integration for conscious processing, can potentially provide an explanation for the broad range of higher-order paradigms that report DMN involvement. We used graph theoretical measures to assess the contribution of the DMN to global functional connectivity dynamics in 22 healthy volunteers during an fMRI-based n-back working-memory paradigm with parametric increases in difficulty. Our predominant finding is that brain modularity decreases with greater task demands, thus adapting a more global workspace configuration, in direct relation to increases in reaction times to correct responses. Flexible default mode regions dynamically switch community memberships and display significant changes in their nodal participation coefficient and strength, which may reflect the observed whole-brain changes in functional connectivity architecture. These findings have important implications for our understanding of healthy brain function, as they suggest a central role for the DMN in higher cognitive processing. The default mode network (DMN) has been shown to increase its activity during the absence of external stimulation, and hence was historically assumed to disengage during goal-directed tasks. Recent evidence, however, implicates the DMN in self-referential and memory-based processing. We provide robust evidence for this network's active contribution to working memory by revealing dynamic reconfiguration in its interactions with other networks

  11. Increased Global Interaction Across Functional Brain Modules During Cognitive Emotion Regulation.

    Science.gov (United States)

    Brandl, Felix; Mulej Bratec, Satja; Xie, Xiyao; Wohlschläger, Afra M; Riedl, Valentin; Meng, Chun; Sorg, Christian

    2017-07-13

    Cognitive emotion regulation (CER) enables humans to flexibly modulate their emotions. While local theories of CER neurobiology suggest interactions between specialized local brain circuits underlying CER, e.g., in subparts of amygdala and medial prefrontal cortices (mPFC), global theories hypothesize global interaction increases among larger functional brain modules comprising local circuits. We tested the global CER hypothesis using graph-based whole-brain network analysis of functional MRI data during aversive emotional processing with and without CER. During CER, global between-module interaction across stable functional network modules increased. Global interaction increase was particularly driven by subregions of amygdala and cuneus-nodes of highest nodal participation-that overlapped with CER-specific local activations, and by mPFC and posterior cingulate as relevant connector hubs. Results provide evidence for the global nature of human CER, complementing functional specialization of embedded local brain circuits during successful CER. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Developing empirical collapse fragility functions for global building types

    Science.gov (United States)

    Jaiswal, K.; Wald, D.; D'Ayala, D.

    2011-01-01

    Building collapse is the dominant cause of casualties during earthquakes. In order to better predict human fatalities, the U.S. Geological Survey’s Prompt Assessment of Global Earthquakes for Response (PAGER) program requires collapse fragility functions for global building types. The collapse fragility is expressed as the probability of collapse at discrete levels of the input hazard defined in terms of macroseismic intensity. This article provides a simple procedure for quantifying collapse fragility using vulnerability criteria based on the European Macroseismic Scale (1998) for selected European building types. In addition, the collapse fragility functions are developed for global building types by fitting the beta distribution to the multiple experts’ estimates for the same building type (obtained from EERI’s World Housing Encyclopedia (WHE)-PAGER survey). Finally, using the collapse probability distributions at each shaking intensity level as a prior and field-based collapse-rate observations as likelihood, it is possible to update the collapse fragility functions for global building types using the Bayesian procedure.

  13. Functional alterations of astrocytes in mental disorders: pharmacological significance as a drug target

    Directory of Open Access Journals (Sweden)

    Yutaka eKoyama

    2015-07-01

    Full Text Available Astrocytes play an essential role in supporting brain functions in physiological and pathological states. Modulation of their pathophysiological responses have beneficial actions on nerve tissue injured by brain insults and neurodegenerative diseases, therefore astrocytes are recognized as promising targets for neuroprotective drugs. Recent investigations have identified several astrocytic mechanisms for modulating synaptic transmission and neural plasticity. These include altered expression of transporters for neurotransmitters, release of gliotransmitters and neurotrophic factors, and intercellular communication through gap junctions. Investigation of patients with mental disorders shows morphological and functional alterations in astrocytes. According to these observations, manipulation of astrocytic function by gene mutation and pharmacological tools reproduce mental disorder-like behavior in experimental animals. Some drugs clinically used for mental disorders affect astrocyte function. As experimental evidence shows their role in the pathogenesis of mental disorders, astrocytes have gained much attention as drug targets for mental disorders. In this article, I review functional alterations of astrocytes in several mental disorders including schizophrenia, mood disorder, drug dependence, and neurodevelopmental disorders. The pharmacological significance of astrocytes in mental disorders is also discussed.

  14. Coastal ecosystems on a tipping point: global warming and parasitism combine to alter community structure and function.

    Science.gov (United States)

    Mouritsen, Kim N; Sørensen, Mikkel M; Poulin, Robert; Fredensborg, Brian L

    2018-05-16

    Mounting evidence suggests that the transmission of certain parasites is facilitated by increasing temperatures, causing their host population to decline. However, no study has yet addressed how temperature and parasitism may combine to shape the functional structure of a whole host community in the face of global warming. Here, we apply an outdoor mesocosm approach supported by field surveys to elucidate this question in a diverse intertidal community of amphipods infected by the pathogenic microphallid trematode, Maritrema novaezealandensis. Under present temperature (17°C) and level of parasitism, the parasite had little impact on the host community. However, elevating the temperature to 21°C in presence of parasites induced massive structural changes: amphipod abundances decreased species-specifically, affecting epibenthic species but leaving infaunal species largely untouched. In effect, species diversity dropped significantly. In contrast, 4-degree higher temperatures in absence of parasitism had limited influence on the amphipod community. Further elevating temperatures (19-26°C) and parasitism, simulating a prolonged heat-wave scenario, resulted in an almost complete parasite-induced extermination of the amphipod community at 26°C. In addition, at 19°C, just two degrees above the present average, a similar temperature-parasite synergistic impact on community structure emerged as seen at 21°C under lower parasite pressure. The heat-wave temperature of 26°C per se affected the amphipod community in a comparable way: species diversity declined and the infaunal species were favoured at the expense of epibenthic species. Our experimental findings are corroborated by field data demonstrating a strong negative relationship between current amphipod species richness and the level of Maritrema parasitism across 12 sites. Hence, owing to the synergistic impact of temperature and parasitism, our study predicts that coastal amphipod communities will deteriorate

  15. Exercise alters resting state functional connectivity of motor circuits in Parkinsonian rats

    Science.gov (United States)

    Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I.; Holschneider, Daniel P.

    2014-01-01

    Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson’s disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (a) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (b) emergence of the ventrolateral striatum as a new broadly connected network hub; (c) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the Parkinsonian rats, which could underlie recovery in motor functions observed in these rats. PMID:25219465

  16. ALTER-GLOBALISM AND DEVELOPMENT IN MIGRATION CONDITIONS. THE CASE OF AN EAST EUROPEAN COUNTRY

    OpenAIRE

    Alina HALLER

    2017-01-01

    Globalisation is a process that brings advantages and disadvantages to all states, regardless of their stage of development. The relative deprivation, especially the financial one, of the developing countries is a reason of frustration, which motivates the emigration decision; hence our orientation to alter-globalism. In this paper, I intend to highlight by means of analysis, synthesis, deduction, induction, and statistic data, the causes and types of migration in Romania’s case, one of the m...

  17. Alteration in neonatal nutrition causes perturbations in hypothalamic neural circuits controlling reproductive function.

    Science.gov (United States)

    Caron, Emilie; Ciofi, Philippe; Prevot, Vincent; Bouret, Sebastien G

    2012-08-15

    It is increasingly accepted that alterations of the early life environment may have lasting impacts on physiological functions. In particular, epidemiological and animal studies have indicated that changes in growth and nutrition during childhood and adolescence can impair reproductive function. However, the precise biological mechanisms that underlie these programming effects of neonatal nutrition on reproduction are still poorly understood. Here, we used a mouse model of divergent litter size to investigate the effects of early postnatal overnutrition and undernutrition on the maturation of hypothalamic circuits involved in reproductive function. Neonatally undernourished females display attenuated postnatal growth associated with delayed puberty and defective development of axonal projections from the arcuate nucleus to the preoptic region. These alterations persist into adulthood and specifically affect the organization of neural projections containing kisspeptin, a key neuropeptide involved in pubertal activation and fertility. Neonatal overfeeding also perturbs the development of neural projections from the arcuate nucleus to the preoptic region, but it does not result in alterations in kisspeptin projections. These studies indicate that alterations in the early nutritional environment cause lasting and deleterious effects on the organization of neural circuits involved in the control of reproduction, and that these changes are associated with lifelong functional perturbations.

  18. Warming alters energetic structure and function but not resilience of soil food webs

    Science.gov (United States)

    Schwarz, Benjamin; Barnes, Andrew D.; Thakur, Madhav P.; Brose, Ulrich; Ciobanu, Marcel; Reich, Peter B.; Rich, Roy L.; Rosenbaum, Benjamin; Stefanski, Artur; Eisenhauer, Nico

    2017-12-01

    Climate warming is predicted to alter the structure, stability, and functioning of food webs1-5. Yet, despite the importance of soil food webs for energy and nutrient turnover in terrestrial ecosystems, the effects of warming on these food webs—particularly in combination with other global change drivers—are largely unknown. Here, we present results from two complementary field experiments that test the interactive effects of warming with forest canopy disturbance and drought on energy flux in boreal-temperate ecotonal forest soil food webs. The first experiment applied a simultaneous above- and belowground warming treatment (ambient, +1.7 °C, +3.4 °C) to closed-canopy and recently clear-cut forest, simulating common forest disturbance6. The second experiment crossed warming with a summer drought treatment (-40% rainfall) in the clear-cut habitats. We show that warming reduces energy flux to microbes, while forest canopy disturbance and drought facilitates warming-induced increases in energy flux to higher trophic levels and exacerbates the reduction in energy flux to microbes, respectively. Contrary to expectations, we find no change in whole-network resilience to perturbations, but significant losses in ecosystem functioning. Warming thus interacts with forest disturbance and drought, shaping the energetic structure of soil food webs and threatening the provisioning of multiple ecosystem functions in boreal-temperate ecotonal forests.

  19. Global Change Effects on Plant-Soil Interactions

    DEFF Research Database (Denmark)

    Dam, Marie

    of this dissertation has been to determine how soil food web structure and function is affected when the quantity and quality of plant input is altered under global change. By studying the abundance and composition of soil organisms, particularly those in the rhizosphere, closely associated with living plants, we...... (Paper III). Furthermore, by way of meta-analysis, the role of organisms in global change effects on ecosystem function is modelled (Paper IV). Among CO2, warming and summer drought, CO2 is the factor most consistently impacting soil organisms. CO2 increases abundance of microorganisms and nematodes...... suggest that not only the global change effects on established ecosystems, but also the global change effects on plant community composition as well as land use management may determine the composition and function of soil food webs in the future....

  20. miR-155, identified as anti-metastatic by global miRNA profiling of a metastasis model, inhibits cancer cell extravasation and colonization in vivo and causes significant signaling alterations

    DEFF Research Database (Denmark)

    Gravgaard, Karina Hedelund; Terp, Mikkel G; Lund, Rikke R

    2015-01-01

    To gain insight into miRNA regulation in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using global miRNA profiling, 28 miRNAs were found to exhibit significantly altered...... proliferation or apoptosis in established lung tumors. To identify proteins regulated by miR-155 and thus delineate its function in our cell model, we compared the proteome of xenograft tumors derived from miR-155-overexpressing CL16 cells and CL16 control cells using mass spectrometry-based proteomics. >4......,000 proteins were identified, of which 92 were consistently differentially expressed. Network analysis revealed that the altered proteins were associated with cellular functions such as movement, growth and survival as well as cell-to-cell signaling and interaction. Downregulation of the three metastasis...

  1. Assessment of Global Functioning in Adolescents with Autism Spectrum Disorders: Utility of the Developmental Disability-Child Global Assessment Scale

    Science.gov (United States)

    White, Susan W.; Smith, Laura A.; Schry, Amie R.

    2014-01-01

    Assessment of global functioning is an important consideration in treatment outcome research; yet, there is little guidance on its evidence-based assessment for children with autism spectrum disorders. This study investigated the utility and validity of clinician-rated global functioning using the Developmental Disability-Child Global Assessment…

  2. Altered Distant Synchronization of Background Network in Mild Cognitive Impairment during an Executive Function Task

    Directory of Open Access Journals (Sweden)

    Pengyun Wang

    2017-09-01

    Full Text Available Few studies to date have investigated the background network in the cognitive state relying on executive function in mild cognitive impairment (MCI patients. Using the index of degree of centrality (DC, we explored distant synchronization of background network in MCI during a hybrid delayed-match-to-sample task (DMST, which mainly relies on the working memory component of executive function. We observed significant interactions between group and cognitive state in the bilateral posterior cingulate cortex (PCC and the ventral subregion of precuneus. For normal control (NC group, the long distance functional connectivity (FC of the PCC/precuneus with the other regions of the brain was higher in rest state than that working memory state. For MCI patients, however, this pattern altered. There was no significant difference between rest and working memory state. The similar pattern was observed in the other cluster located in the right angular gyrus. To examine whether abnormal DC in PCC/precuneus and angular gyrus partially resulted from the deficit of FC between these regions and the other parts in the whole brain, we conducted a seed-based correlation analysis with these regions as seeds. The results indicated that the FC between bilateral PCC/precuneus and the right inferior parietal lobule (IPL increased from rest to working memory state for NC participants. For MCI patients, however, there was no significant change between rest and working memory state. The similar pattern was observed for the FC between right angular gyrus and right anterior insula. However, there was no difference between MCI and NC groups in global efficiency and modularity. It may indicate a lack of efficient reorganization from rest state to a working memory state in the brain network of MCI patients. The present study demonstrates the altered distant synchronization of background network in MCI during a task relying on executive function. The results provide a new

  3. Supporting women with advanced breast cancer: the impact of altered functional status on their social roles.

    Science.gov (United States)

    Chen, Bai Qi Peggy; Parmar, Monica P; Gartshore, Kimberley

    2014-01-01

    Despite early detection of breast cancer and the progress of treatment modalities, metastasis-specific symptoms continue to impact women's functional status and daily living. The aim of this study was to explore the experience of altered functional status and social roles of women with advanced breast cancer. Using qualitative descriptive methodology, semi-structured interviews were conducted with 10 women diagnosed with advanced breast cancer and altered functional status attending a tertiary care cancer centre. Results illustrated the adaptive experience of women living with their illness as they reshaped their social roles to fit with their altered functional status and advanced disease. These findings highlight the opportunity for supportive care nursing interventions to facilitate the behavioural and cognitive transitions that are experienced by women with advanced breast cancer and altered functional status. These results may have implications for women with other advanced chronic diseases, though more research is required.

  4. Altered cortical hubs in functional brain networks in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ma, Xujing; Zhang, Jiuquan; Zhang, Youxue; Chen, Heng; Li, Rong; Wang, Jian; Chen, Huafu

    2015-11-01

    Cortical hubs are highly connected nodes in functional brain networks that play vital roles in the efficient transfer of information across brain regions. Although altered functional connectivity has been found in amyotrophic lateral sclerosis (ALS), the changing pattern in functional network hubs in ALS remains unknown. In this study, we applied a voxel-wise method to investigate the changing pattern of cortical hubs in ALS. Through resting-state fMRI, we constructed whole-brain voxel-wise functional networks by measuring the temporal correlations of each pair of brain voxels and identified hubs using the graph theory method. Specifically, a functional connectivity strength (FCS) map was derived from the data on 20 patients with ALS and 20 healthy controls. The brain regions with high FCS values were regarded as functional network hubs. Functional hubs were found mainly in the bilateral precuneus, parietal cortex, medial prefrontal cortex, and in several visual regions and temporal areas in both groups. Within the hub regions, the ALS patients exhibited higher FCS in the prefrontal cortex compared with the healthy controls. The FCS value in the significantly abnormal hub regions was correlated with clinical variables. Results indicated the presence of altered cortical hubs in the ALS patients and could therefore shed light on the pathophysiology mechanisms underlying ALS.

  5. Altered attentional control strategies but spared executive functioning in chronic cannabis users.

    Science.gov (United States)

    Nusbaum, Amy T; Whitney, Paul; Cuttler, Carrie; Spradlin, Alexander; Hinson, John M; McLaughlin, Ryan J

    2017-12-01

    Cannabis use has increased rapidly in recent decades. The increase in cannabis use makes it important to understand the potential influence of chronic use on attentional control and other executive functions (EFs). Because cannabis is often used to reduce stress, and because stress can constrain attentional control and EFs, the primary goal of this study was to determine the joint effect of acute stress and chronic cannabis use on specific EFs. Thirty-nine cannabis users and 40 non-users were assigned to either a stress or no stress version of the Maastricht Acute Stress Test. Participants then completed two cognitive tasks that involve EFs: (1) task switching, and (2) a novel Flexible Attentional Control Task. These two tasks provided assessments of vigilant attention, inhibitory control, top-down attentional control, and cognitive flexibility. Salivary cortisol was assessed throughout the study. Reaction time indices showed an interaction between stress and cannabis use on top-down attentional control (p=0.036, n p 2 =0.059). Follow-up tests showed that cannabis users relied less on top-down attentional control than did non-users in the no stress version. Despite not relying on top-down control, the cannabis users showed no overall performance deficits on the tasks. Chronic cannabis users performed cognitive tasks involving EFs as well as non-users while not employing cognitive control processes that are typical for such tasks. These results indicate alterations in cognitive processing in cannabis users, but such alterations do not necessarily lead to global performance deficits. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Alteration and reorganization of functional networks: a new perspective in brain injury study

    Directory of Open Access Journals (Sweden)

    Nazareth P. Castellanos

    2011-09-01

    Full Text Available Plasticity is the mechanism underlying brain’s potential capability to compensate injury. Recently several studies have shown that functional connections among brain areas are severely altered by brain injury and plasticity leading to a reorganization of the networks. This new approach studies the impact of brain injury by means of alteration of functional interactions. The concept of functional connectivity refers to the statistical interdependencies between physiological time series simultaneously recorded in various brain areas and it could be an essential tool for brain function studies, being its deviation from healthy reference an indicator for damage. In this article, we review studies investigating functional connectivity changes after brain injury and subsequent recovery, providing an accessible introduction to common mathematical methods to infer functional connectivity, exploring their capabilities, future perspectives and clinical uses in brain injury studies.

  7. Dissociation and Alterations in Brain Function and Structure: Implications for Borderline Personality Disorder.

    Science.gov (United States)

    Krause-Utz, Annegret; Frost, Rachel; Winter, Dorina; Elzinga, Bernet M

    2017-01-01

    Dissociation involves disruptions of usually integrated functions of consciousness, perception, memory, identity, and affect (e.g., depersonalization, derealization, numbing, amnesia, and analgesia). While the precise neurobiological underpinnings of dissociation remain elusive, neuroimaging studies in disorders, characterized by high dissociation (e.g., depersonalization/derealization disorder (DDD), dissociative identity disorder (DID), dissociative subtype of posttraumatic stress disorder (D-PTSD)), have provided valuable insight into brain alterations possibly underlying dissociation. Neuroimaging studies in borderline personality disorder (BPD), investigating links between altered brain function/structure and dissociation, are still relatively rare. In this article, we provide an overview of neurobiological models of dissociation, primarily based on research in DDD, DID, and D-PTSD. Based on this background, we review recent neuroimaging studies on associations between dissociation and altered brain function and structure in BPD. These studies are discussed in the context of earlier findings regarding methodological differences and limitations and concerning possible implications for future research and the clinical setting.

  8. Autistic and schizotypal traits and global functioning in bipolar I disorder.

    Science.gov (United States)

    Abu-Akel, Ahmad; Clark, Jennifer; Perry, Amy; Wood, Stephen J; Forty, Liz; Craddock, Nick; Jones, Ian; Gordon-Smith, Katherine; Jones, Lisa

    2017-01-01

    To determine the expression of autistic and positive schizotypal traits in a large sample of adults with bipolar I disorder (BD I), and the effect of co-occurring autistic and positive schizotypal traits on global functioning in BD I. Autistic and positive schizotypal traits were self-assessed in 797 individuals with BD-I recruited by the Bipolar Disorder Research Network. Differences in global functioning (rated using the Global Assessment Scale) during lifetime worst depressive and manic episodes (GASD and GASM respectively) were calculated in groups with high/low autistic and positive schizotypal traits. Regression analyses assessed the interactive effect of autistic and positive schizotypal traits on global functioning. 47.2% (CI=43.7-50.7%) showed clinically significant levels of autistic traits, and 23.22% (95% CI=20.29-26.14) showed clinically significant levels of positive schizotypal traits. In the worst episode of mania, the high autistic, high positive schizotypal group had better global functioning compared to the other groups. Individual differences analyses showed that high levels of both traits were associated with better global functioning in both mood states. Autistic and schizotypal traits were assessed using self-rated questionnaires. Expression of autistic and schizotypal traits in adults with BD I is prevalent, and may be important to predict illness aetiology, prognosis, and diagnostic practices in this population. Future work should focus on replicating these findings in independent samples, and on the biological and/or psychosocial mechanisms underlying better global functioning in those who have high levels of both autistic and positive schizotypal traits. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Mixed kernel function support vector regression for global sensitivity analysis

    Science.gov (United States)

    Cheng, Kai; Lu, Zhenzhou; Wei, Yuhao; Shi, Yan; Zhou, Yicheng

    2017-11-01

    Global sensitivity analysis (GSA) plays an important role in exploring the respective effects of input variables on an assigned output response. Amongst the wide sensitivity analyses in literature, the Sobol indices have attracted much attention since they can provide accurate information for most models. In this paper, a mixed kernel function (MKF) based support vector regression (SVR) model is employed to evaluate the Sobol indices at low computational cost. By the proposed derivation, the estimation of the Sobol indices can be obtained by post-processing the coefficients of the SVR meta-model. The MKF is constituted by the orthogonal polynomials kernel function and Gaussian radial basis kernel function, thus the MKF possesses both the global characteristic advantage of the polynomials kernel function and the local characteristic advantage of the Gaussian radial basis kernel function. The proposed approach is suitable for high-dimensional and non-linear problems. Performance of the proposed approach is validated by various analytical functions and compared with the popular polynomial chaos expansion (PCE). Results demonstrate that the proposed approach is an efficient method for global sensitivity analysis.

  10. Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.

    Science.gov (United States)

    Batalle, Dafnis; Muñoz-Moreno, Emma; Tornador, Cristian; Bargallo, Nuria; Deco, Gustavo; Eixarch, Elisenda; Gratacos, Eduard

    2016-04-01

    The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Near-future carbon dioxide levels alter fish behaviour by interfering with neurotransmitter function

    Science.gov (United States)

    Nilsson, Göran E.; Dixson, Danielle L.; Domenici, Paolo; McCormick, Mark I.; Sørensen, Christina; Watson, Sue-Ann; Munday, Philip L.

    2012-03-01

    Predicted future CO2 levels have been found to alter sensory responses and behaviour of marine fishes. Changes include increased boldness and activity, loss of behavioural lateralization, altered auditory preferences and impaired olfactory function. Impaired olfactory function makes larval fish attracted to odours they normally avoid, including ones from predators and unfavourable habitats. These behavioural alterations have significant effects on mortality that may have far-reaching implications for population replenishment, community structure and ecosystem function. However, the underlying mechanism linking high CO2 to these diverse responses has been unknown. Here we show that abnormal olfactory preferences and loss of behavioural lateralization exhibited by two species of larval coral reef fish exposed to high CO2 can be rapidly and effectively reversed by treatment with an antagonist of the GABA-A receptor. GABA-A is a major neurotransmitter receptor in the vertebrate brain. Thus, our results indicate that high CO2 interferes with neurotransmitter function, a hitherto unrecognized threat to marine populations and ecosystems. Given the ubiquity and conserved function of GABA-A receptors, we predict that rising CO2 levels could cause sensory and behavioural impairment in a wide range of marine species, especially those that tightly control their acid-base balance through regulatory changes in HCO3- and Cl- levels.

  12. Altered functional connectivity of the default mode network in Williams syndrome: a multimodal approach.

    Science.gov (United States)

    Sampaio, Adriana; Moreira, Pedro Silva; Osório, Ana; Magalhães, Ricardo; Vasconcelos, Cristiana; Férnandez, Montse; Carracedo, Angel; Alegria, Joana; Gonçalves, Óscar F; Soares, José Miguel

    2016-07-01

    Resting state brain networks are implicated in a variety of relevant brain functions. Importantly, abnormal patterns of functional connectivity (FC) have been reported in several neurodevelopmental disorders. In particular, the Default Mode Network (DMN) has been found to be associated with social cognition. We hypothesize that the DMN may be altered in Williams syndrome (WS), a neurodevelopmental genetic disorder characterized by an unique cognitive and behavioral phenotype. In this study, we assessed the architecture of the DMN using fMRI in WS patients and typically developing matched controls (sex and age) in terms of FC and volumetry of the DMN. Moreover, we complemented the analysis with a functional connectome approach. After excluding participants due to movement artifacts (n = 3), seven participants with WS and their respective matched controls were included in the analyses. A decreased FC between the DMN regions was observed in the WS group when compared with the typically developing group. Specifically, we found a decreased FC in a posterior hub of the DMN including the precuneus, calcarine and the posterior cingulate of the left hemisphere. The functional connectome approach showed a focalized and global increased FC connectome in the WS group. The reduced FC of the posterior hub of the DMN in the WS group is consistent with immaturity of the brain FC patterns and may be associated with the singularity of their visual spatial phenotype. © 2016 John Wiley & Sons Ltd.

  13. Frequency-Dependent Altered Functional Connections of Default Mode Network in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Youjun Li

    2017-08-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder associated with the progressive dysfunction of cognitive ability. Previous research has indicated that the default mode network (DMN is closely related to cognition and is impaired in Alzheimer’s disease. Because recent studies have shown that different frequency bands represent specific physiological functions, DMN functional connectivity studies of the different frequency bands based on resting state fMRI (RS-fMRI data may provide new insight into AD pathophysiology. In this study, we explored the functional connectivity based on well-defined DMN regions of interest (ROIs from the five frequency bands: slow-5 (0.01–0.027 Hz, slow-4 (0.027–0.073 Hz, slow-3 (0.073–0.198 Hz, slow-2 (0.198–0.25 Hzs and standard low-frequency oscillations (LFO (0.01–0.08 Hz. We found that the altered functional connectivity patterns are mainly in the frequency band of slow-5 and slow-4 and that the decreased connections are long distance, but some relatively short connections are increased. In addition, the altered functional connections of the DMN in AD are frequency dependent and differ between the slow-5 and slow-4 bands. Mini-Mental State Examination scores were significantly correlated with the altered functional connectivity patterns in the slow-5 and slow-4 bands. These results indicate that frequency-dependent functional connectivity changes might provide potential biomarkers for AD pathophysiology.

  14. Functional diversity of fish in estuaries at a global extent

    OpenAIRE

    Rita P Vasconcelos; Sébastien Villéger; François Guilhaumon

    2015-01-01

    Biodiversity is currently viewed as a framework encompassing multiple facets of the variety of life, including taxonomic and functional aspects. Species richness and composition of fish assemblages in estuaries is defined by global to local processes acting on community colonization. The present study further investigates how biodiversity of fish assemblages varies among estuaries globally, by simultaneously analysing taxonomic and functional richness and diversity of assemblages. A comprehen...

  15. Altered Long- and Short-Range Functional Connectivity in Patients with Betel Quid Dependence: A Resting-State Functional MRI Study

    Directory of Open Access Journals (Sweden)

    Tao Liu

    2016-12-01

    Full Text Available Objective: Addiction is a chronic relapsing brain disease. Brain structural abnormalities may constitute an abnormal neural network that underlies the risk of drug dependence. We hypothesized that individuals with Betel Quid Dependence (BQD have functional connectivity alterations that can be described by long- and short-range functional connectivity density(FCD maps. Methods: We tested this hypothesis using functional magnetic resonance imaging (fMRI data from subjects of the Han ethnic group in Hainan, China. Here, we examined BQD individuals (n = 33 and age-, sex-, and education-matched healthy controls (HCs (n = 32 in a rs-fMRI study to observe FCD alterations associated with the severity of BQD. Results: Compared with HCs, long-range FCD was decreased in the right anterior cingulate cortex (ACC and increased in the left cerebellum posterior lobe (CPL and bilateral inferior parietal lobule (IPL in the BQD group. Short-range FCD was reduced in the right ACC and left dorsolateral prefrontal cortex (dlPFC, and increased in the left CPL. The short-range FCD alteration in the right ACC displayed a negative correlation with the Betel Quid Dependence Scale (BQDS (r=-0.432, P=0.012, and the long-range FCD alteration of left IPL showed a positive correlation with the duration of BQD(r=0.519, P=0.002 in BQD individuals. Conclusions: fMRI revealed differences in long- and short- range FCD in BQD individuals, and these alterations might be due to BQ chewing, BQ dependency, or risk factors for developing BQD.

  16. Arithmetic geometry over global function fields

    CERN Document Server

    Longhi, Ignazio; Trihan, Fabien

    2014-01-01

    This volume collects the texts of five courses given in the Arithmetic Geometry Research Programme 2009–2010 at the CRM Barcelona. All of them deal with characteristic p global fields; the common theme around which they are centered is the arithmetic of L-functions (and other special functions), investigated in various aspects. Three courses examine some of the most important recent ideas in the positive characteristic theory discovered by Goss (a field in tumultuous development, which is seeing a number of spectacular advances): they cover respectively crystals over function fields (with a number of applications to L-functions of t-motives), gamma and zeta functions in characteristic p, and the binomial theorem. The other two are focused on topics closer to the classical theory of abelian varieties over number fields: they give respectively a thorough introduction to the arithmetic of Jacobians over function fields (including the current status of the BSD conjecture and its geometric analogues, and the con...

  17. GABA FUNCTION IS ALTERED FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM: NEUROANATOMICAL AND NEUROPHYSIOLOGICAL EVIDENCE.

    Science.gov (United States)

    Thyroid hormone deficiency during development produces changes in the structure of neurons and glial cells and alters synaptic function in the hippocampus. GABAergic interneurons comprise the bulk of local inhibitory neuronal circuitry and a subpopulation of these interneurons ...

  18. Unconscious Local Motion Alters Global Image Speed

    Science.gov (United States)

    Khuu, Sieu K.; Chung, Charles Y. L.; Lord, Stephanie; Pearson, Joel

    2014-01-01

    Accurate motion perception of self and object speed is crucial for successful interaction in the world. The context in which we make such speed judgments has a profound effect on their accuracy. Misperceptions of motion speed caused by the context can have drastic consequences in real world situations, but they also reveal much about the underlying mechanisms of motion perception. Here we show that motion signals suppressed from awareness can warp simultaneous conscious speed perception. In Experiment 1, we measured global speed discrimination thresholds using an annulus of 8 local Gabor elements. We show that physically removing local elements from the array attenuated global speed discrimination. However, removing awareness of the local elements only had a small effect on speed discrimination. That is, unconscious local motion elements contributed to global conscious speed perception. In Experiment 2 we measured the global speed of the moving Gabor patterns, when half the elements moved at different speeds. We show that global speed averaging occurred regardless of whether local elements were removed from awareness, such that the speed of invisible elements continued to be averaged together with the visible elements to determine the global speed. These data suggest that contextual motion signals outside of awareness can both boost and affect our experience of motion speed, and suggest that such pooling of motion signals occurs before the conscious extraction of the surround motion speed. PMID:25503603

  19. Altered Natural Killer Cell Function in HIV-Exposed Uninfected Infants

    Directory of Open Access Journals (Sweden)

    Christiana Smith

    2017-04-01

    Full Text Available ObjectivesHIV-exposed uninfected (HEU infants have higher rates of severe and fatal infections compared with HIV-unexposed (HUU infants, likely due to immune perturbations. We hypothesized that alterations in natural killer (NK cell activity might occur in HEU infants and predispose them to severe infections.DesignCase–control study using cryopreserved peripheral blood mononuclear cells (PBMCs at birth and 6 months from HEU infants enrolled from 2002 to 2009 and HUU infants enrolled from 2011 to 2013.MethodsNK cell phenotype and function were assessed by flow cytometry after 20-h incubation with and without K562 cells.ResultsThe proportion of NK cells among PBMCs was lower at birth in 12 HEU vs. 22 HUU (1.68 vs. 10.30%, p < 0.0001 and at 6 months in 52 HEU vs. 72 HUU (3.09 vs. 4.65%, p = 0.0005. At birth, HEU NK cells demonstrated increased killing of K562 target cells (p < 0.0001 and increased expression of CD107a (21.65 vs. 12.70%, p = 0.047, but these differences resolved by 6 months. Stimulated HEU NK cells produced less interferon (IFNγ at birth (0.77 vs. 2.64%, p = 0.008 and at 6 months (4.12 vs. 8.39%, p = 0.001, and showed reduced perforin staining at 6 months (66.95 vs. 77.30%, p = 0.0008. Analysis of cell culture supernatants indicated that lower NK cell activity in HEU was associated with reduced interleukin (IL-12, IL-15, and IL-18. Addition of recombinant human IL-12 to stimulated HEU PBMCs restored IFNγ production to that seen in stimulated HUU cultures.ConclusionNK cell proportion, phenotype, and function are altered in HEU infants. NK cell cytotoxicity and degranulation are increased in HEU at birth, but HEU NK cells have reduced IFNγ and perforin production, suggesting an adequate initial response, but decreased functional reserve. NK cell function improved with addition of exogenous IL-12, implicating impaired production of IL-12 by accessory cells. Alterations in NK cell and accessory

  20. Alteration of split renal function during Captopril treatment

    International Nuclear Information System (INIS)

    Aburano, Tamio; Takayama, Teruhiko; Nakajima, Kenichi; Tonami, Norihisa; Hisada, Kinichi; Yasuhara, Shuichirou; Miyamori, Isamu; Takeda, Ryoyu

    1987-01-01

    Two different methods to evaluate the alteration of split renal function following continued Captopril treatment were studied in a total of 21 patients with hypertension. Eight patients with renovascular hypertension (five with unilateral renal artery stenosis and three with bilateral renal artery stenoses), three patients with diabetic nephropathy, one patient with primary aldosteronism, and nine patients with essential hypertension were included. The studies were performed the day prior to receiving Captopril (baseline), and 6th or 7th day following continued Captopril treatment (37.5 mg or 75 mg/day). Split effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) after injections of I-131 hippuran and Tc-99m DTPA were measured using kidney counting corrected for depth and dose, described by Schlegel and Gates. In the patients with renovascular hypertension, split GFR in the stenotic kidney was significantly decreased 6th or 7th day following continued Captopril treatment compared to a baseline value. And split ERPF in the stenotic kidney was slightly increased although significant increase of split ERPF was not shown. In the patients with diabetic nephropathy, primary aldosteronism or essential hypertension, on the other hand, split GFR was not changed and split ERPF was slightly increased. These findings suggest that the Captopril induced alterations of split renal function may be of importance for the diagnosis of renovascular hypertension. For this purpose, split GFR determination is more useful than split ERPF determination. (author)

  1. The brain functional connectome is robustly altered by lack of sleep.

    Science.gov (United States)

    Kaufmann, Tobias; Elvsåshagen, Torbjørn; Alnæs, Dag; Zak, Nathalia; Pedersen, Per Ø; Norbom, Linn B; Quraishi, Sophia H; Tagliazucchi, Enzo; Laufs, Helmut; Bjørnerud, Atle; Malt, Ulrik F; Andreassen, Ole A; Roussos, Evangelos; Duff, Eugene P; Smith, Stephen M; Groote, Inge R; Westlye, Lars T

    2016-02-15

    Sleep is a universal phenomenon necessary for maintaining homeostasis and function across a range of organs. Lack of sleep has severe health-related consequences affecting whole-body functioning, yet no other organ is as severely affected as the brain. The neurophysiological mechanisms underlying these deficits are poorly understood. Here, we characterize the dynamic changes in brain connectivity profiles inflicted by sleep deprivation and how they deviate from regular daily variability. To this end, we obtained functional magnetic resonance imaging data from 60 young, adult male participants, scanned in the morning and evening of the same day and again the following morning. 41 participants underwent total sleep deprivation before the third scan, whereas the remainder had another night of regular sleep. Sleep deprivation strongly altered the connectivity of several resting-state networks, including dorsal attention, default mode, and hippocampal networks. Multivariate classification based on connectivity profiles predicted deprivation state with high accuracy, corroborating the robustness of the findings on an individual level. Finally, correlation analysis suggested that morning-to-evening connectivity changes were reverted by sleep (control group)-a pattern which did not occur after deprivation. We conclude that both, a day of waking and a night of sleep deprivation dynamically alter the brain functional connectome. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Alteration of synaptic activity-regulating genes underlying functional improvement by long-term exposure to an enriched environment in the adult brain.

    Science.gov (United States)

    Lee, Min-Young; Yu, Ji Hea; Kim, Ji Yeon; Seo, Jung Hwa; Park, Eun Sook; Kim, Chul Hoon; Kim, Hyongbum; Cho, Sung-Rae

    2013-01-01

    Housing animals in an enriched environment (EE) enhances behavioral function. However, the mechanism underlying this EE-mediated functional improvement and the resultant changes in gene expression have yet to be elucidated. We attempted to investigate the underlying mechanisms associated with long-term exposure to an EE by evaluating gene expression patterns. We housed 6-week-old CD-1 (ICR) mice in standard cages or an EE comprising a running wheel, novel objects, and social interaction for 2 months. Motor and cognitive performances were evaluated using the rotarod test and passive avoidance test, and gene expression profile was investigated in the cerebral hemispheres using microarray and gene set enrichment analysis (GSEA). In behavioral assessment, an EE significantly enhanced rotarod performance and short-term working memory. Microarray analysis revealed that genes associated with neuronal activity were significantly altered by an EE. GSEA showed that genes involved in synaptic transmission and postsynaptic signal transduction were globally upregulated, whereas those associated with reuptake by presynaptic neurotransmitter transporters were downregulated. In particular, both microarray and GSEA demonstrated that EE exposure increased opioid signaling, acetylcholine release cycle, and postsynaptic neurotransmitter receptors but decreased Na+ / Cl- -dependent neurotransmitter transporters, including dopamine transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner. An EE enhanced motor and cognitive function through the alteration of synaptic activity-regulating genes, improving the efficient use of neurotransmitters and synaptic plasticity by the upregulation of genes associated with postsynaptic receptor activity and downregulation of presynaptic reuptake by neurotransmitter transporters.

  3. Assessment of left ventricular global function

    International Nuclear Information System (INIS)

    Breuel, H.-P.; Baehre, M.

    1985-01-01

    Radionuclide ventriculography (RNV), i.e. noninvasive evaluation of left venticular performance following the application of radionuclides has had a major impact on many aspects of cardiology and has proven its clinical value and reliability in the last few years. This article deals mainly with the changes in global left ventricular function. The clinical applications of RNV for coronary artery diseases and valvular heart diseases are described. (Auth.)

  4. Accountability for Early Childhood Education (Assessing Global Functioning).

    Science.gov (United States)

    Cassel, Russell N.

    1995-01-01

    Discusses the pacing of learning activity, knowledge of progress in student learning, teacher role, accountability in learning, feedback on knowledge of success, the global functioning assessment concept, and the mother surrogate. (RS)

  5. Altered brain rhythms and functional network disruptions involved in patients with generalized fixation-off epilepsy

    OpenAIRE

    Solana Sánchez, Ana Beatriz; Hernández Tamames, J.A.; Molina, E.; Martínez, K.; Pineda Pardo, José Ángel; Bruña Fernandez, Ricardo; Toledano, Rafael; San Antonio-Arce, Victoria; Garcia Morales, Irene; Gil Nagel, Antonio; Alfayate, E.; Álvarez Linera, Juan; Pozo Guerrero, Francisco del

    2012-01-01

    Fixation-off sensitivity (FOS) denotes the forms of epilepsy elicited by elimination of fixation. FOS-IGE patients are rare cases [1]. In a previous work [2] we showed that two FOS-IGE patients had different altered EEG rhythms when closing eyes; only beta band was altered in patient 1 while theta, alpha and beta were altered in patient 2. In the present work, we explain the relationship between the altered brain rhythms in these patients and the disruption in functional brain net...

  6. Connectomics and neuroticism: an altered functional network organization.

    Science.gov (United States)

    Servaas, Michelle N; Geerligs, Linda; Renken, Remco J; Marsman, Jan-Bernard C; Ormel, Johan; Riese, Harriëtte; Aleman, André

    2015-01-01

    The personality trait neuroticism is a potent risk marker for psychopathology. Although the neurobiological basis remains unclear, studies have suggested that alterations in connectivity may underlie it. Therefore, the aim of the current study was to shed more light on the functional network organization in neuroticism. To this end, we applied graph theory on resting-state functional magnetic resonance imaging (fMRI) data in 120 women selected based on their neuroticism score. Binary and weighted brain-wide graphs were constructed to examine changes in the functional network structure and functional connectivity strength. Furthermore, graphs were partitioned into modules to specifically investigate connectivity within and between functional subnetworks related to emotion processing and cognitive control. Subsequently, complex network measures (ie, efficiency and modularity) were calculated on the brain-wide graphs and modules, and correlated with neuroticism scores. Compared with low neurotic individuals, high neurotic individuals exhibited a whole-brain network structure resembling more that of a random network and had overall weaker functional connections. Furthermore, in these high neurotic individuals, functional subnetworks could be delineated less clearly and the majority of these subnetworks showed lower efficiency, while the affective subnetwork showed higher efficiency. In addition, the cingulo-operculum subnetwork demonstrated more ties with other functional subnetworks in association with neuroticism. In conclusion, the 'neurotic brain' has a less than optimal functional network organization and shows signs of functional disconnectivity. Moreover, in high compared with low neurotic individuals, emotion and salience subnetworks have a more prominent role in the information exchange, while sensory(-motor) and cognitive control subnetworks have a less prominent role.

  7. Phenobarbital alters hepatic Mrp2 function by direct and indirect interactions

    NARCIS (Netherlands)

    Patel, NJ; Zamek-Gliszczynski, MJ; Zhang, PJ; Han, YH; Jansen, PLM; Meier, PJ; Stieger, B; Brouwer, KLR

    Phenobarbital (PB) treatment impairs the biliary excretion of some organic anions. One mechanism may involve direct competition for biliary excretion by PB and/or a PB metabolite. Alternatively, PB may alter the expression and/or function of hepatic organic anion transport proteins. The role of

  8. Phenobarbital alters hepatic Mrp2 function by direct and indirect interactions

    NARCIS (Netherlands)

    Patel, Nita J.; Zamek-Gliszczynski, Maciej J.; Zhang, Peijin; Han, Yong-Hae; Jansen, Peter L. M.; Meier, Peter J.; Stieger, Bruno; Brouwer, Kim L. R.

    2003-01-01

    Phenobarbital (PB) treatment impairs the biliary excretion of some organic anions. One mechanism may involve direct competition for biliary excretion by PB and/or a PB metabolite. Alternatively, PB may alter the expression and/or function of hepatic organic anion transport proteins. The role of

  9. Functional Task Test: 1. Sensorimotor changes Associated with Postflight Alterations in Astronaut Functional Task Performance

    Science.gov (United States)

    Bloomberg, J. J.; Arzeno, N. H.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Miller, C. A.; Mulavara, A. P.; Platts, S. H.; Peters, B. T.; hide

    2011-01-01

    Space flight is known to cause alterations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These changes may affect a crewmember s ability to perform critical mission tasks immediately after landing on a planetary surface. The overall goal of this project is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. This presentation will focus on the sensorimotor contributions to postflight functional performance.

  10. Extinction order and altered community structure rapidly disrupt ecosystem functioning.

    Science.gov (United States)

    Larsen, Trond H; Williams, Neal M; Kremen, Claire

    2005-05-01

    By causing extinctions and altering community structure, anthropogenic disturbances can disrupt processes that maintain ecosystem integrity. However, the relationship between community structure and ecosystem functioning in natural systems is poorly understood. Here we show that habitat loss appeared to disrupt ecosystem functioning by affecting extinction order, species richness and abundance. We studied pollination by bees in a mosaic of agricultural and natural habitats in California and dung burial by dung beetles on recently created islands in Venezuela. We found that large-bodied bee and beetle species tended to be both most extinction-prone and most functionally efficient, contributing to rapid functional loss. Simulations confirmed that extinction order led to greater disruption of function than predicted by random species loss. Total abundance declined with richness and also appeared to contribute to loss of function. We demonstrate conceptually and empirically how the non-random response of communities to disturbance can have unexpectedly large functional consequences.

  11. Structural and Functional Alterations in Neocortical Circuits after Mild Traumatic Brain Injury

    Science.gov (United States)

    Vascak, Michal

    National concern over traumatic brain injury (TBI) is growing rapidly. Recent focus is on mild TBI (mTBI), which is the most prevalent injury level in both civilian and military demographics. A preeminent sequelae of mTBI is cognitive network disruption. Advanced neuroimaging of mTBI victims supports this premise, revealing alterations in activation and structure-function of excitatory and inhibitory neuronal systems, which are essential for network processing. However, clinical neuroimaging cannot resolve the cellular and molecular substrates underlying such changes. Therefore, to understand the full scope of mTBI-induced alterations it is necessary to study cortical networks on the microscopic level, where neurons form local networks that are the fundamental computational modules supporting cognition. Recently, in a well-controlled animal model of mTBI, we demonstrated in the excitatory pyramidal neuron system, isolated diffuse axonal injury (DAI), in concert with electrophysiological abnormalities in nearby intact (non-DAI) neurons. These findings were consistent with altered axon initial segment (AIS) intrinsic activity functionally associated with structural plasticity, and/or disturbances in extrinsic systems related to parvalbumin (PV)-expressing interneurons that form GABAergic synapses along the pyramidal neuron perisomatic/AIS domains. The AIS and perisomatic GABAergic synapses are domains critical for regulating neuronal activity and E-I balance. In this dissertation, we focus on the neocortical excitatory pyramidal neuron/inhibitory PV+ interneuron local network following mTBI. Our central hypothesis is that mTBI disrupts neuronal network structure and function causing imbalance of excitatory and inhibitory systems. To address this hypothesis we exploited transgenic and cre/lox mouse models of mTBI, employing approaches that couple state-of-the-art bioimaging with electrophysiology to determine the structuralfunctional alterations of excitatory and

  12. Altered Insula Connectivity under MDMA.

    Science.gov (United States)

    Walpola, Ishan C; Nest, Timothy; Roseman, Leor; Erritzoe, David; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin L

    2017-10-01

    Recent work with noninvasive human brain imaging has started to investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin- releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap. To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, double-blind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired. Results revealed decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA. The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations-both of which are known to be associated with insular functioning.

  13. Alteration of rod and cone function in children with Usher syndrome.

    Science.gov (United States)

    Malm, Eva; Ponjavic, Vesna; Möller, Claes; Kimberling, William J; Stone, Edwin S; Andréasson, Sten

    2011-01-01

    To evaluate the retinal function, with emphasis on phenotype and rate of progression, in infants and children with different genotypes of Usher syndrome. Fourteen children (2-10 years of age) with retinitis pigmentosa and hearing impairment were examined with full-field electroretinography (ERG) during general anesthesia, ophthalmologic examination, and genetic analysis. Five children were repeatedly examined (follow-up 5-10 years) with full-field ERG under local anesthesia and in 2 children multifocal ERG and optical coherence tomography (OCT) were performed. These results were compared to full-field ERG data from 58 children without retinal eye disorder. Six children were genotyped as Usher 1B, 2A, and 3A. Full-field ERG demonstrated early alterations corresponding to a rod-cone dystrophy in all children. A remaining rod function could be verified in the majority of the children up to 4 years of age. After 4 years of age, there was a further deterioration of the rod function; the progress was severe in Usher types 1 and 2 and moderate in Usher type 3. In all children, the cone function was moderately reduced, in a few cases almost normal. The results from the 58 children without retinal disorder confirm that full-field ERG during general anesthesia is reliable. Multifocal ERG confirmed a preserved central cone function and in OCT there were discrete structural alterations. Full-field ERG during general anesthesia in children with Usher syndrome demonstrates variable phenotypes and different degrees in rate of progression during childhood.

  14. Parallel Alterations of Functional Connectivity during Execution and Imagination after Motor Imagery Learning

    Science.gov (United States)

    Zhang, Rushao; Hui, Mingqi; Long, Zhiying; Zhao, Xiaojie; Yao, Li

    2012-01-01

    Background Neural substrates underlying motor learning have been widely investigated with neuroimaging technologies. Investigations have illustrated the critical regions of motor learning and further revealed parallel alterations of functional activation during imagination and execution after learning. However, little is known about the functional connectivity associated with motor learning, especially motor imagery learning, although benefits from functional connectivity analysis attract more attention to the related explorations. We explored whether motor imagery (MI) and motor execution (ME) shared parallel alterations of functional connectivity after MI learning. Methodology/Principal Findings Graph theory analysis, which is widely used in functional connectivity exploration, was performed on the functional magnetic resonance imaging (fMRI) data of MI and ME tasks before and after 14 days of consecutive MI learning. The control group had no learning. Two measures, connectivity degree and interregional connectivity, were calculated and further assessed at a statistical level. Two interesting results were obtained: (1) The connectivity degree of the right posterior parietal lobe decreased in both MI and ME tasks after MI learning in the experimental group; (2) The parallel alterations of interregional connectivity related to the right posterior parietal lobe occurred in the supplementary motor area for both tasks. Conclusions/Significance These computational results may provide the following insights: (1) The establishment of motor schema through MI learning may induce the significant decrease of connectivity degree in the posterior parietal lobe; (2) The decreased interregional connectivity between the supplementary motor area and the right posterior parietal lobe in post-test implicates the dissociation between motor learning and task performing. These findings and explanations further revealed the neural substrates underpinning MI learning and supported that

  15. Global motion perception is associated with motor function in 2-year-old children.

    Science.gov (United States)

    Thompson, Benjamin; McKinlay, Christopher J D; Chakraborty, Arijit; Anstice, Nicola S; Jacobs, Robert J; Paudel, Nabin; Yu, Tzu-Ying; Ansell, Judith M; Wouldes, Trecia A; Harding, Jane E

    2017-09-29

    The dorsal visual processing stream that includes V1, motion sensitive area V5 and the posterior parietal lobe, supports visually guided motor function. Two recent studies have reported associations between global motion perception, a behavioural measure of processing in V5, and motor function in pre-school and school aged children. This indicates a relationship between visual and motor development and also supports the use of global motion perception to assess overall dorsal stream function in studies of human neurodevelopment. We investigated whether associations between vision and motor function were present at 2 years of age, a substantially earlier stage of development. The Bayley III test of Infant and Toddler Development and measures of vision including visual acuity (Cardiff Acuity Cards), stereopsis (Lang stereotest) and global motion perception were attempted in 404 2-year-old children (±4 weeks). Global motion perception (quantified as a motion coherence threshold) was assessed by observing optokinetic nystagmus in response to random dot kinematograms of varying coherence. Linear regression revealed that global motion perception was modestly, but statistically significantly associated with Bayley III composite motor (r 2 =0.06, Pmotor scores (r 2 =0.06, pmotor and fine motor scores, but unaided visual acuity was not statistically significantly associated with any of the motor scores. These results demonstrate that global motion perception and binocular vision are associated with motor function at an early stage of development. Global motion perception can be used as a partial measure of dorsal stream function from early childhood. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Early Right Ventricular Apical Pacing-Induced Gene Expression Alterations Are Associated with Deterioration of Left Ventricular Systolic Function

    Directory of Open Access Journals (Sweden)

    Haiyan Xu

    2017-01-01

    Full Text Available The chronic high-dose right ventricular apical (RVA pacing may have deleterious effects on left ventricular (LV systolic function. We hypothesized that the expression changes of genes regulating cardiomyocyte energy metabolism and contractility were associated with deterioration of LV function in patients who underwent chronic RVA pacing. Sixty patients with complete atrioventricular block and preserved ejection fraction (EF who underwent pacemaker implantation were randomly assigned to either RVA pacing (n=30 group or right ventricular outflow tract (RVOT pacing (n=30 group. The mRNA levels of OPA1 and SERCA2a were significantly lower in the RVA pacing group at 1 month’s follow-up (both p<0.001. Early changes in the expression of selected genes OPA1 and SERCA2a were associated with deterioration in global longitudinal strain (GLS that became apparent months later (p=0.002 and p=0.026, resp. The altered expressions of genes that regulate cardiomyocyte energy metabolism and contractility measured in the peripheral blood at one month following pacemaker implantation were associated with subsequent deterioration in LV dyssynchrony and function in patients with preserved LVEF, who underwent RVA pacing.

  17. Prioritizing Candidate Disease Metabolites Based on Global Functional Relationships between Metabolites in the Context of Metabolic Pathways

    Science.gov (United States)

    Yang, Haixiu; Xu, Yanjun; Han, Junwei; Li, Jing; Su, Fei; Zhang, Yunpeng; Zhang, Chunlong; Li, Dongguo; Li, Xia

    2014-01-01

    Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY. PMID:25153931

  18. Global change and biological soil crusts: Effects of ultraviolet augmentation under altered precipitation regimes and nitrogen additions

    Science.gov (United States)

    Belnap, J.; Phillips, S.L.; Flint, S.; Money, J.; Caldwell, M.

    2008-01-01

    Biological soil crusts (BSCs), a consortium of cyanobacteria, lichens, and mosses, are essential in most dryland ecosystems. As these organisms are relatively immobile and occur on the soil surface, they are exposed to high levels of ultraviolet (UV) radiation and atmospheric nitrogen (N) deposition, rising temperatures, and alterations in precipitation patterns. In this study, we applied treatments to three types of BSCs (early, medium, and late successional) over three time periods (spring, summer, and spring-fall). In the first year, we augmented UV and altered precipitation patterns, and in the second year, we augmented UV and N. In the first year, with average air temperatures, we saw little response to our treatments except quantum yield, which was reduced in dark BSCs during one of three sample times and in Collema BSCs two of three sample times. There was more response to UV augmentation the second year when air temperatures were above average. Declines were seen in 21% of the measured variables, including quantum yield, chlorophyll a, UV-protective pigments, nitrogenase activity, and extracellular polysaccharides. N additions had some negative effects on light and dark BSCs, including the reduction of quantum yield, ??-carotene, nitrogenase activity, scytonemin, and xanthophylls. N addition had no effects on the Collema BSCs. When N was added to samples that had received augmented UV, there were only limited effects relative to samples that received UV without N. These results indicate that the negative effect of UV and altered precipitation on BSCs will be heightened as global temperatures increase, and that as their ability to produce UV-protective pigments is compromised, physiological functioning will be impaired. N deposition will only ameliorate UV impacts in a limited number of cases. Overall, increases in UV will likely lead to lowered productivity and increased mortality in BSCs through time, which, in turn, will reduce their ability to contribute

  19. Altered interhemispheric functional connectivity in patients with anisometropic and strabismic amblyopia: a resting-state fMRI study

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Minglong; Xie, Bing; Yin, Xuntao; Wang, Jian [Third Military Medical University, Department of Radiology, Southwest Hospital, 30 Gaotanyan Street, Shapingba District, Chongqing (China); Yang, Hong; Wang, Hao [Third Military Medical University, Ophthalmology Research Center, Southwest Eye Hospital/Southwest Hospital, Chongqing (China); Yu, Longhua [Third Military Medical University, Department of Radiology, Southwest Hospital, 30 Gaotanyan Street, Shapingba District, Chongqing (China); 401st Hospital of PLA, Department of Radiology, Qingdao (China); He, Sheng [University of Minnesota Twin Cities, Department of Psychology, Minneapolis, MN (United States)

    2017-05-15

    Altered brain functional connectivity has been reported in patients with amblyopia by recent neuroimaging studies. However, relatively little is known about the alterations in interhemispheric functional connectivity in amblyopia. The present study aimed to investigate the functional connectivity patterns between homotopic regions across hemispheres in patients with anisometropic and strabismic amblyopia under resting state. Nineteen monocular anisometropic amblyopia (AA), 18 strabismic amblyopia (SA), and 20 normal-sight controls (NC) were enrolled in this study. After a comprehensive ophthalmologic examination, resting-state fMRI scanning was performed in all participants. The pattern of the interhemispheric functional connectivity was measured with the voxel-mirrored homotopic connectivity (VMHC) approach. VMHC values differences within and between three groups were compared, and correlations between VMHC values and each the clinical variable were also analyzed. Altered VMHC was observed in AA and SA patients in lingual gyrus and fusiform gyrus compared with NC subjects. The altered VMHC of lingual gyrus showed a pattern of AA > SA > NC, while the altered VMHC of fusiform gyrus showed a pattern of AA > NC > SA. Moreover, the VMHC values of lingual gyrus were positively correlated with the stereoacuity both in AA and SA patients, and the VMHC values of fusiform gyrus were positively correlated with the amount of anisometropia just in AA patients. These findings suggest that interhemispheric functional coordination between several homotopic visual-related brain regions is impaired both in AA and SA patients under resting state and revealed the similarities and differences in interhemispheric functional connectivity between the anisometropic and strabismic amblyopia. (orig.)

  20. Altered interhemispheric functional connectivity in patients with anisometropic and strabismic amblyopia: a resting-state fMRI study

    International Nuclear Information System (INIS)

    Liang, Minglong; Xie, Bing; Yin, Xuntao; Wang, Jian; Yang, Hong; Wang, Hao; Yu, Longhua; He, Sheng

    2017-01-01

    Altered brain functional connectivity has been reported in patients with amblyopia by recent neuroimaging studies. However, relatively little is known about the alterations in interhemispheric functional connectivity in amblyopia. The present study aimed to investigate the functional connectivity patterns between homotopic regions across hemispheres in patients with anisometropic and strabismic amblyopia under resting state. Nineteen monocular anisometropic amblyopia (AA), 18 strabismic amblyopia (SA), and 20 normal-sight controls (NC) were enrolled in this study. After a comprehensive ophthalmologic examination, resting-state fMRI scanning was performed in all participants. The pattern of the interhemispheric functional connectivity was measured with the voxel-mirrored homotopic connectivity (VMHC) approach. VMHC values differences within and between three groups were compared, and correlations between VMHC values and each the clinical variable were also analyzed. Altered VMHC was observed in AA and SA patients in lingual gyrus and fusiform gyrus compared with NC subjects. The altered VMHC of lingual gyrus showed a pattern of AA > SA > NC, while the altered VMHC of fusiform gyrus showed a pattern of AA > NC > SA. Moreover, the VMHC values of lingual gyrus were positively correlated with the stereoacuity both in AA and SA patients, and the VMHC values of fusiform gyrus were positively correlated with the amount of anisometropia just in AA patients. These findings suggest that interhemispheric functional coordination between several homotopic visual-related brain regions is impaired both in AA and SA patients under resting state and revealed the similarities and differences in interhemispheric functional connectivity between the anisometropic and strabismic amblyopia. (orig.)

  1. Diverse effects of invasive ecosystem engineers on marine biodiversity and ecosystem functions: A global review and meta-analysis.

    Science.gov (United States)

    Guy-Haim, Tamar; Lyons, Devin A; Kotta, Jonne; Ojaveer, Henn; Queirós, Ana M; Chatzinikolaou, Eva; Arvanitidis, Christos; Como, Serena; Magni, Paolo; Blight, Andrew J; Orav-Kotta, Helen; Somerfield, Paul J; Crowe, Tasman P; Rilov, Gil

    2018-03-01

    Invasive ecosystem engineers (IEE) are potentially one of the most influential types of biological invaders. They are expected to have extensive ecological impacts by altering the physical-chemical structure of ecosystems, thereby changing the rules of existence for a broad range of resident biota. To test the generality of this expectation, we used a global systematic review and meta-analysis to examine IEE effects on the abundance of individual species and communities, biodiversity (using several indices) and ecosystem functions, focusing on marine and estuarine environments. We found that IEE had a significant effect (positive and negative) in most studies testing impacts on individual species, but the overall (cumulative) effect size was small and negative. Many individual studies showed strong IEE effects on community abundance and diversity, but the direction of effects was variable, leading to statistically non-significant overall effects in most categories. In contrast, there was a strong overall effect on most ecosystem functions we examined. IEE negatively affected metabolic functions and primary production, but positively affected nutrient flux, sedimentation and decomposition. We use the results to develop a conceptual model by highlighting pathways whereby IEE impact communities and ecosystem functions, and identify several sources of research bias in the IEE-related invasion literature. Only a few of the studies simultaneously quantified IEE effects on community/diversity and ecosystem functions. Therefore, understanding how IEE may alter biodiversity-ecosystem function relationships should be a primary focus of future studies of invasion biology. Moreover, the clear effects of IEE on ecosystem functions detected in our study suggest that scientists and environmental managers ought to examine how the effects of IEE might be manifested in the services that marine ecosystems provide to humans. © 2017 John Wiley & Sons Ltd.

  2. Quantitation of global and regional left ventricular function by MRI

    NARCIS (Netherlands)

    van der Geest, RJ; Reiber, JHC; Reiber, JHC; VanDerWall, EE

    1998-01-01

    Magnetic resonance imaging (MRI) provides several imaging strategies for assessing left ventricular function. As a three-dimensional imaging technique, all measurements can be performed without relying on geometrical assumptions. Global and regional function parameters can be derived from

  3. Alterations in renal morphology and function after ESWL therapy: evaluation with dynamic contrast-enhanced MRI

    International Nuclear Information System (INIS)

    Krestin, G.P.; Fischbach, R.; Vorreuther, R.; Schulthess, G.K. von

    1993-01-01

    Contrast-enhanced gradient-echo MRI was used to evaluate morphological and functional alterations in the kidneys after extracorporeal shock wave lithotripsy (ESWL). Dynamic MRI with a temporal resolution of 10 s per image was performed by repeated imaging in the coronal plane after administration of gadolinium-DTPA (0.1 mmol/kg) before and after ESWL for renal calculi in 25 patients. Before ESWL 22 patients had normally functioning kidneys, characterised by a marked decrease in signal intensity in the renal medulla 30-40 s after the onset of cortical perfusion. After ESWL 8 patients had functional abnormalities: in 2 cases the medullary signal decrease was disturbed throughout the whole organ, while 6 kidneys demonstrated regional loss of concentrating ability in the medulla. Morphological alterations (oedema with blurred contours and loss of corticomedullary differentiation; parenchymal haemorrhage and haemorrhage in a cortical cyst; subcapsular, perirenal and pararenal haematoma) were detected in 9 cases. Haemorrhage was encountered more often after administration of more than 2500 shock waves; however, no such correlation was seen in the kidneys with functional disturbances following ESWL therapy. MRI proved to be a sensitive method for the assessment of morphological and functional alterations after ESWL, but longer follow-up studies are required to identify the clinical impact of these early changes. (orig.)

  4. Alterations in renal morphology and function after ESWL therapy: evaluation with dynamic contrast-enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Krestin, G.P. [Dept. of Medical Radiology, University Hospital Zurich (Switzerland); Fischbach, R. [Dept. of Radiology, Univ. of Cologne (Germany); Vorreuther, R. [Dept. of Urology, Univ. of Cologne (Germany); Schulthess, G.K. von [Dept. of Medical Radiology, University Hospital Zurich (Switzerland)

    1993-06-01

    Contrast-enhanced gradient-echo MRI was used to evaluate morphological and functional alterations in the kidneys after extracorporeal shock wave lithotripsy (ESWL). Dynamic MRI with a temporal resolution of 10 s per image was performed by repeated imaging in the coronal plane after administration of gadolinium-DTPA (0.1 mmol/kg) before and after ESWL for renal calculi in 25 patients. Before ESWL 22 patients had normally functioning kidneys, characterised by a marked decrease in signal intensity in the renal medulla 30-40 s after the onset of cortical perfusion. After ESWL 8 patients had functional abnormalities: in 2 cases the medullary signal decrease was disturbed throughout the whole organ, while 6 kidneys demonstrated regional loss of concentrating ability in the medulla. Morphological alterations (oedema with blurred contours and loss of corticomedullary differentiation; parenchymal haemorrhage and haemorrhage in a cortical cyst; subcapsular, perirenal and pararenal haematoma) were detected in 9 cases. Haemorrhage was encountered more often after administration of more than 2500 shock waves; however, no such correlation was seen in the kidneys with functional disturbances following ESWL therapy. MRI proved to be a sensitive method for the assessment of morphological and functional alterations after ESWL, but longer follow-up studies are required to identify the clinical impact of these early changes. (orig.)

  5. Altered Functional Connectivity of the Basal Nucleus of Meynert in Mild Cognitive Impairment: A Resting-State fMRI Study

    Directory of Open Access Journals (Sweden)

    Hui Li

    2017-05-01

    Full Text Available Background: Cholinergic dysfunction plays an important role in mild cognitive impairment (MCI. The basal nucleus of Meynert (BNM provides the main source of cortical cholinergic innervation. Previous studies have characterized structural changes of the cholinergic basal forebrain in individuals at risk of developing Alzheimer’s disease (AD. However, whether and how functional connectivity of the BNM (BNM-FC is altered in MCI remains unknown.Objective: The aim of this study was to identify alterations in BNM-FC in individuals with MCI as compared to healthy controls (HCs, and to examine the relationship between these alterations with neuropsychological measures in individuals with MCI.Method: One-hundred-and-one MCI patients and 103 HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI. Imaging data were processed with SPM8 and CONN software. BNM-FC was examined via correlation in low frequency fMRI signal fluctuations between the BNM and all other brain voxels. Group differences were examined with a covariance analysis with age, gender, education level, mean framewise displacement (FD and global correlation (GCOR as nuisance covariates. Pearson’s correlation was conducted to evaluate the relationship between the BNM-FC and clinical assessments.Result: Compared with HCs, individuals with MCI showed significantly decreased BNM-FC in the left insula extending into claustrum (insula/claustrum. Furthermore, greater decrease in BNM-FC with insula/claustrum was associated with more severe impairment in immediate recall during Auditory Verbal Learning Test (AVLT in MCI patients.Conclusion: MCI is associated with changes in BNM-FC to the insula/claustrum in relation to cognitive impairments. These new findings may advance research of the cholinergic bases of cognitive dysfunction during healthy aging and in individuals at risk of developing AD.

  6. Altered brain network modules induce helplessness in major depressive disorder.

    Science.gov (United States)

    Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Fang, Yiru; Shen, Dinggang

    2014-10-01

    The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Altered Interhemispheric Functional Coordination in Chronic Tinnitus Patients

    Directory of Open Access Journals (Sweden)

    Yu-Chen Chen

    2015-01-01

    Full Text Available Purpose. Recent studies suggest that tinnitus may be due in part to aberrant callosal structure and interhemispheric interaction. To explore this hypothesis we use a novel method, voxel-mirrored homotopic connectivity (VMHC, to examine the resting-state interhemispheric functional connectivity and its relationships with clinical characteristics in chronic tinnitus patients. Materials and Methods. Twenty-eight chronic tinnitus patients with normal hearing thresholds and 30 age-, sex-, education-, and hearing threshold-matched healthy controls were included in this study and underwent the resting-state fMRI scanning. We computed the VMHC to analyze the interhemispheric functional coordination between homotopic points of the brain in both groups. Results. Compared to the controls, tinnitus patients showed significantly increased VMHC in the middle temporal gyrus, middle frontal gyrus, and superior occipital gyrus. In tinnitus patients, a positive correlation was found between tinnitus duration and VMHC of the uncus. Moreover, correlations between VMHC changes and tinnitus distress were observed in the transverse temporal gyrus, superior temporal pole, precentral gyrus, and calcarine cortex. Conclusions. These results show altered interhemispheric functional connectivity linked with specific tinnitus characteristics in chronic tinnitus patients, which may be implicated in the neuropathophysiology of tinnitus.

  8. Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers.

    Science.gov (United States)

    Zhang, Ming; Wang, Yanrang; Wang, Qian; Yang, Deyi; Zhang, Jingshu; Wang, Fengshan; Gu, Qing

    2013-09-01

    To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers. From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined. The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P workers (P hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.

  9. Species-Specific Effects on Ecosystem Functioning Can Be Altered by Interspecific Interactions.

    Science.gov (United States)

    Clare, David S; Spencer, Matthew; Robinson, Leonie A; Frid, Christopher L J

    2016-01-01

    Biological assemblages are constantly undergoing change, with species being introduced, extirpated and experiencing shifts in their densities. Theory and experimentation suggest that the impacts of such change on ecosystem functioning should be predictable based on the biological traits of the species involved. However, interspecific interactions could alter how species affect functioning, with the strength and sign of interactions potentially depending on environmental context (e.g. homogenous vs. heterogeneous conditions) and the function considered. Here, we assessed how concurrent changes to the densities of two common marine benthic invertebrates, Corophium volutator and Hediste diversicolor, affected the ecological functions of organic matter consumption and benthic-pelagic nutrient flux. Complementary experiments were conducted within homogenous laboratory microcosms and naturally heterogeneous field plots. When the densities of the species were increased within microcosms, interspecific interactions enhanced effects on organic matter consumption and reduced effects on nutrient flux. Trait-based predictions of how each species would affect functioning were only consistently supported when the density of the other species was low. In field plots, increasing the density of either species had a positive effect on organic matter consumption (with no significant interspecific interactions) but no effect on nutrient flux. Our results indicate that species-specific effects on ecosystem functioning can be altered by interspecific interactions, which can be either facilitative (positive) or antagonistic (negative) depending on the function considered. The impacts of biodiversity change may therefore not be predictable based solely on the biological traits of the species involved. Possible explanations for why interactions were detected in microcosms but not in the field are discussed.

  10. Species-Specific Effects on Ecosystem Functioning Can Be Altered by Interspecific Interactions.

    Directory of Open Access Journals (Sweden)

    David S Clare

    Full Text Available Biological assemblages are constantly undergoing change, with species being introduced, extirpated and experiencing shifts in their densities. Theory and experimentation suggest that the impacts of such change on ecosystem functioning should be predictable based on the biological traits of the species involved. However, interspecific interactions could alter how species affect functioning, with the strength and sign of interactions potentially depending on environmental context (e.g. homogenous vs. heterogeneous conditions and the function considered. Here, we assessed how concurrent changes to the densities of two common marine benthic invertebrates, Corophium volutator and Hediste diversicolor, affected the ecological functions of organic matter consumption and benthic-pelagic nutrient flux. Complementary experiments were conducted within homogenous laboratory microcosms and naturally heterogeneous field plots. When the densities of the species were increased within microcosms, interspecific interactions enhanced effects on organic matter consumption and reduced effects on nutrient flux. Trait-based predictions of how each species would affect functioning were only consistently supported when the density of the other species was low. In field plots, increasing the density of either species had a positive effect on organic matter consumption (with no significant interspecific interactions but no effect on nutrient flux. Our results indicate that species-specific effects on ecosystem functioning can be altered by interspecific interactions, which can be either facilitative (positive or antagonistic (negative depending on the function considered. The impacts of biodiversity change may therefore not be predictable based solely on the biological traits of the species involved. Possible explanations for why interactions were detected in microcosms but not in the field are discussed.

  11. about imagery and function of a promised global catastrophe

    OpenAIRE

    Rainer, Bettina

    2010-01-01

    The present discourse on overpopulation is functional for the defence and stabilization of the economical and political position of power of the West. It applies accordingly to the realistic social conditions / relations, which means for today the reality of a global / globalized world economy. Over and above that the discourse on overpopulation can, however, be understood as an expression of the specifically modern endeavour to acquire control over life and death and if possible to produce i...

  12. A global interaction network maps a wiring diagram of cellular function

    Science.gov (United States)

    Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N.; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D.; Pelechano, Vicent; Styles, Erin B.; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S.; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F.; Li, Sheena C.; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; Luis, Bryan-Joseph San; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W.; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G.; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M.; Moore, Claire L.; Rosebrock, Adam P.; Caudy, Amy A.; Myers, Chad L.; Andrews, Brenda; Boone, Charles

    2017-01-01

    We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing over 23 million double mutants, identifying ~550,000 negative and ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. PMID:27708008

  13. Cigarette smoke alters the secretome of lung epithelial cells.

    Science.gov (United States)

    Mossina, Alessandra; Lukas, Christina; Merl-Pham, Juliane; Uhl, Franziska E; Mutze, Kathrin; Schamberger, Andrea; Staab-Weijnitz, Claudia; Jia, Jie; Yildirim, Ali Ö; Königshoff, Melanie; Hauck, Stefanie M; Eickelberg, Oliver; Meiners, Silke

    2017-01-01

    Cigarette smoke is the most relevant risk factor for the development of lung cancer and chronic obstructive pulmonary disease. Many of its more than 4500 chemicals are highly reactive, thereby altering protein structure and function. Here, we used subcellular fractionation coupled to label-free quantitative MS to globally assess alterations in the proteome of different compartments of lung epithelial cells upon exposure to cigarette smoke extract. Proteomic profiling of the human alveolar derived cell line A549 revealed the most pronounced changes within the cellular secretome with preferential downregulation of proteins involved in wound healing and extracellular matrix organization. In particular, secretion of secreted protein acidic and rich in cysteine, a matricellular protein that functions in tissue response to injury, was consistently diminished by cigarette smoke extract in various pulmonary epithelial cell lines and primary cells of human and mouse origin as well as in mouse ex vivo lung tissue cultures. Our study reveals a previously unrecognized acute response of lung epithelial cells to cigarette smoke that includes altered secretion of proteins involved in extracellular matrix organization and wound healing. This may contribute to sustained alterations in tissue remodeling as observed in lung cancer and chronic obstructive pulmonary disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Bilingualism alters brain functional connectivity between "control" regions and "language" regions: Evidence from bimodal bilinguals.

    Science.gov (United States)

    Li, Le; Abutalebi, Jubin; Zou, Lijuan; Yan, Xin; Liu, Lanfang; Feng, Xiaoxia; Wang, Ruiming; Guo, Taomei; Ding, Guosheng

    2015-05-01

    Previous neuroimaging studies have revealed that bilingualism induces both structural and functional neuroplasticity in the dorsal anterior cingulate cortex (dACC) and the left caudate nucleus (LCN), both of which are associated with cognitive control. Since these "control" regions should work together with other language regions during language processing, we hypothesized that bilingualism may also alter the functional interaction between the dACC/LCN and language regions. Here we tested this hypothesis by exploring the functional connectivity (FC) in bimodal bilinguals and monolinguals using functional MRI when they either performed a picture naming task with spoken language or were in resting state. We found that for bimodal bilinguals who use spoken and sign languages, the FC of the dACC with regions involved in spoken language (e.g. the left superior temporal gyrus) was stronger in performing the task, but weaker in the resting state as compared to monolinguals. For the LCN, its intrinsic FC with sign language regions including the left inferior temporo-occipital part and right inferior and superior parietal lobules was increased in the bilinguals. These results demonstrate that bilingual experience may alter the brain functional interaction between "control" regions and "language" regions. For different control regions, the FC alters in different ways. The findings also deepen our understanding of the functional roles of the dACC and LCN in language processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Functional and morphological alterations of the stomach in case of irradiation of the para-aortic area

    Energy Technology Data Exchange (ETDEWEB)

    Beyer-Enke, S.A.; Gladisch, R.; Heine, M.; Georgi, M.

    1987-12-01

    Six assays were conducted in order to determine some functional and morphological parameters of the gastric mucosa in patients who underwent Co/sup 60/ irradiations of the para-aortic area. Slight as well as marked morphological alterations were observed whereas the functional alterations were found to be marked in all cases. Basal gastric secretion and serum gastrin level showed a continous reduction, however, in case of severe gastritis the stimulated secretion was increased. A possible correlation with increased tissue histamine levels is discussed.

  16. Non-concomitant cortical structural and functional alterations in sensorimotor areas following incomplete spinal cord injury

    Directory of Open Access Journals (Sweden)

    Yu Pan

    2017-01-01

    Full Text Available Brain plasticity, including anatomical changes and functional reorganization, is the physiological basis of functional recovery after spinal cord injury (SCI. The correlation between brain anatomical changes and functional reorganization after SCI is unclear. This study aimed to explore whether alterations of cortical structure and network function are concomitant in sensorimotor areas after incomplete SCI. Eighteen patients with incomplete SCI (mean age 40.94 ± 14.10 years old; male:female, 7:11 and 18 healthy subjects (37.33 ± 11.79 years old; male:female, 7:11 were studied by resting state functional magnetic resonance imaging. Gray matter volume (GMV and functional connectivity were used to evaluate cortical structure and network function, respectively. There was no significant alteration of GMV in sensorimotor areas in patients with incomplete SCI compared with healthy subjects. Intra-hemispheric functional connectivity between left primary somatosensory cortex (BA1 and left primary motor cortex (BA4, and left BA1 and left somatosensory association cortex (BA5 was decreased, as well as inter-hemispheric functional connectivity between left BA1 and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients with SCI. Functional connectivity between both BA4 areas was also decreased. The decreased functional connectivity between the left BA1 and the right BA4 positively correlated with American Spinal Injury Association sensory score in SCI patients. The results indicate that alterations of cortical anatomical structure and network functional connectivity in sensorimotor areas were non-concomitant in patients with incomplete SCI, indicating the network functional changes in sensorimotor areas may not be dependent on anatomic structure. The strength of functional connectivity within sensorimotor areas could serve as a potential imaging biomarker for assessment and prediction of sensory function in patients with incomplete SCI

  17. Multifunctional Ebselen drug functions through the activation of DNA damage response and alterations in nuclear proteins.

    Science.gov (United States)

    Azad, Gajendra K; Balkrishna, Shah Jaimin; Sathish, Narayanan; Kumar, Sangit; Tomar, Raghuvir S

    2012-01-15

    Several studies have demonstrated that Ebselen is an anti-inflammatory and anti-oxidative agent. Contrary to this, studies have also shown a high degree of cellular toxicity associated with Ebselen usage, the underlying mechanism of which remains less understood. In this study we have attempted to identify a possible molecular mechanism behind the above by investigating the effects of Ebselen on Saccharomyces cerevisiae. Significant growth arrest was documented in yeast cells exposed to Ebselen similar to that seen in presence of DNA damaging agents (including methyl methane sulfonate [MMS] and hydroxy urea [HU]). Furthermore, mutations in specific lysine residues in the histone H3 tail (H3 K56R) resulted in increased sensitivity of yeast cells to Ebselen presumably due to alterations in post-translational modifications of histone proteins towards regulating replication and DNA damage repair. Our findings suggest that Ebselen functions through activation of DNA damage response, alterations in histone modifications, activation of checkpoint kinase pathway and derepression of ribonucleotide reductases (DNA repair genes) which to the best of our knowledge is being reported for the first time. Interestingly subsequent to Ebselen exposure there were changes in global yeast protein expression and specific histone modifications, identification of which is expected to reveal a fundamental cellular mechanism underlying the action of Ebselen. Taken together these observations will help to redesign Ebselen-based therapy in clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. [The value of double contrast arthrotomography combined with cinematography in the diagnosis of functional and structural TMJ alterations].

    Science.gov (United States)

    Engelke, W; Grossniklaus, B; Sailer, H F

    1991-01-01

    Double contrast arthrotomography combined with cinematography as a diagnostic instrument establishing functional and structural TMJ alterations is evaluated for its diagnostic value and reliability within the chain of diagnostic measures applied. In 131 patients double-contrast arthrotomography was followed by a comprehensive history of joint problems, and verification of the clinical findings as well as the arthrographic diagnosis and the post-arthrographic TMJ alterations. Our interest was focussed, among others, on the question whether arthrography alone would have any therapeutic effect or produce an alteration in TMJ function.

  19. Dynamic alterations of hepatocellular function by on-demand elasticity and roughness modulation.

    Science.gov (United States)

    Uto, K; Aoyagi, T; DeForest, C A; Ebara, M

    2018-05-01

    Temperature-responsive cell culture substrates reported here can be dynamically programmed to induce bulk softening and surface roughness changes in the presence of living cells. Alterations in hepatocellular function following temporally controlled substrate softening depend on the extent of stiff mechanical priming prior to user-induced material transition.

  20. Altered functional connectivity of amygdala underlying the neuromechanism of migraine pathogenesis.

    Science.gov (United States)

    Chen, Zhiye; Chen, Xiaoyan; Liu, Mengqi; Dong, Zhao; Ma, Lin; Yu, Shengyuan

    2017-12-01

    The amygdala is a large grey matter complex in the limbic system, and it may contribute in the neurolimbic pain network in migraine. However, the detailed neuromechanism remained to be elucidated. The objective of this study is to investigate the amygdala structural and functional changes in migraine and to elucidate the mechanism of neurolimbic pain-modulating in the migraine pathogenesis. Conventional MRI, 3D structure images and resting state functional MRI were performed in 18 normal controls (NC), 18 patients with episodic migraine (EM), and 16 patients with chronic migraine (CM). The amygdala volume was measured using FreeSurfer software and the functional connectivity (FC) of bilateral amygdala was computed over the whole brain. Analysis of covariance was performed on the individual FC maps among groups. The increased FC of left amygdala was observed in EM compared with NC, and the decreased of right amygdala was revealed in CM compared with NC. The increased FC of bilateral amygdala was observed in CM compared with EM. The correlation analysis showed a negative correlation between the score of sleep quality (0, normal; 1, mild sleep disturbance; 2, moderate sleep disturbance; 3, serious sleep disturbance) and the increased FC strength of left amygdala in EM compared with NC, and a positive correlation between the score of sleep quality and the increased FC strength of left amygdala in CM compared with EM, and other clinical variables showed no significant correlation with altered FC of amygdala. The altered functional connectivity of amygdala demonstrated that neurolimbic pain network contribute in the EM pathogenesis and CM chronicization.

  1. Altered functional brain connectivity in patients with visually induced dizziness

    Directory of Open Access Journals (Sweden)

    Angelique Van Ombergen

    2017-01-01

    Conclusions: We found alterations in the visual and vestibular cortical network in VID patients that could underlie the typical VID symptoms such as a worsening of their vestibular symptoms when being exposed to challenging visual stimuli. These preliminary findings provide the first insights into the underlying functional brain connectivity in VID patients. Future studies should extend these findings by employing larger sample sizes, by investigating specific task-based paradigms in these patients and by exploring the implications for treatment.

  2. Perfusion deficits and functional connectivity alterations in patients with post-traumatic stress disorder

    Science.gov (United States)

    Liu, Yang; Li, Baojuan; Zhang, Xi; Zhang, Linchuan; Li, Liang; Lu, Hongbing

    2016-03-01

    To explore the alteration in cerebral blood flow (CBF) and functional connectivity between survivors with recent onset post-traumatic stress disorder (PTSD) and without PTSD, survived from the same coal mine flood disaster. In this study, a processing pipeline using arterial spin labeling (ASL) sequence was proposed. Considering low spatial resolution of ASL sequence, a linear regression method was firstly used to correct the partial volume (PV) effect for better CBF estimation. Then the alterations of CBF between two groups were analyzed using both uncorrected and PV-corrected CBF maps. Based on altered CBF regions detected from the CBF analysis as seed regions, the functional connectivity abnormities in PTSD patients was investigated. The CBF analysis using PV-corrected maps indicates CBF deficits in the bilateral frontal lobe, right superior frontal gyrus and right corpus callosum of PTSD patients, while only right corpus callosum was identified in uncorrected CBF analysis. Furthermore, the regional CBF of the right superior frontal gyrus exhibits significantly negative correlation with the symptom severity in PTSD patients. The resting-state functional connectivity indicates increased connectivity between left frontal lobe and right parietal lobe. These results indicate that PV-corrected CBF exhibits more subtle perfusion changes and may benefit further perfusion and connectivity analysis. The symptom-specific perfusion deficits and aberrant connectivity in above memory-related regions may be putative biomarkers for recent onset PTSD induced by a single prolonged trauma exposure and help predict the severity of PTSD.

  3. Electroencephalographic power and coherence analyses suggest altered brain function in abstinent male heroin-dependent patients

    NARCIS (Netherlands)

    Franken, Ingmar H. A.; Stam, Cornelis J.; Hendriks, Vincent M.; van den Brink, Wim

    2004-01-01

    Previous studies have shown that drug abuse is associated with altered brain function. However, studies of heroin abuse-related brain dysfunctions are scarce. Electroencephalographic ( EEG) power and coherence analyses are two important tools for examining the effects of drugs on brain function. In

  4. Global existence for Volterra-Fredholm type neutral impulsive functional integrodifferential equations

    Directory of Open Access Journals (Sweden)

    V. Vijayakumar

    2012-09-01

    Full Text Available n this paper, we study the global existence of solutions for the initial value problems for Volterra-Fredholm type neutral impulsive functional integrodifferential equations. Using the Leray-Schauder's Alternative theorem, we derive conditions under which a solution exists globally. An application is provided to illustrate the theory.

  5. A method for improving global pyranometer measurements by modeling responsivity functions

    Energy Technology Data Exchange (ETDEWEB)

    Lester, A. [Smith College, Northampton, MA 01063 (United States); Myers, D.R. [National Renewable Energy Laboratory, 1617 Cole Blvd., Golden, CO 80401 (United States)

    2006-03-15

    Accurate global solar radiation measurements are crucial to climate change research and the development of solar energy technologies. Pyranometers produce an electrical signal proportional to global irradiance. The signal-to-irradiance ratio is the responsivity (RS) of the instrument (RS=signal/irradiance=microvolts/(W/m{sup 2})). Most engineering measurements are made using a constant RS. It is known that RS varies with day of year, zenith angle, and net infrared radiation. This study proposes a method to find an RS function to model a pyranometer's changing RS. Using a reference irradiance calculated from direct and diffuse instruments, we found instantaneous RS for two global pyranometers over 31 sunny days in a two-year period. We performed successive independent regressions of the error between the constant and instantaneous RS with respect to zenith angle, day of year, and net infrared to obtain an RS function. An alternative method replaced the infrared regression with an independently developed technique to account for thermal offset. Results show improved uncertainties with the function method than with the single-calibration value. Lower uncertainties also occur using a black-and-white (8-48), rather than all-black (PSP), shaded pyranometer as the diffuse reference instrument. We conclude that the function method is extremely effective in reducing uncertainty in the irradiance measurements for global PSP pyranometers if they are calibrated at the deployment site. Furthermore, it was found that the function method accounts for the pyranometer's thermal offset, rendering further corrections unnecessary. The improvements in irradiance data achieved in this study will serve to increase the accuracy of solar energy assessments and atmospheric research. (author)

  6. State-related functional integration and functional segregation brain networks in schizophrenia.

    Science.gov (United States)

    Yu, Qingbao; Sui, Jing; Kiehl, Kent A; Pearlson, Godfrey; Calhoun, Vince D

    2013-11-01

    Altered topological properties of brain connectivity networks have emerged as important features of schizophrenia. The aim of this study was to investigate how the state-related modulations to graph measures of functional integration and functional segregation brain networks are disrupted in schizophrenia. Firstly, resting state and auditory oddball discrimination (AOD) fMRI data of healthy controls (HCs) and schizophrenia patients (SZs) were decomposed into spatially independent components (ICs) by group independent component analysis (ICA). Then, weighted positive and negative functional integration (inter-component networks) and functional segregation (intra-component networks) brain networks were built in each subject. Subsequently, connectivity strength, clustering coefficient, and global efficiency of all brain networks were statistically compared between groups (HCs and SZs) in each state and between states (rest and AOD) within group. We found that graph measures of negative functional integration brain network and several positive functional segregation brain networks were altered in schizophrenia during AOD task. The metrics of positive functional integration brain network and one positive functional segregation brain network were higher during the resting state than during the AOD task only in HCs. These findings imply that state-related characteristics of both functional integration and functional segregation brain networks are impaired in schizophrenia which provides new insight into the altered brain performance in this brain disorder. © 2013.

  7. Altered Brain Functional Connectivity in Betel Quid-Dependent Chewers.

    Science.gov (United States)

    Huang, Xiaojun; Pu, Weidan; Liu, Haihong; Li, Xinmin; Greenshaw, Andrew J; Dursun, Serdar M; Xue, Zhimin; Liu, Zhening

    2017-01-01

    Betel quid (BQ) is a common psychoactive substance worldwide with particularly high usage in many Asian countries. This study aimed to explore the effect of BQ use on functional connectivity by comparing global functional brain networks and their subset between BQ chewers and healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) was obtained from 24 betel quid-dependent (BQD) male chewers and 27 healthy male individuals on a 3.0T scanner. We used independent component analysis (ICA) to determine components that represent the brain's functional networks and their spatial aspects of functional connectivity. Two sample t -tests were used to identify the functional connectivity differences in each network between these two groups. Seventeen networks were identified by ICA. Nine of them showed connectivity differences between BQD and HCs (two sample t -tests, p  betel quid dependence scale scores were positively related to the increased functional connectivity in the orbitofrontal ( r  = 0.39, p  = 0.03) while negatively related to the decreased functional connectivity in medial frontal/anterior cingulate networks ( r  = -0.35, p  = 0.02). Our findings provide further evidence that BQ chewing may lead to brain functional connectivity changes, which may play a key role in the psychological and physiological effects of BQ.

  8. Multiple lupus-associated ITGAM variants alter Mac-1 functions on neutrophils.

    Science.gov (United States)

    Zhou, Yebin; Wu, Jianming; Kucik, Dennis F; White, Nathan B; Redden, David T; Szalai, Alexander J; Bullard, Daniel C; Edberg, Jeffrey C

    2013-11-01

    Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the nonsynonymous SNPs rs1143679, rs1143678, and rs1143683) are associated with systemic lupus erythematosus (SLE). ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biologic functions of neutrophil Mac-1. Neutrophils from ITGAM-genotyped and -sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement-coated erythrocytes, serum-treated zymosan, heat-treated zymosan, and IgG-coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α-stimulated endothelial cells, was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry. Mac-1-mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation. The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE

  9. A whole-brain computational modeling approach to explain the alterations in resting-state functional connectivity during progression of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Murat Demirtaş

    2017-01-01

    Full Text Available Alzheimer's disease (AD is the most common dementia with dramatic consequences. The research in structural and functional neuroimaging showed altered brain connectivity in AD. In this study, we investigated the whole-brain resting state functional connectivity (FC of the subjects with preclinical Alzheimer's disease (PAD, mild cognitive impairment due to AD (MCI and mild dementia due to Alzheimer's disease (AD, the impact of APOE4 carriership, as well as in relation to variations in core AD CSF biomarkers. The synchronization in the whole-brain was monotonously decreasing during the course of the disease progression. Furthermore, in AD patients we found widespread significant decreases in functional connectivity (FC strengths particularly in the brain regions with high global connectivity. We employed a whole-brain computational modeling approach to study the mechanisms underlying these alterations. To characterize the causal interactions between brain regions, we estimated the effective connectivity (EC in the model. We found that the significant EC differences in AD were primarily located in left temporal lobe. Then, we systematically manipulated the underlying dynamics of the model to investigate simulated changes in FC based on the healthy control subjects. Furthermore, we found distinct patterns involving CSF biomarkers of amyloid-beta (Aβ1−42 total tau (t-tau and phosphorylated tau (p-tau. CSF Aβ1−42 was associated to the contrast between healthy control subjects and clinical groups. Nevertheless, tau CSF biomarkers were associated to the variability in whole-brain synchronization and sensory integration regions. These associations were robust across clinical groups, unlike the associations that were found for CSF Aβ1−42. APOE4 carriership showed no significant correlations with the connectivity measures.

  10. Altered thalamic functional connectivity in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yaou; Liang, Peipeng; Duan, Yunyun; Huang, Jing; Ren, Zhuoqiong; Jia, Xiuqin [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Dong, Huiqing; Ye, Jing [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shi, Fu-Dong [Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Butzkueven, Helmut [Department of Medicine, University of Melbourne, Parkville 3010 (Australia); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2015-04-15

    Highlights: •We demonstrated decreased connectivity between thalamus and cortical regions in MS. •Increased intra- and inter-thalamic connectivity was also observed in MS. •The increased functional connectivity is attenuated by increasing disease duration. -- Abstract: Objective: To compare thalamic functional connectivity (FC) in patients with multiple sclerosis (MS) and healthy controls (HC), and correlate these connectivity measures with other MRI and clinical variables. Methods: We employed resting-state functional MRI (fMRI) to examine changes in thalamic connectivity by comparing thirty-five patients with MS and 35 age- and sex-matched HC. Thalamic FC was investigated by correlating low frequency fMRI signal fluctuations in thalamic voxels with voxels in all other brain regions. Additionally thalamic volume fraction (TF), T2 lesion volume (T2LV), EDSS and disease duration were recorded and correlated with the FC changes. Results: MS patients were found to have a significantly lower TF than HC in bilateral thalami. Compared to HC, the MS group showed significantly decreased FC between thalamus and several brain regions including right middle frontal and parahippocampal gyri, and the left inferior parietal lobule. Increased intra- and inter-thalamic FC was observed in the MS group compared to HC. These FC alterations were not correlated with T2LV, thalamic volume or lesions. In the MS group, however, there was a negative correlation between disease duration and inter-thalamic connectivity (r = −0.59, p < 0.001). Conclusion: We demonstrated decreased FC between thalamus and several cortical regions, while increased intra- and inter-thalamic connectivity in MS patients. These complex functional changes reflect impairments and/or adaptations that are independent of T2LV, thalamic volume or presence of thalamic lesions. The negative correlation between disease duration and inter-thalamic connectivity could indicate an adaptive role of thalamus that is

  11. Altered structural and functional thalamocortical networks in secondarily generalized extratemporal lobe seizures

    Directory of Open Access Journals (Sweden)

    Syu-Jyun Peng

    2017-01-01

    Full Text Available Structural and functional abnormalities in the thalamocortical network in primary generalized epilepsies or mesial temporal lobe epilepsy have recently been identified by voxel-wise analyses of neuroimaging. However, evidence is needed regarding the profiles of the thalamocortical network in patients with secondarily generalized seizures from focal neocortical sources. We used high-resolution T1-weighted, diffusion-tensor and resting-state functional MR imaging (rs-fMRI to examine 16 patients with secondarily generalized extratemporal lobe seizures and 16 healthy controls. All the patients were medically effective and MRI-negative. Using whole brain voxel-based morphometry (VBM to compare the patients with the normal controls, we observed significantly decreased gray matter (GM density in the thalamus and 3 frontal gyri and significantly reduced white matter (WM fractional anisotropy (FA in the bilateral anterior corona radiata of the patients. Alterations in the thalamocortical functional connectivity with different cortices were identified by the rs-fMRI analysis seeding of the whole thalamus. The prefrontal gyri with the greatest functional connectivity were also traced by seeding a sub-thalamic region that is demarcated in an atlas, in which the thalamic parcellation is based on the WM connectivity to the cortices. This sub-thalamic region anatomically contains the mediodorsal thalamic nucleus where, concordantly, there was a significant decrease in thalamic GM density in the VBM study. In contrast to the negative correlation between the disease duration and reduced thalamic densities and subcortical FA values, the strength of the functional thalamocortical connectivity had a paradoxical correlation. Our results conclusively indicate that generalized seizures with a focal cortical source are associated with structural and functional alterations in the thalamocortical network.

  12. No Global War? A Role for Democratic Global Federalism

    Directory of Open Access Journals (Sweden)

    Myron J. Frankman

    2015-08-01

    Full Text Available In fact, the issue is not whether we shall be governed globally, but rather by whom and on what basis. The international realm is not one of anarchy as the realists would have us believe, but rather one of order: of rules, procedures and accepted norms of behavior associated in part with what are termed "international regimes" (Krasner 1983, each dedicated in principle to a separate functional domain. Global governance is not something that is to be created, but rather something to be altered in the public interest. The governance of the globe is currently configured by a shifting set of ill-coordinated actors: among them the one remaining super-power and, to a lesser extent, other strong states, as well as powerful individuals and a number of large transnational corporations and financial institutions. Whereas Le Monde Diplomatique (1995 speaks oflcs nouveaux maitres du monde, Robert Cox has summed up our current system of global governance with the phrase nebuleuse: "There is, in effect, no explicit political or authority structure for the global economy. There is, nevertheless, something there that remains to be deciphered, something that could be described by the French word nebulcuse or by the notion of 'governance without government."'

  13. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications.

    Science.gov (United States)

    Levkau, Bodo

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction.

  14. Shifts in the phylogenetic structure and functional capacity of soil microbial communities follow alteration of native tussock grassland ecosystems

    NARCIS (Netherlands)

    Wakelin, Steven A.; Barratt, Barbara I.P.; Gerard, Emily; Gregg, Adrienne L.; Brodie, Eoin L.; Andersen, Gary L.; DeSantis, Todd Z.; Zhou, Jizhong; He, Zhili; Kowalchuk, George A.; O'Callaghan, Maureen

    Globally, tussock-based grasslands are being modified to increase productive capacity. The impacts of cultivation and over-sowing with exotic grass and legumes on soil microbiology were assessed at four sites in New Zealand which differed in soil type, climate and vegetation. Primary alteration of

  15. Global environmental change effects on plant community composition trajectories depend upon management legacies

    NARCIS (Netherlands)

    Perring, Michael P.; Bernhardt-Römermann, Markus; Baeten, Lander; Midolo, Gabriele; Blondeel, Haben; Depauw, Leen; Landuyt, Dries; Maes, Sybryn L.; Lombaerde, De Emiel; Carón, Maria Mercedes; Vellend, Mark; Brunet, Jörg; Chudomelová, Markéta; Decocq, Guillaume; Diekmann, Martin; Dirnböck, Thomas; Dörfler, Inken; Durak, Tomasz; Frenne, De Pieter; Gilliam, Frank S.; Hédl, Radim; Heinken, Thilo; Hommel, Patrick; Jaroszewicz, Bogdan; Kirby, Keith J.; Kopecký, Martin; Lenoir, Jonathan; Li, Daijiang; Máliš, František; Mitchell, Fraser J.G.; Naaf, Tobias; Newman, Miles; Petřík, Petr; Reczyńska, Kamila; Schmidt, Wolfgang; Standovár, Tibor; Świerkosz, Krzysztof; Calster, Van Hans; Vild, Ondřej; Wagner, Eva Rosa; Wulf, Monika; Verheyen, Kris

    2018-01-01

    The contemporary state of functional traits and species richness in plant communities depends on legacy effects of past disturbances. Whether temporal responses of community properties to current environmental changes are altered by such legacies is, however, unknown. We expect global environmental

  16. Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study.

    Directory of Open Access Journals (Sweden)

    Sophia Mueller

    Full Text Available Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA. We applied diffusion tensor imaging (DTI, voxel-based morphometry (VBM and resting state functional connectivity magnetic resonance imaging (fcMRI to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male and 12 healthy controls (mean age 33.3, SD 9.0, 8 male. Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration.

  17. Infections are a global issue: infection addresses global issues.

    Science.gov (United States)

    Grobusch, M P; Calleri, G; Bogner, J R

    2012-12-01

    Infections are of unifying global concern, despite regional differences in disease epidemiology, clinical appearance and the instruments to tackle them. The primary aim of Infection is "to be a forum for the presentation and discussion of clinically relevant information on infectious diseases… from all over the world". To that end, and as a reflection of the global burden of infectious diseases, we intend to increase the number of high-quality contributions from authors addressing the aetiology, pathogenesis, diagnosis and treatment of infectious diseases from outside Europe and the affluent North (Chang et al. Infection 40:359-365, 2012; Misra et al. Infection 40:125-130, 2012). The Editorial Board of Infection envisages the journal as an interface between where infectious diseases meet and mix between "North and South"--i.e., the field of travel medicine--frequently functioning as a sentinel for altered/novel disease activities that are encountered as imported conditions. With the change in generation on the Editorial Board, Infection aims to expand the areas of tropical medicine, travel medicine and global health with its own section editors (GC and MPG). Contributions from outside Europe are actively encouraged.

  18. Moderate perinatal thyroid hormone insufficiency alters visual system function in adult rats.

    Science.gov (United States)

    Boyes, William K; Degn, Laura; George, Barbara Jane; Gilbert, Mary E

    2018-04-21

    Thyroid hormone (TH) is critical for many aspects of neurodevelopment and can be disrupted by a variety of environmental contaminants. Sensory systems, including audition and vision are vulnerable to TH insufficiencies, but little data are available on visual system development at less than severe levels of TH deprivation. The goal of the current experiments was to explore dose-response relations between graded levels of TH insufficiency during development and the visual function of adult offspring. Pregnant Long Evans rats received 0 or 3 ppm (Experiment 1), or 0, 1, 2, or 3 ppm (Experiment 2) of propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis, in drinking water from gestation day (GD) 6 to postnatal day (PN) 21. Treatment with PTU caused dose-related reductions of serum T4, with recovery on termination of exposure, and euthyroidism by the time of visual function testing. Tests of retinal (electroretinograms; ERGs) and visual cortex (visual evoked potentials; VEPs) function were assessed in adult offspring. Dark-adapted ERG a-waves, reflecting rod photoreceptors, were increased in amplitude by PTU. Light-adapted green flicker ERGs, reflecting M-cone photoreceptors, were reduced by PTU exposure. UV-flicker ERGs, reflecting S-cones, were not altered. Pattern-elicited VEPs were significantly reduced by 2 and 3 ppm PTU across a range of stimulus contrast values. The slope of VEP amplitude-log contrast functions was reduced by PTU, suggesting impaired visual contrast gain. Visual contrast gain primarily reflects function of visual cortex, and is responsible for adjusting sensitivity of perceptual mechanisms in response to changing visual scenes. The results indicate that moderate levels of pre-and post-natal TH insufficiency led to alterations in visual function of adult rats, including both retinal and visual cortex sites of dysfunction. Copyright © 2018. Published by Elsevier B.V.

  19. Altered Neural Activity Associated with Mindfulness during Nociception: A Systematic Review of Functional MRI

    Directory of Open Access Journals (Sweden)

    Elena Bilevicius

    2016-04-01

    Full Text Available Objective: To assess the neural activity associated with mindfulness-based alterations of pain perception. Methods: The Cochrane Central, EMBASE, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched on 2 February 2016. Titles, abstracts, and full-text articles were independently screened by two reviewers. Data were independently extracted from records that included topics of functional neuroimaging, pain, and mindfulness interventions. Results: The literature search produced 946 total records, of which five met the inclusion criteria. Records reported pain in terms of anticipation (n = 2, unpleasantness (n = 5, and intensity (n = 5, and how mindfulness conditions altered the neural activity during noxious stimulation accordingly. Conclusions: Although the studies were inconsistent in relating pain components to neural activity, in general, mindfulness was able to reduce pain anticipation and unpleasantness ratings, as well as alter the corresponding neural activity. The major neural underpinnings of mindfulness-based pain reduction consisted of altered activity in the anterior cingulate cortex, insula, and dorsolateral prefrontal cortex.

  20. Altered Neural Activity Associated with Mindfulness during Nociception: A Systematic Review of Functional MRI.

    Science.gov (United States)

    Bilevicius, Elena; Kolesar, Tiffany A; Kornelsen, Jennifer

    2016-04-19

    To assess the neural activity associated with mindfulness-based alterations of pain perception. The Cochrane Central, EMBASE, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched on 2 February 2016. Titles, abstracts, and full-text articles were independently screened by two reviewers. Data were independently extracted from records that included topics of functional neuroimaging, pain, and mindfulness interventions. The literature search produced 946 total records, of which five met the inclusion criteria. Records reported pain in terms of anticipation (n = 2), unpleasantness (n = 5), and intensity (n = 5), and how mindfulness conditions altered the neural activity during noxious stimulation accordingly. Although the studies were inconsistent in relating pain components to neural activity, in general, mindfulness was able to reduce pain anticipation and unpleasantness ratings, as well as alter the corresponding neural activity. The major neural underpinnings of mindfulness-based pain reduction consisted of altered activity in the anterior cingulate cortex, insula, and dorsolateral prefrontal cortex.

  1. Altered Network Oscillations and Functional Connectivity Dynamics in Children Born Very Preterm.

    Science.gov (United States)

    Moiseev, Alexander; Doesburg, Sam M; Herdman, Anthony T; Ribary, Urs; Grunau, Ruth E

    2015-09-01

    Structural brain connections develop atypically in very preterm children, and altered functional connectivity is also evident in fMRI studies. Such alterations in brain network connectivity are associated with cognitive difficulties in this population. Little is known, however, about electrophysiological interactions among specific brain networks in children born very preterm. In the present study, we recorded magnetoencephalography while very preterm children and full-term controls performed a visual short-term memory task. Regions expressing task-dependent activity changes were identified using beamformer analysis, and inter-regional phase synchrony was calculated. Very preterm children expressed altered regional recruitment in distributed networks of brain areas, across standard physiological frequency ranges including the theta, alpha, beta and gamma bands. Reduced oscillatory synchrony was observed among task-activated brain regions in very preterm children, particularly for connections involving areas critical for executive abilities, including middle frontal gyrus. These findings suggest that inability to recruit neurophysiological activity and interactions in distributed networks including frontal regions may contribute to difficulties in cognitive development in children born very preterm.

  2. Prevention of Synaptic Alterations and Neurotoxic Effects of PAMAM Dendrimers by Surface Functionalization

    Directory of Open Access Journals (Sweden)

    Felipe Vidal

    2017-12-01

    Full Text Available One of the most studied nanocarriers for drug delivery are polyamidoamine (PAMAM dendrimers. However, the alterations produced by PAMAM dendrimers in neuronal function have not been thoroughly investigated, and important aspects such as effects on synaptic transmission remain unexplored. We focused on the neuronal activity disruption induced by dendrimers and the possibility to prevent these effects by surface chemical modifications. Therefore, we studied the effects of fourth generation PAMAM with unmodified positively charged surface (G4 in hippocampal neurons, and compared the results with dendrimers functionalized in 25% of their surface groups with folate (PFO25 and polyethylene glycol (PPEG25. G4 dendrimers significantly reduced cell viability at 1 µM, which was attenuated by both chemical modifications, PPEG25 being the less cytotoxic. Patch clamp recordings demonstrated that G4 induced a 7.5-fold increment in capacitive currents as a measure of membrane permeability. Moreover, treatment with this dendrimer increased intracellular Ca2+ by 8-fold with a complete disruption of transients pattern, having as consequence that G4 treatment increased the synaptic vesicle release and frequency of synaptic events by 2.4- and 3-fold, respectively. PFO25 and PPEG25 treatments did not alter membrane permeability, total Ca2+ intake, synaptic vesicle release or synaptic activity frequency. These results demonstrate that cationic G4 dendrimers have neurotoxic effects and induce alterations in normal synaptic activity, which are generated by the augmentation of membrane permeability and a subsequent intracellular Ca2+ increase. Interestingly, these toxic effects and synaptic alterations are prevented by the modification of 25% of PAMAM surface with either folate or polyethylene glycol.

  3. A global genetic interaction network maps a wiring diagram of cellular function.

    Science.gov (United States)

    Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D; Pelechano, Vicent; Styles, Erin B; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F; Li, Sheena C; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; San Luis, Bryan-Joseph; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M; Moore, Claire L; Rosebrock, Adam P; Caudy, Amy A; Myers, Chad L; Andrews, Brenda; Boone, Charles

    2016-09-23

    We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. Copyright © 2016, American Association for the Advancement of Science.

  4. Anti-tachycardia therapy can improve altered cardiac adrenergic function in tachycardia-induced cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ohkusu, Yasuo; Takahashi, Nobukazu; Ishikawa, Toshiyuki [Yokohama City Univ. (Japan). School of Medicine] [and others

    2002-11-01

    We investigated whether anti-tachycardia therapy might improve the altered cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients with heart failure, consisting of 8 patients with TC (43.6{+-}10.0 yrs) and 15 with DCM (45.3{+-}8.2 yrs). TC was determined as impairment of left ventricular function secondary to chronic or very frequent arrhythmia during more than 10% of the day. All patients were receiving anti-tachycardia treatment. Cardiac {sup 123}I-MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and after treatment. Left ventricular ejection fraction (LVEF) was also assessed. In the baseline study, H/M and LVEF showed no difference between TC and DCM (2.21{+-}0.44 vs. 2.10{+-}0.42, 35.3{+-}13.1 vs. 36.0{+-}10.9%, respectively). After treatment, the degree of change in H/M and LVEF differed significantly (0.41{+-}0.34 vs. 0.08{+-}0.20, 20.5{+-}14.4 vs. -2.1{+-}9.6%, p<0.01). In TC, heart failure improved after a shorter duration of treatment (p<0.05). In conclusion, anti-tachycardia therapy can improve altered cardiac adrenergic function and systolic function in patients with TC over a shorter period than in those with DCM. (author)

  5. Adolescent social defeat alters markers of adult dopaminergic function.

    Science.gov (United States)

    Novick, Andrew M; Forster, Gina L; Tejani-Butt, Shanaz M; Watt, Michael J

    2011-08-10

    Stressful experiences during adolescence can alter the trajectory of neural development and contribute to psychiatric disorders in adulthood. We previously demonstrated that adolescent male rats exposed to repeated social defeat stress show changes in mesocorticolimbic dopamine content both at baseline and in response to amphetamine when tested in adulthood. In the present study we examined whether markers of adult dopamine function are also compromised by adolescent experience of social defeat. Given that the dopamine transporter as well as dopamine D1 receptors act as regulators of psychostimulant action, are stress sensitive and undergo changes during adolescence, quantitative autoradiography was used to measure [(3)H]-GBR12935 binding to the dopamine transporter and [(3)H]-SCH23390 binding to dopamine D1 receptors, respectively. Our results indicate that social defeat during adolescence led to higher dopamine transporter binding in the infralimbic region of the medial prefrontal cortex and higher dopamine D1 receptor binding in the caudate putamen, while other brain regions analyzed were comparable to controls. Thus it appears that social defeat during adolescence causes specific changes to the adult dopamine system, which may contribute to behavioral alterations and increased drug seeking. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Physiological and Functional Alterations after Spaceflight and Bed Rest.

    Science.gov (United States)

    Mulavara, Ajitkumar P; Peters, Brian T; Miller, Chris A; Kofman, Igor S; Reschke, Millard F; Taylor, Laura C; Lawrence, Emily L; Wood, Scott J; Laurie, Steven S; Lee, Stuart M C; Buxton, Roxanne E; May-Phillips, Tiffany R; Stenger, Michael B; Ploutz-Snyder, Lori L; Ryder, Jeffrey W; Feiveson, Alan H; Bloomberg, Jacob J

    2018-04-03

    Exposure to microgravity causes alterations in multiple physiological systems, potentially impacting the ability of astronauts to perform critical mission tasks. The goal of this study was to determine the effects of spaceflight on functional task performance and to identify the key physiological factors contributing to their deficits. A test battery comprised of 7 functional tests and 15 physiological measures was used to investigate the sensorimotor, cardiovascular and neuromuscular adaptations to spaceflight. Astronauts were tested before and after 6-month spaceflights. Subjects were also tested before and after 70 days of 6° head-down bed rest, a spaceflight analog, to examine the role of axial body unloading on the spaceflight results. These subjects included Control and Exercise groups to examine the effects of exercise during bed rest. Spaceflight subjects showed the greatest decrement in performance during functional tasks that required the greatest demand for dynamic control of postural equilibrium which was paralleled by similar decrements in sensorimotor tests that assessed postural and dynamic gait control. Other changes included reduced lower limb muscle performance and increased heart rate to maintain blood pressure. Exercise performed during bed rest prevented detrimental change in neuromuscular and cardiovascular function, however, both bed rest groups experienced functional and balance deficits similar to spaceflight subjects. Bed rest data indicates that body support unloading experienced during spaceflight contributes to postflight postural control dysfunction. Further, the bed rest results in the Exercise group of subjects confirm that resistance and aerobic exercises performed during spaceflight can play an integral role in maintaining neuromuscular and cardiovascular function, which can help in reducing decrements in functional performance. These results indicate that a countermeasure to mitigate postflight postural control dysfunction is

  7. A branch and bound algorithm for the global optimization of Hessian Lipschitz continuous functions

    KAUST Repository

    Fowkes, Jaroslav M.

    2012-06-21

    We present a branch and bound algorithm for the global optimization of a twice differentiable nonconvex objective function with a Lipschitz continuous Hessian over a compact, convex set. The algorithm is based on applying cubic regularisation techniques to the objective function within an overlapping branch and bound algorithm for convex constrained global optimization. Unlike other branch and bound algorithms, lower bounds are obtained via nonconvex underestimators of the function. For a numerical example, we apply the proposed branch and bound algorithm to radial basis function approximations. © 2012 Springer Science+Business Media, LLC.

  8. Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function.

    Directory of Open Access Journals (Sweden)

    Kwok Yeung Tsang

    2007-03-01

    Full Text Available In protein folding and secretion disorders, activation of endoplasmic reticulum (ER stress signaling (ERSS protects cells, alleviating stress that would otherwise trigger apoptosis. Whether the stress-surviving cells resume normal function is not known. We studied the in vivo impact of ER stress in terminally differentiating hypertrophic chondrocytes (HCs during endochondral bone formation. In transgenic mice expressing mutant collagen X as a consequence of a 13-base pair deletion in Col10a1 (13del, misfolded alpha1(X chains accumulate in HCs and elicit ERSS. Histological and gene expression analyses showed that these chondrocytes survived ER stress, but terminal differentiation is interrupted, and endochondral bone formation is delayed, producing a chondrodysplasia phenotype. This altered differentiation involves cell-cycle re-entry, the re-expression of genes characteristic of a prehypertrophic-like state, and is cell-autonomous. Concomitantly, expression of Col10a1 and 13del mRNAs are reduced, and ER stress is alleviated. ERSS, abnormal chondrocyte differentiation, and altered growth plate architecture also occur in mice expressing mutant collagen II and aggrecan. Alteration of the differentiation program in chondrocytes expressing unfolded or misfolded proteins may be part of an adaptive response that facilitates survival and recovery from the ensuing ER stress. However, the altered differentiation disrupts the highly coordinated events of endochondral ossification culminating in chondrodysplasia.

  9. Alteration, slope-classified alteration, and potential lahar inundation maps of volcanoes for the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Volcano Archive

    Science.gov (United States)

    Mars, John C.; Hubbard, Bernard E.; Pieri, David; Linick, Justin

    2015-01-01

    This study identifies areas prone to lahars from hydrothermally altered volcanic edifices on a global scale, using visible and near infrared (VNIR) and short wavelength infrared (SWIR) reflectance data from the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and digital elevation data from the ASTER Global Digital Elevation Model (GDEM) dataset. This is the first study to create a global database of hydrothermally altered volcanoes showing quantitatively compiled alteration maps and potentially affected drainages, as well as drainage-specific maps illustrating modeled lahars and their potential inundation zones. We (1) identified and prioritized 720 volcanoes based on population density surrounding the volcanoes using the Smithsonian Institution Global Volcanism Program database (GVP) and LandScan™ digital population dataset; (2) validated ASTER hydrothermal alteration mapping techniques using Airborne Visible and Infrared Imaging Spectrometer (AVIRIS) and ASTER data for Mount Shasta, California, and Pico de Orizaba (Citlaltépetl), Mexico; (3) mapped and slope-classified hydrothermal alteration using ASTER VNIR-SWIR reflectance data on 100 of the most densely populated volcanoes; (4) delineated drainages using ASTER GDEM data that show potential flow paths of possible lahars for the 100 mapped volcanoes; (5) produced potential alteration-related lahar inundation maps using the LAHARZ GIS code for Iztaccíhuatl, Mexico, and Mount Hood and Mount Shasta in the United States that illustrate areas likely to be affected based on DEM-derived volume estimates of hydrothermally altered rocks and the ~2x uncertainty factor inherent within a statistically-based lahar model; and (6) saved all image and vector data for 3D and 2D display in Google Earth™, ArcGIS® and other graphics display programs. In addition, these data are available from the ASTER Volcano Archive (AVA) for distribution (available at http://ava.jpl.nasa.gov/recent_alteration_zones.php).

  10. Altered Brain Functional Connectivity in Betel Quid-Dependent Chewers

    Directory of Open Access Journals (Sweden)

    Xiaojun Huang

    2017-11-01

    Full Text Available BackgroundBetel quid (BQ is a common psychoactive substance worldwide with particularly high usage in many Asian countries. This study aimed to explore the effect of BQ use on functional connectivity by comparing global functional brain networks and their subset between BQ chewers and healthy controls (HCs.MethodsResting-state functional magnetic resonance imaging (fMRI was obtained from 24 betel quid-dependent (BQD male chewers and 27 healthy male individuals on a 3.0T scanner. We used independent component analysis (ICA to determine components that represent the brain’s functional networks and their spatial aspects of functional connectivity. Two sample t-tests were used to identify the functional connectivity differences in each network between these two groups.ResultsSeventeen networks were identified by ICA. Nine of them showed connectivity differences between BQD and HCs (two sample t-tests, p < 0.001 uncorrected. We found increased functional connectivity in the orbitofrontal, bilateral frontoparietal, frontotemporal, occipital/parietal, frontotemporal/cerebellum, and temporal/limbic networks, and decreased connectivity in the parietal and medial frontal/anterior cingulate networks in the BQD compared to the HCs. The betel quid dependence scale scores were positively related to the increased functional connectivity in the orbitofrontal (r = 0.39, p = 0.03 while negatively related to the decreased functional connectivity in medial frontal/anterior cingulate networks (r = −0.35, p = 0.02.DiscussionOur findings provide further evidence that BQ chewing may lead to brain functional connectivity changes, which may play a key role in the psychological and physiological effects of BQ.

  11. Globalization as It Happens

    DEFF Research Database (Denmark)

    Flyverbom, Mikkel

    2012-01-01

    Globalization is usually understood as a structural, epochal condition altering the environment in which people, organizations, and societies operate. But such accounts offer little insight into the infrastructures, practices, and connections that facilitate the production of the global. This art......Globalization is usually understood as a structural, epochal condition altering the environment in which people, organizations, and societies operate. But such accounts offer little insight into the infrastructures, practices, and connections that facilitate the production of the global....... This article uses findings from an ethnographic study of tax planning to show how mundane practices and connectivities forge and organize global operations, and to argue for the value of analyzing processes of globalization in terms of assemblages and infrastructures. Empirically, the article captures how...... the making of ‘tax structures’ involves connecting, for instance, buildings in France, a human in Switzerland, a company in Denmark, various tax laws, a trust fund in New Zealand, and large amounts of money on the move. If studied along the lines of an analytics of ‘globalizing assemblages’, such financial...

  12. Global biodiversity, stoichiometry and ecosystem function responses to human-induced C-N-P imbalances.

    Science.gov (United States)

    Carnicer, Jofre; Sardans, Jordi; Stefanescu, Constantí; Ubach, Andreu; Bartrons, Mireia; Asensio, Dolores; Peñuelas, Josep

    2015-01-01

    Global change analyses usually consider biodiversity as a global asset that needs to be preserved. Biodiversity is frequently analysed mainly as a response variable affected by diverse environmental drivers. However, recent studies highlight that gradients of biodiversity are associated with gradual changes in the distribution of key dominant functional groups characterized by distinctive traits and stoichiometry, which in turn often define the rates of ecosystem processes and nutrient cycling. Moreover, pervasive links have been reported between biodiversity, food web structure, ecosystem function and species stoichiometry. Here we review current global stoichiometric gradients and how future distributional shifts in key functional groups may in turn influence basic ecosystem functions (production, nutrient cycling, decomposition) and therefore could exert a feedback effect on stoichiometric gradients. The C-N-P stoichiometry of most primary producers (phytoplankton, algae, plants) has been linked to functional trait continua (i.e. to major axes of phenotypic variation observed in inter-specific analyses of multiple traits). In contrast, the C-N-P stoichiometry of higher-level consumers remains less precisely quantified in many taxonomic groups. We show that significant links are observed between trait continua across trophic levels. In spite of recent advances, the future reciprocal feedbacks between key functional groups, biodiversity and ecosystem functions remain largely uncertain. The reported evidence, however, highlights the key role of stoichiometric traits and suggests the need of a progressive shift towards an ecosystemic and stoichiometric perspective in global biodiversity analyses. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. Altered functional connectivity within the central reward network in overweight and obese women

    Science.gov (United States)

    Coveleskie, K; Gupta, A; Kilpatrick, L A; Mayer, E D; Ashe-McNalley, C; Stains, J; Labus, J S; Mayer, E A

    2015-01-01

    Background/Objectives: Neuroimaging studies in obese subjects have identified abnormal activation of key regions of central reward circuits, including the nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to examine whether women with elevated body mass index (BMI) show structural and resting state (RS) functional connectivity alterations within regions of the reward network. Subjects/Methods: Fifty healthy, premenopausal women, 19 overweight and obese (high BMI=26–38 kg m−2) and 31 lean (BMI=19–25 kg m−2) were selected from the University of California Los Angeles' Oppenheimer Center for Neurobiology of Stress database. Structural and RS functional scans were collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation dynamics of intrinsic brain activity and functional connectivity of the NAcc to regions within the reward network were examined. Results: GMV of the left NAcc was significantly greater in the high BMI group than in the lean group (P=0.031). Altered frequency distributions were observed in women with high BMI compared with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and in bilateral anterior cingulate cortex (ACC) (P=0.014, ingestive behaviors. PMID:25599560

  14. Global convergence of periodic solution of neural networks with discontinuous activation functions

    International Nuclear Information System (INIS)

    Huang Lihong; Guo Zhenyuan

    2009-01-01

    In this paper, without assuming boundedness and monotonicity of the activation functions, we establish some sufficient conditions ensuring the existence and global asymptotic stability of periodic solution of neural networks with discontinuous activation functions by using the Yoshizawa-like theorem and constructing proper Lyapunov function. The obtained results improve and extend previous works.

  15. The Role of Low-severity Fire and Thermal Alteration of Soil Organic Matter in Carbon Preservation and GHG Flux From Global Peatlands

    Science.gov (United States)

    Flanagan, N. E.; Wang, H.; Hodgkins, S. B.; Richardson, C. J.

    2017-12-01

    Many global peatlands are dominated by fire-adapted plant communities and are subject to frequent wildfires with return intervals ranging between 3 to 100 years. Wildfires in peatlands are typically low-severity events that occur in winter and spring when vegetation is desiccated and soil moisture content is high. As a result, most wildfires consume aboveground fuels in a matter of minutes without igniting the nearly saturated peat. In such fires, surface soil layers are subjected to flash heating with a rapid loss of soil moisture but little loss of soil organic matter (SOM). Such fires have the potential to alter the chemical structure of SOM, even in the absence of combustion, through Maillard's Reaction and similar chemical processes, and through structural changes that protect SOM from decomposition. This study examines the effects of low-intensity surface fires on the recalcitrance of SOM from fire-adapted communities located in subtropical, temperate and sub-boreal peatlands. In addition, soil from a non-fire-adapted Peruvian palm peatland was examined for response to thermal alteration. The timing and temperatures of low-intensity fires were measured in the field during prescribed burns and replicated in simulated fires. The effects of fire on the chemical structure of SOM were examined with FTIR, SEM and XPS. Burned and unburned peat replicates were incubated at three temperatures (5oC, 15oC, 25oC) in controlled chambers for more than six months. Burned replicates initially showed higher CO2, CH4 and NO2 emissions. Yet, within four weeks emissions from the burned replicates dropped below those of unburned replicates and remained significantly lower (10-50%) for the duration of the experiment. In addition, thermal alteration significantly reduced the temperature sensitivity (Q10) of thermally altered peat. After accounting for small initial losses of organic matter (<10 %) during the fire simulations, thermal alteration of SOM resulted in a net long

  16. Global and local curvature in density functional theory.

    Science.gov (United States)

    Zhao, Qing; Ioannidis, Efthymios I; Kulik, Heather J

    2016-08-07

    Piecewise linearity of the energy with respect to fractional electron removal or addition is a requirement of an electronic structure method that necessitates the presence of a derivative discontinuity at integer electron occupation. Semi-local exchange-correlation (xc) approximations within density functional theory (DFT) fail to reproduce this behavior, giving rise to deviations from linearity with a convex global curvature that is evidence of many-electron, self-interaction error and electron delocalization. Popular functional tuning strategies focus on reproducing piecewise linearity, especially to improve predictions of optical properties. In a divergent approach, Hubbard U-augmented DFT (i.e., DFT+U) treats self-interaction errors by reducing the local curvature of the energy with respect to electron removal or addition from one localized subshell to the surrounding system. Although it has been suggested that DFT+U should simultaneously alleviate global and local curvature in the atomic limit, no detailed study on real systems has been carried out to probe the validity of this statement. In this work, we show when DFT+U should minimize deviations from linearity and demonstrate that a "+U" correction will never worsen the deviation from linearity of the underlying xc approximation. However, we explain varying degrees of efficiency of the approach over 27 octahedral transition metal complexes with respect to transition metal (Sc-Cu) and ligand strength (CO, NH3, and H2O) and investigate select pathological cases where the delocalization error is invisible to DFT+U within an atomic projection framework. Finally, we demonstrate that the global and local curvatures represent different quantities that show opposing behavior with increasing ligand field strength, and we identify where these two may still coincide.

  17. Thermal Stimulation Alters Cervical Spinal Cord Functional Connectivity in Humans.

    Science.gov (United States)

    Weber, Kenneth A; Sentis, Amy I; Bernadel-Huey, Olivia N; Chen, Yufen; Wang, Xue; Parrish, Todd B; Mackey, Sean

    2018-01-15

    The spinal cord has an active role in the modulation and transmission of the neural signals traveling between the body and the brain. Recent advancements in functional magnetic resonance imaging (fMRI) have made the in vivo examination of spinal cord function in humans now possible. This technology has been recently extended to the investigation of resting state functional networks in the spinal cord, leading to the identification of distinct patterns of spinal cord functional connectivity. In this study, we expand on the previous work and further investigate resting state cervical spinal cord functional connectivity in healthy participants (n = 15) using high resolution imaging coupled with both seed-based functional connectivity analyses and graph theory-based metrics. Within spinal cord segment functional connectivity was present between the left and right ventral horns (bilateral motor network), left and right dorsal horns (bilateral sensory network), and the ipsilateral ventral and dorsal horns (unilateral sensory-motor network). Functional connectivity between the spinal cord segments was less apparent with the connectivity centered at the region of interest and spanning spinal cord functional network was demonstrated to be state-dependent as thermal stimulation of the right ventrolateral forearm resulted in significant disruption of the bilateral sensory network, increased network global efficiency, and decreased network modularity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Altered functional connectivity of the dorsolateral prefrontal cortex in first-episode patients with major depressive disorder

    International Nuclear Information System (INIS)

    Ye, Ting; Peng, Jing; Nie, Binbin; Gao, Juan; Liu, Jiangtao; Li, Yang; Wang, Gang; Ma, Xin; Li, Kuncheng

    2012-01-01

    Background: The aim of this study was to investigate resting-state functional connectivity alteration of the right dorsolateral prefrontal cortex (DLPFC) in patients with first-episode major depressive disorder (MDD). Methods: Twenty-two first-episode MDD patients and thirty age-, gender- and education-matched healthy control subjects were enrolled. Rest state functional magnetic resonance images and structure magnetic resonance images were scanned. The functional connectivity analysis was done based on the result of voxel-based morphometry (VBM). And the right DLPFC was chosen as the seed region of interests (ROI), as its gray matter density (GMD) decreased in the MDD patients compared with controls and its GMD values were negative correlation with the Hamilton Depression Rating Scale (HDRS) scores. Results: Compared to healthy controls, the MDD patients showed increased functional connectivity with right the DLPFC in the left dorsal anterior cingulate cortex (ACC), left parahippocampal gyrus (PHG), thalamus and precentral gyrus. In contrast, there were decreased functional connectivity between the right DLPFC and right parietal lobe. Conclusions: By applying the VBM results to the functional connectivity analysis, the study suggested that abnormality of GMD in right DLPFC might be related to the functional connectivity alteration in the pathophysiology of MDD, which might be useful in further characterizing structure–function relations in this disorder.

  19. Altered functional connectivity of the dorsolateral prefrontal cortex in first-episode patients with major depressive disorder

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Ting, E-mail: yeting@ihep.ac.cn [Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Graduate School of Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Peng, Jing, E-mail: ppengjjing@sina.com.cn [Department of Radiology, Xuanwu Hospital of Capital Medical University, No. 45, Chang-Chun St, Xuanwu District, Beijing 100053 (China); Nie, Binbin, E-mail: niebb@ihep.ac.cn [Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Gao, Juan, E-mail: gaojuan@ihep.ac.cn [Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Graduate School of Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Liu, Jiangtao, E-mail: Liujiangtao813@sina.com [Department of Radiology, Xuanwu Hospital of Capital Medical University, No. 45, Chang-Chun St, Xuanwu District, Beijing 100053 (China); Li, Yang, E-mail: Liyang2007428@hotmail.com [Department of Psychiatry, Anding Hospital of Capital Medical University, No. 5, An Kang Hutong, Deshengmen wai, Xicheng District, Beijing 100088 (China); Wang, Gang, E-mail: gangwang@gmail.com [Department of Psychiatry, Anding Hospital of Capital Medical University, No. 5, An Kang Hutong, Deshengmen wai, Xicheng District, Beijing 100088 (China); Ma, Xin, E-mail: lijianshe@medmail.com.cn [Department of Psychiatry, Anding Hospital of Capital Medical University, No. 5, An Kang Hutong, Deshengmen wai, Xicheng District, Beijing 100088 (China); Li, Kuncheng [Department of Radiology, Xuanwu Hospital of Capital Medical University, No. 45, Chang-Chun St, Xuanwu District, Beijing 100053 (China); and others

    2012-12-15

    Background: The aim of this study was to investigate resting-state functional connectivity alteration of the right dorsolateral prefrontal cortex (DLPFC) in patients with first-episode major depressive disorder (MDD). Methods: Twenty-two first-episode MDD patients and thirty age-, gender- and education-matched healthy control subjects were enrolled. Rest state functional magnetic resonance images and structure magnetic resonance images were scanned. The functional connectivity analysis was done based on the result of voxel-based morphometry (VBM). And the right DLPFC was chosen as the seed region of interests (ROI), as its gray matter density (GMD) decreased in the MDD patients compared with controls and its GMD values were negative correlation with the Hamilton Depression Rating Scale (HDRS) scores. Results: Compared to healthy controls, the MDD patients showed increased functional connectivity with right the DLPFC in the left dorsal anterior cingulate cortex (ACC), left parahippocampal gyrus (PHG), thalamus and precentral gyrus. In contrast, there were decreased functional connectivity between the right DLPFC and right parietal lobe. Conclusions: By applying the VBM results to the functional connectivity analysis, the study suggested that abnormality of GMD in right DLPFC might be related to the functional connectivity alteration in the pathophysiology of MDD, which might be useful in further characterizing structure–function relations in this disorder.

  20. Global optimization applied to GPS positioning by ambiguity functions

    International Nuclear Information System (INIS)

    Baselga, Sergio

    2010-01-01

    Differential GPS positioning with carrier-phase observables is commonly done in a process that involves determination of the unknown integer ambiguity values. An alternative approach, named the ambiguity function method, was already proposed in the early days of GPS positioning. By making use of a trigonometric function ambiguity unknowns are eliminated from the functional model before the estimation process. This approach has significant advantages, such as ease of use and insensitivity to cycle slips, but requires such high accuracy in the initial approximate coordinates that its use has been practically dismissed from consideration. In this paper a novel strategy is proposed so that the need for highly accurate initial coordinates disappears: the application of a global optimization method to the ambiguity functions model. The use of this strategy enables the ambiguity function method to compete with the present prevailing approach of ambiguity resolution

  1. Integrating abundance and functional traits reveals new global hotspots of fish diversity.

    Science.gov (United States)

    Stuart-Smith, Rick D; Bates, Amanda E; Lefcheck, Jonathan S; Duffy, J Emmett; Baker, Susan C; Thomson, Russell J; Stuart-Smith, Jemina F; Hill, Nicole A; Kininmonth, Stuart J; Airoldi, Laura; Becerro, Mikel A; Campbell, Stuart J; Dawson, Terence P; Navarrete, Sergio A; Soler, German A; Strain, Elisabeth M A; Willis, Trevor J; Edgar, Graham J

    2013-09-26

    Species richness has dominated our view of global biodiversity patterns for centuries. The dominance of this paradigm is reflected in the focus by ecologists and conservation managers on richness and associated occurrence-based measures for understanding drivers of broad-scale diversity patterns and as a biological basis for management. However, this is changing rapidly, as it is now recognized that not only the number of species but the species present, their phenotypes and the number of individuals of each species are critical in determining the nature and strength of the relationships between species diversity and a range of ecological functions (such as biomass production and nutrient cycling). Integrating these measures should provide a more relevant representation of global biodiversity patterns in terms of ecological functions than that provided by simple species counts. Here we provide comparisons of a traditional global biodiversity distribution measure based on richness with metrics that incorporate species abundances and functional traits. We use data from standardized quantitative surveys of 2,473 marine reef fish species at 1,844 sites, spanning 133 degrees of latitude from all ocean basins, to identify new diversity hotspots in some temperate regions and the tropical eastern Pacific Ocean. These relate to high diversity of functional traits amongst individuals in the community (calculated using Rao's Q), and differ from previously reported patterns in functional diversity and richness for terrestrial animals, which emphasize species-rich tropical regions only. There is a global trend for greater evenness in the number of individuals of each species, across the reef fish species observed at sites ('community evenness'), at higher latitudes. This contributes to the distribution of functional diversity hotspots and contrasts with well-known latitudinal gradients in richness. Our findings suggest that the contribution of species diversity to a range of

  2. Modelling altered revenue function based on varying power consumption distribution and electricity tariff charge using data analytics framework

    Science.gov (United States)

    Zainudin, W. N. R. A.; Ramli, N. A.

    2017-09-01

    In 2010, Energy Commission (EC) had introduced Incentive Based Regulation (IBR) to ensure sustainable Malaysian Electricity Supply Industry (MESI), promotes transparent and fair returns, encourage maximum efficiency and maintains policy driven end user tariff. To cater such revolutionary transformation, a sophisticated system to generate policy driven electricity tariff structure is in great need. Hence, this study presents a data analytics framework that generates altered revenue function based on varying power consumption distribution and tariff charge function. For the purpose of this study, the power consumption distribution is being proxy using proportion of household consumption and electricity consumed in KwH and the tariff charge function is being proxy using three-tiered increasing block tariff (IBT). The altered revenue function is useful to give an indication on whether any changes in the power consumption distribution and tariff charges will give positive or negative impact to the economy. The methodology used for this framework begins by defining the revenue to be a function of power consumption distribution and tariff charge function. Then, the proportion of household consumption and tariff charge function is derived within certain interval of electricity power. Any changes in those proportion are conjectured to contribute towards changes in revenue function. Thus, these changes can potentially give an indication on whether the changes in power consumption distribution and tariff charge function are giving positive or negative impact on TNB revenue. Based on the finding of this study, major changes on tariff charge function seems to affect altered revenue function more than power consumption distribution. However, the paper concludes that power consumption distribution and tariff charge function can influence TNB revenue to some great extent.

  3. Altered resting-state functional connectivity in patients with chronic bilateral vestibular failure

    OpenAIRE

    Martin Göttlich; Nico M. Jandl; Jann F. Wojak; Andreas Sprenger; Janina von der Gablentz; Thomas F. Münte; Ulrike M. Krämer; Christoph Helmchen

    2014-01-01

    Patients with bilateral vestibular failure (BVF) suffer from gait unsteadiness, oscillopsia and impaired spatial orientation. Brain imaging studies applying caloric irrigation to patients with BVF have shown altered neural activity of cortical visual–vestibular interaction: decreased bilateral neural activity in the posterior insula and parietal operculum and decreased deactivations in the visual cortex. It is unknown how this affects functional connectivity in the resting brain and how chang...

  4. Finsler metrics—a global approach with applications to geometric function theory

    CERN Document Server

    Abate, Marco

    1994-01-01

    Complex Finsler metrics appear naturally in complex analysis. To develop new tools in this area, the book provides a graduate-level introduction to differential geometry of complex Finsler metrics. After reviewing real Finsler geometry stressing global results, complex Finsler geometry is presented introducing connections, Kählerianity, geodesics, curvature. Finally global geometry and complex Monge-Ampère equations are discussed for Finsler manifolds with constant holomorphic curvature, which are important in geometric function theory. Following E. Cartan, S.S. Chern and S. Kobayashi, the global approach carries the full strength of hermitian geometry of vector bundles avoiding cumbersome computations, and thus fosters applications in other fields.

  5. Protein-energy malnutrition alters thermoregulatory homeostasis and the response to brain ischemia.

    Science.gov (United States)

    Smith, Shari E; Prosser-Loose, Erin J; Colbourne, Frederick; Paterson, Phyllis G

    2011-02-01

    Co-existing protein-energy malnutrition (PEM), characterized by deficits in both protein and energy status, impairs functional outcome following global ischemia and has been associated with increased reactive gliosis. Since temperature is a key determinant of brain damage following an ischemic insult, the objective was to investigate whether alterations in post-ischemic temperature regulation contribute to PEM-induced reactive gliosis following ischemia. Male Sprague-Dawley rats (190-280 g) were assigned to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7 days prior to either global ischemia or sham surgery. There was a rapid disruption in thermoregulatory function in rats fed the low protein diet as assessed by continuous recording of core temperature with bio-electrical sensor transmitters. Both daily temperature fluctuation and mean temperature increased within the first 24 hours, and these remained significantly elevated throughout the 7 day pre-ischemic period (p protein diet rapidly impairs the ability to maintain thermoregulatory homeostasis, and the resultant PEM also diminishes the ability to thermoregulate in response to a challenge. Since temperature regulation is a key determinant of brain injury following ischemia, these findings suggest that the pathophysiology of brain injury could be altered in stroke victims with coexisting PEM.

  6. Will Global Climate Change Alter Fundamental Human Immune Reactivity: Implications for Child Health?

    Science.gov (United States)

    Swaminathan, Ashwin; Lucas, Robyn M; Harley, David; McMichael, Anthony J

    2014-11-11

    The human immune system is an interface across which many climate change sensitive exposures can affect health outcomes. Gaining an understanding of the range of potential effects that climate change could have on immune function will be of considerable importance, particularly for child health, but has, as yet, received minimal research attention. We postulate several mechanisms whereby climate change sensitive exposures and conditions will subtly impair aspects of the human immune response, thereby altering the distribution of vulnerability within populations-particularly for children-to infection and disease. Key climate change-sensitive pathways include under-nutrition, psychological stress and exposure to ambient ultraviolet radiation, with effects on susceptibility to infection, allergy and autoimmune diseases. Other climate change sensitive exposures may also be important and interact, either additively or synergistically, to alter health risks. Conducting directed research in this area is imperative as the potential public health implications of climate change-induced weakening of the immune system at both individual and population levels are profound. This is particularly relevant for the already vulnerable children of the developing world, who will bear a disproportionate burden of future adverse environmental and geopolitical consequences of climate change.

  7. Will Global Climate Change Alter Fundamental Human Immune Reactivity: Implications for Child Health?

    Directory of Open Access Journals (Sweden)

    Ashwin Swaminathan

    2014-11-01

    Full Text Available The human immune system is an interface across which many climate change sensitive exposures can affect health outcomes. Gaining an understanding of the range of potential effects that climate change could have on immune function will be of considerable importance, particularly for child health, but has, as yet, received minimal research attention. We postulate several mechanisms whereby climate change sensitive exposures and conditions will subtly impair aspects of the human immune response, thereby altering the distribution of vulnerability within populations—particularly for children—to infection and disease. Key climate change-sensitive pathways include under-nutrition, psychological stress and exposure to ambient ultraviolet radiation, with effects on susceptibility to infection, allergy and autoimmune diseases. Other climate change sensitive exposures may also be important and interact, either additively or synergistically, to alter health risks. Conducting directed research in this area is imperative as the potential public health implications of climate change-induced weakening of the immune system at both individual and population levels are profound. This is particularly relevant for the already vulnerable children of the developing world, who will bear a disproportionate burden of future adverse environmental and geopolitical consequences of climate change.

  8. Gene expression alterations associated with outcome in aromatase inhibitor-treated ER+ early-stage breast cancer patients

    DEFF Research Database (Denmark)

    Gravgaard Thomsen, Karina Hedelund; Lyng, Maria Bibi; Elias, Daniel

    2015-01-01

    predictive of outcome of ER+ breast cancer patients treated with AIs are needed. Global gene expression analysis was performed on ER+ primary breast cancers from patients treated with adjuvant AI monotherapy; half experienced recurrence (median follow-up 6.7 years). Gene expression alterations were validated...... by qRT-PCR, and functional studies evaluating the effect of siRNA-mediated gene knockdown on cell growth were performed. Twenty-six genes, including TFF3, DACH1, RGS5, and GHR, were shown to exhibit altered expression in tumors from patients with recurrence versus non-recurrent (fold change ≥1.5, p ....05), and the gene expression alterations were confirmed using qRT-PCR. Ten of these 26 genes could be linked in a network associated with cellular proliferation, growth, and development. TFF3, which encodes for trefoil factor 3 and is an estrogen-responsive oncogene shown to play a functional role in tamoxifen...

  9. Impaired small-world network efficiency and dynamic functional distribution in patients with cirrhosis.

    Directory of Open Access Journals (Sweden)

    Tun-Wei Hsu

    Full Text Available Hepatic encephalopathy (HE is a complex neuropsychiatric syndrome and a major complication of liver cirrhosis. Dysmetabolism of the brain, related to elevated ammonia levels, interferes with intercortical connectivity and cognitive function. For evaluation of network efficiency, a 'small-world' network model can quantify the effectiveness of information transfer within brain networks. This study aimed to use small-world topology to investigate abnormalities of neuronal connectivity among widely distributed brain regions in patients with liver cirrhosis using resting-state functional magnetic resonance imaging (rs-fMRI. Seventeen cirrhotic patients without HE, 9 with minimal HE, 9 with overt HE, and 35 healthy controls were compared. The interregional correlation matrix was obtained by averaging the rs-fMRI time series over all voxels in each of the 90 regions using the automated anatomical labeling model. Cost and correlation threshold values were then applied to construct the functional brain network. The absolute and relative network efficiencies were calculated; quantifying distinct aspects of the local and global topological network organization. Correlations between network topology parameters, ammonia levels, and the severity of HE were determined using linear regression and ANOVA. The local and global topological efficiencies of the functional connectivity network were significantly disrupted in HE patients; showing abnormal small-world properties. Alterations in regional characteristics, including nodal efficiency and nodal strength, occurred predominantly in the association, primary, and limbic/paralimbic regions. The degree of network organization disruption depended on the severity of HE. Ammonia levels were also significantly associated with the alterations in local network properties. Results indicated that alterations in the rs-fMRI network topology of the brain were associated with HE grade; and that focal or diffuse lesions

  10. Ion Channel Genes and Epilepsy: Functional Alteration, Pathogenic Potential, and Mechanism of Epilepsy.

    Science.gov (United States)

    Wei, Feng; Yan, Li-Min; Su, Tao; He, Na; Lin, Zhi-Jian; Wang, Jie; Shi, Yi-Wu; Yi, Yong-Hong; Liao, Wei-Ping

    2017-08-01

    Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsy-associated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations (funotypes), and phenotypes of these mutations. Eleven genes featured loss-of-function mutations and six had gain-of-function mutations. Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.

  11. Altered Cerebral Blood Flow Covariance Network in Schizophrenia.

    Science.gov (United States)

    Liu, Feng; Zhuo, Chuanjun; Yu, Chunshui

    2016-01-01

    Many studies have shown abnormal cerebral blood flow (CBF) in schizophrenia; however, it remains unclear how topological properties of CBF network are altered in this disorder. Here, arterial spin labeling (ASL) MRI was employed to measure resting-state CBF in 96 schizophrenia patients and 91 healthy controls. CBF covariance network of each group was constructed by calculating across-subject CBF covariance between 90 brain regions. Graph theory was used to compare intergroup differences in global and nodal topological measures of the network. Both schizophrenia patients and healthy controls had small-world topology in CBF covariance networks, implying an optimal balance between functional segregation and integration. Compared with healthy controls, schizophrenia patients showed reduced small-worldness, normalized clustering coefficient and local efficiency of the network, suggesting a shift toward randomized network topology in schizophrenia. Furthermore, schizophrenia patients exhibited altered nodal centrality in the perceptual-, affective-, language-, and spatial-related regions, indicating functional disturbance of these systems in schizophrenia. This study demonstrated for the first time that schizophrenia patients have disrupted topological properties in CBF covariance network, which provides a new perspective (efficiency of blood flow distribution between brain regions) for understanding neural mechanisms of schizophrenia.

  12. Altered effect of dopamine transporter 3'UTR VNTR genotype on prefrontal and striatal function in schizophrenia.

    Science.gov (United States)

    Prata, Diana P; Mechelli, Andrea; Picchioni, Marco M; Fu, Cynthia H Y; Toulopoulou, Timothea; Bramon, Elvira; Walshe, Muriel; Murray, Robin M; Collier, David A; McGuire, Philip

    2009-11-01

    The dopamine transporter plays a key role in the regulation of central dopaminergic transmission, which modulates cognitive processing. Disrupted dopamine function and impaired executive processing are robust features of schizophrenia. To examine the effect of a polymorphism in the dopamine transporter gene (the variable number of tandem repeats in the 3' untranslated region) on brain function during executive processing in healthy volunteers and patients with schizophrenia. We hypothesized that this variation would have a different effect on prefrontal and striatal activation in schizophrenia, reflecting altered dopamine function. Case-control study. Psychiatric research center. Eighty-five subjects, comprising 44 healthy volunteers (18 who were 9-repeat carriers and 26 who were 10-repeat homozygotes) and 41 patients with DSM-IV schizophrenia (18 who were 9-repeat carriers and 23 who were 10-repeat homozygotes). Regional brain activation during word generation relative to repetition in an overt verbal fluency task measured by functional magnetic resonance imaging. Main effects of genotype and diagnosis on activation and their interaction were estimated with analysis of variance in SPM5. Irrespective of diagnosis, the 10-repeat allele was associated with greater activation than the 9-repeat allele in the left anterior insula and right caudate nucleus. Trends for the same effect in the right insula and for greater deactivation in the rostral anterior cingulate cortex were also detected. There were diagnosis x genotype interactions in the left middle frontal gyrus and left nucleus accumbens, where the 9-repeat allele was associated with greater activation than the 10-repeat allele in patients but not controls. Insular, cingulate, and striatal function during an executive task is normally modulated by variation in the dopamine transporter gene. Its effect on activation in the dorsolateral prefrontal cortex and ventral striatum is altered in patients with schizophrenia

  13. Euclidean scalar Green function in a higher dimensional global monopole space-time

    International Nuclear Information System (INIS)

    Bezerra de Mello, E.R.

    2002-01-01

    We construct the explicit Euclidean scalar Green function associated with a massless field in a higher dimensional global monopole space-time, i.e., a (1+d)-space-time with d≥3 which presents a solid angle deficit. Our result is expressed in terms of an infinite sum of products of Legendre functions with Gegenbauer polynomials. Although this Green function cannot be expressed in a closed form, for the specific case where the solid angle deficit is very small, it is possible to develop the sum and obtain the Green function in a more workable expression. Having this expression it is possible to calculate the vacuum expectation value of some relevant operators. As an application of this formalism, we calculate the renormalized vacuum expectation value of the square of the scalar field, 2 (x)> Ren , and the energy-momentum tensor, μν (x)> Ren , for the global monopole space-time with spatial dimensions d=4 and d=5

  14. Whole-brain structural topology in adult attention-deficit/hyperactivity disorder: Preserved global - disturbed local network organization.

    Science.gov (United States)

    Sidlauskaite, Justina; Caeyenberghs, Karen; Sonuga-Barke, Edmund; Roeyers, Herbert; Wiersema, Jan R

    2015-01-01

    Prior studies demonstrate altered organization of functional brain networks in attention-deficit/hyperactivity disorder (ADHD). However, the structural underpinnings of these functional disturbances are poorly understood. In the current study, we applied a graph-theoretic approach to whole-brain diffusion magnetic resonance imaging data to investigate the organization of structural brain networks in adults with ADHD and unaffected controls using deterministic fiber tractography. Groups did not differ in terms of global network metrics - small-worldness, global efficiency and clustering coefficient. However, there were widespread ADHD-related effects at the nodal level in relation to local efficiency and clustering. The affected nodes included superior occipital, supramarginal, superior temporal, inferior parietal, angular and inferior frontal gyri, as well as putamen, thalamus and posterior cerebellum. Lower local efficiency of left superior temporal and supramarginal gyri was associated with higher ADHD symptom scores. Also greater local clustering of right putamen and lower local clustering of left supramarginal gyrus correlated with ADHD symptom severity. Overall, the findings indicate preserved global but altered local network organization in adult ADHD implicating regions underpinning putative ADHD-related neuropsychological deficits.

  15. ALTER-GLOBALISM AND DEVELOPMENT IN MIGRATION CONDITIONS. THE CASE OF AN EAST EUROPEAN COUNTRY

    Directory of Open Access Journals (Sweden)

    Alina HALLER

    2017-12-01

    Full Text Available Globalisation is a process that brings advantages and disadvantages to all states, regardless of their stage of development. The relative deprivation, especially the financial one, of the developing countries is a reason of frustration, which motivates the emigration decision; hence our orientation to alter-globalism. In this paper, I intend to highlight by means of analysis, synthesis, deduction, induction, and statistic data, the causes and types of migration in Romania’s case, one of the main European countries where the immigrants originate from. We will see how globalisation manifests itself in a twofold manner in the economy and the society of a developing country, just like migration. We will show why a poor country is avoided by immigrants and deserted, as a result of immigration, by its own population, while, just like the developed states, it is likely to face the same demographic, economic and social problems, considering that the process of demographic transition is already manifested.

  16. Altered myofilament structure and function in dogs with Duchenne muscular dystrophy cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ait Mou, Younss; Lacampagne, Alain; Irving, Thomas; Scheuermann, Valérie; Blot, Stéphane; Ghaleh, Bijan; de Tombe, Pieter P.; Cazorla, Olivier

    2018-01-01

    Aim Duchenne Muscular Dystrophy (DMD) is associated with progressive depressed left ventricular (LV) function. However, DMD effects on myofilament structure and function are poorly understood. Golden Retriever Muscular Dystrophy (GRMD) is a dog model of DMD recapitulating the human form of DMD. Objective The objective of this study is to evaluate myofilament structure and function alterations in GRMD model with spontaneous cardiac failure. Methods and results We have employed synchrotron X-rays diffraction to evaluate myofilament lattice spacing at various sarcomere lengths (SL) on permeabilized LV myocardium. We found a negative correlation between SL and lattice spacing in both sub-epicardium (EPI) and sub-endocardium (ENDO) LV layers in control dog hearts. In the ENDO of GRMD hearts this correlation is steeper due to higher lattice spacing at short SL (1.9 μm). Furthermore, cross-bridge cycling indexed by the kinetics of tension redevelopment (ktr) was faster in ENDO GRMD myofilaments at short SL. We measured post-translational modifications of key regulatory contractile proteins. S-glutathionylation of cardiac Myosin Binding Protein-C (cMyBP-C) was unchanged and PKA dependent phosphorylation of the cMyBP-C was significantly reduced in GRMD ENDO tissue and more modestly in EPI tissue. Conclusions We found a gradient of contractility in control dogs' myocardium that spreads across the LV wall, negatively correlated with myofilament lattice spacing. Chronic stress induced by dystrophin deficiency leads to heart failure that is tightly associated with regional structural changes indexed by increased myofilament lattice spacing, reduced phosphorylation of regulatory proteins and altered myofilament contractile properties in GRMD dogs.

  17. A New Filled Function Method with One Parameter for Global Optimization

    Directory of Open Access Journals (Sweden)

    Fei Wei

    2013-01-01

    Full Text Available The filled function method is an effective approach to find the global minimizer of multidimensional multimodal functions. The conventional filled functions are numerically unstable due to exponential or logarithmic term and sensitive to parameters. In this paper, a new filled function with only one parameter is proposed, which is continuously differentiable and proved to satisfy all conditions of the filled function definition. Moreover, this filled function is not sensitive to parameter, and the overflow can not happen for this function. Based on these, a new filled function method is proposed, and it is numerically stable to the initial point and the parameter variable. The computer simulations indicate that the proposed filled function method is efficient and effective.

  18. Altered Primary Motor Cortex Structure, Organization, and Function in Chronic Pain: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Chang, Wei-Ju; O'Connell, Neil E; Beckenkamp, Paula R; Alhassani, Ghufran; Liston, Matthew B; Schabrun, Siobhan M

    2018-04-01

    Chronic pain can be associated with movement abnormalities. The primary motor cortex (M1) has an essential role in the formulation and execution of movement. A number of changes in M1 function have been reported in studies of people with chronic pain. This review systematically evaluated the evidence for altered M1 structure, organization, and function in people with chronic pain of neuropathic and non-neuropathic origin. Database searches were conducted and a modified STrengthening the Reporting of OBservational studies in Epidemiology checklist was used to assess the methodological quality of included studies. Meta-analyses, including preplanned subgroup analyses on the basis of condition were performed where possible. Sixty-seven studies (2,290 participants) using various neurophysiological measures were included. There is conflicting evidence of altered M1 structure, organization, and function for neuropathic and non-neuropathic pain conditions. Meta-analyses provided evidence of increased M1 long-interval intracortical inhibition in chronic pain populations. For most measures, the evidence of M1 changes in chronic pain populations is inconclusive. This review synthesizes the evidence of altered M1 structure, organization, and function in chronic pain populations. For most measures, M1 changes are inconsistent between studies and more research with larger samples and rigorous methodology is required to elucidate M1 changes in chronic pain populations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. A Surfactant-Induced Functional Modulation of a Global Virulence Regulator from Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Sukhendu Mandal

    Full Text Available Triton X-100 (TX-100, a useful non-ionic surfactant, reduced the methicillin resistance in Staphylococcus aureus significantly. Many S. aureus proteins were expressed in the presence of TX-100. SarA, one of the TX-100-induced proteins, acts as a global virulence regulator in S. aureus. To understand the effects of TX-100 on the structure, and function of SarA, a recombinant S. aureus SarA (rSarA and its derivative (C9W have been investigated in the presence of varying concentrations of this surfactant using various probes. Our data have revealed that both rSarA and C9W bind to the cognate DNA with nearly similar affinity in the absence of TX-100. Interestingly, their DNA binding activities have been significantly increased in the presence of pre-micellar concentration of TX-100. The increase of TX-100 concentrations to micellar or post-micellar concentration did not greatly enhance their activities further. TX-100 molecules have altered the secondary and tertiary structures of both proteins to some extents. Size of the rSarA-TX-100 complex appears to be intermediate to those of rSarA and TX-100. Additional analyses show a relatively moderate interaction between C9W and TX-100. Binding of TX-100 to C9W has, however, occurred by a cooperative pathway particularly at micellar and higher concentrations of this surfactant. Taken together, TX-100-induced structural alteration of rSarA and C9W might be responsible for their increased DNA binding activity. As TX-100 has stabilized the somewhat weaker SarA-DNA complex effectively, it could be used to study its structure in the future.

  20. Biocrusts in the context of global change

    Science.gov (United States)

    Reed, Sasha C.; Maestre, Fernando T.; Ochoa-Hueso, Raul; Kuske, Cheryl; Darrouzet-Nardi, Anthony N.; Darby, Brian; Sinsabaugh, Bob; Oliver, Mel; Sancho, Leo; Belnap, Jayne

    2016-01-01

    A wide range of studies show global environmental change will profoundly affect the structure, function, and dynamics of terrestrial ecosystems. The research synthesized here underscores that biocrust communities are also likely to respond significantly to global change drivers, with a large potential for modification to their abundance, composition, and function. We examine how elevated atmospheric CO2 concentrations, climate change (increased temperature and altered precipitation), and nitrogen deposition affect biocrusts and the ecosystems they inhabit. We integrate experimental and observational data, as well as physiological, community ecology, and biogeochemical perspectives. Taken together, these data highlight the potential for biocrust organisms to respond dramatically to environmental change and show how changes to biocrust community composition translate into effects on ecosystem function (e.g., carbon and nutrient cycling, soil stability, energy balance). Due to the importance of biocrusts in regulating dryland ecosystem processes and the potential for large modifications to biocrust communities, an improved understanding and predictive capacity regarding biocrust responses to environmental change are of scientific and societal relevance.

  1. Altered Brain Functional Connectome in Migraine with and without Restless Legs Syndrome: A Resting-State Functional MRI Study

    Directory of Open Access Journals (Sweden)

    Fu-Chi Yang

    2018-01-01

    Full Text Available BackgroundMigraine is frequently comorbid with restless legs syndrome (RLS, both displaying functional connectivity (FC alterations in multiple brain networks, although the neurological basis of this association is unknown.MethodsWe performed resting-state functional magnetic resonance imaging and network-wise analysis of FC in migraine patients with and without RLS and healthy controls (CRL. Network-based statistics (NBS and composite FC matrix analyses were performed to identify the patterns of FC changes. Correlation analyses were performed to identify associations between alterations in FC and clinical profiles.ResultsNBS results revealed that both migraine patients with and without RLS exhibited lower FC than CRL in the dorsal attention, salience, default mode, cingulo-opercular, visual, frontoparietal, auditory, and sensory/somatomotor networks. Further composite FC matrix analyses revealed differences in FC of the salience, default mode to subcortical and frontoparietal, auditory to salience, and memory retrieval networks between migraine patients with and without RLS. There was a trend toward a negative association between RLS severity and cross-network abnormalities in the default mode to subcortical network.DiscussionMigraine patients with and without RLS exhibit disruptions of brain FC. Such findings suggest that these disorders are associated with differential neuropathological mechanisms and may aid in the future development of neuroimaging-driven biomarkers for these conditions.

  2. Elevation alters ecosystem properties across temperate treelines globally

    Science.gov (United States)

    Mayor, Jordan R.; Sanders, Nathan J.; Classen, Aimée T.; Bardgett, Richard D.; Clément, Jean-Christophe; Fajardo, Alex; Lavorel, Sandra; Sundqvist, Maja K.; Bahn, Michael; Chisholm, Chelsea; Cieraad, Ellen; Gedalof, Ze'Ev; Grigulis, Karl; Kudo, Gaku; Oberski, Daniel L.; Wardle, David A.

    2017-01-01

    Temperature is a primary driver of the distribution of biodiversity as well as of ecosystem boundaries. Declining temperature with increasing elevation in montane systems has long been recognized as a major factor shaping plant community biodiversity, metabolic processes, and ecosystem dynamics. Elevational gradients, as thermoclines, also enable prediction of long-term ecological responses to climate warming. One of the most striking manifestations of increasing elevation is the abrupt transitions from forest to treeless alpine tundra. However, whether there are globally consistent above- and belowground responses to these transitions remains an open question. To disentangle the direct and indirect effects of temperature on ecosystem properties, here we evaluate replicate treeline ecotones in seven temperate regions of the world. We find that declining temperatures with increasing elevation did not affect tree leaf nutrient concentrations, but did reduce ground-layer community-weighted plant nitrogen, leading to the strong stoichiometric convergence of ground-layer plant community nitrogen to phosphorus ratios across all regions. Further, elevation-driven changes in plant nutrients were associated with changes in soil organic matter content and quality (carbon to nitrogen ratios) and microbial properties. Combined, our identification of direct and indirect temperature controls over plant communities and soil properties in seven contrasting regions suggests that future warming may disrupt the functional properties of montane ecosystems, particularly where plant community reorganization outpaces treeline advance.

  3. Gender differences in associations between DSM-5 posttraumatic stress disorder symptom clusters and functional impairment in war veterans.

    Science.gov (United States)

    Meyer, Eric C; Konecky, Brian; Kimbrel, Nathan A; DeBeer, Bryann B; Marx, Brian P; Schumm, Jeremiah; Penk, Walter E; Gulliver, Suzy Bird; Morissette, Sandra B

    2018-05-01

    Understanding the links between posttraumatic stress disorder (PTSD) symptoms and functional impairment is essential for assisting veterans in transitioning to civilian life. Moreover, there may be differences between men and women in the relationships between PTSD symptoms and functional impairment. However, no prior studies have examined the links between functional impairment and the revised symptom clusters as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5; American Psychiatric Association, 2013) or whether the associations between PTSD symptom clusters and functional impairment differ by gender. We examined the associations between the DSM-5 PTSD symptom clusters and functional impairment in 252 trauma-exposed Iraq and Afghanistan war veterans (79 females). Regression analyses included demographic factors and exposure to both combat and military sexual trauma as covariates. In the total sample, both the intrusions cluster (β = .18, p = .045) and the negative alterations in cognition and mood cluster (β = .45, p < .001) were associated with global functional impairment. Among male veterans, global functional impairment was associated only with negative alterations in cognition and mood (β = .52, p < .001). However, by contrast, among female veterans, only marked alterations in arousal and reactivity were associated with global functional impairment (β = .35, p = .027). These findings suggest that there may be important gender differences with respect to the relationship between PTSD symptoms and functional impairment. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  4. Impact of ultraviolet-B radiation on planktonic fish larvae: Alteration of the osmoregulatory function

    Energy Technology Data Exchange (ETDEWEB)

    Sucre, Elliott, E-mail: elliott.sucre@univ-montp2.fr [AEO Team (Adaptation Ecophysiologique et Ontogenese), UMR 5119 Ecosym UM2, CNRS, IRD, Ifremer, UM1, Universite Montpellier 2, cc092, Pl. Eugene Bataillon, 34095 Montpellier, Cx 05 (France); Vidussi, Francesca [RESEAUX Team (Reseaux Planctoniques et Changement Environnemental), UMR 5119 Ecosym UM2, CNRS, IRD, Ifremer, UM1, Universite Montpellier 2, cc093, Pl. Eugene Bataillon, 34095 Montpellier, Cx 05 (France); Mostajir, Behzad [RESEAUX Team (Reseaux Planctoniques et Changement Environnemental), UMR 5119 Ecosym UM2, CNRS, IRD, Ifremer, UM1, Universite Montpellier 2, cc093, Pl. Eugene Bataillon, 34095 Montpellier, Cx 05 (France); Centre d' ecologie marine experimentale MEDIMEER (Mediterranean centre for Marine Ecosystem Experimental Research), Universite Montpellier 2-CNRS (UMS 3301), Station Mediterraneenne de l' Environnement Littoral, MEDIMEER, 2 Rue des Chantiers, 34200 Sete (France); Charmantier, Guy; Lorin-Nebel, Catherine [AEO Team (Adaptation Ecophysiologique et Ontogenese), UMR 5119 Ecosym UM2, CNRS, IRD, Ifremer, UM1, Universite Montpellier 2, cc092, Pl. Eugene Bataillon, 34095 Montpellier, Cx 05 (France)

    2012-03-15

    Coastal marine ecosystems are submitted to variations of several abiotic and biotic parameters, some of them related to global change. Among them the ultraviolet-B (UV-B) radiation (UVBR: 280-320 nm) may strongly impact planktonic fish larvae. The consequences of an increase of UVBR on the osmoregulatory function of Dicentrarchus labrax larvae have been investigated in this study. In young larvae of D. labrax, as in other teleosts, osmoregulation depends on tegumentary ion transporting cells, or ionocytes, mainly located on the skin of the trunk and of the yolk sac. As early D. labrax larvae passively drift in the top water column, ionocytes are exposed to solar radiation. The effect of UVBR on larval osmoregulation in seawater was evaluated through nanoosmometric measurements of the blood osmolality after exposure to different UV-B treatments. A loss of osmoregulatory capability occured in larvae after 2 days of low (50 {mu}W cm{sup -2}: 4 h L/20 h D) and medium (80 {mu}W cm{sup -2}: 4 h L/20 h D) UVBR exposure. Compared to control larvae kept in the darkness, a significant increase in blood osmolality, abnormal behavior and high mortalities were detected in larvae exposed to UVBR from 2 days on. At the cellular level, an important decrease in abundance of tegumentary ionocytes and mucous cells was observed after 2 days of exposure to UVBR. In the ionocytes, two major osmoeffectors were immunolocalized, the Na{sup +}/K{sup +}-ATPase and the Na{sup +}/K{sup +}/2Cl{sup -} cotransporter. Compared to controls, the fluorescent immunostaining was lower in UVBR-exposed larvae. We hypothesize that the impaired osmoregulation in UVBR-exposed larvae originates from the lower number of tegumentary ionocytes and mucous cells. This alteration of the osmoregulatory function could negatively impact the survival of young larvae at the surface water exposed to UVBR.

  5. Prevention of shockwave induced functional and morphological alterations: an overview.

    Science.gov (United States)

    Sarica, Kemal; Yencilek, Faruk

    2008-03-01

    Experimental as well as clinical findings reported in the literature suggest that treatment with shock wave lithotripsy (SWL) causes renal parenchymal damage mainly by generating free radicals through ischaemia/reperfusion injury mechanism. Although SWL-induced renal damage is well tolerated in the majority of healthy cases with no permanent functional and/or morphologic side effects, a subset of patients with certain risk factors requires close attention on this aspect among which the ones with pre-existing renal disorders, urinary tract infection, previous lithotripsy history and solitary kidneys could be mentioned. It is clear that in such patients lowering the number of shock waves (per session) could be beneficial and has been applied by the physicians as the first practical step of diminishing SWL induced parenchymal damage. On the other hand, taking the injurious effects of high energy shock wave (HESW) induced free radical formation on renal parenchyma and subsequent histopathologic alterations into account, physicians searched for some protective agents in an attempt to prevent or at least to limit the extent of the functional as well as the morphologic alterations. Among these agents calcium channel blocking agents (verapamil and nifedipine), antioxidant agents (allopurinol, vitamin E and selenium) and potassium citrate have been used to minimize these adverse effects. Additionally, therapeutic application of these agents on reducing stone recurrence particularly after SWL will gain more importance in the future in order to limit new stone formation in these cases. Lastly, as experimental and clinical studies have demonstrated, combination of anti-oxidants with free radical scavengers may provide superior renal protection against shock wave induced trauma. However, we believe that further investigations are certainly needed to determine the dose-response relationship between the damaging effects of SWL application and the protective role of these agents.

  6. Invasive carnivores alter ecological function and enhance complementarity in scavenger assemblages on ocean beaches.

    Science.gov (United States)

    Brown, Marion B; Schlacher, Thomas A; Schoeman, David S; Weston, Michael A; Huijbers, Chantal M; Olds, Andrew D; Connolly, Rod M

    2015-10-01

    Species composition is expected to alter ecological function in assemblages if species traits differ strongly. Such effects are often large and persistent for nonnative carnivores invading islands. Alternatively, high similarity in traits within assemblages creates a degree of functional redundancy in ecosystems. Here we tested whether species turnover results in functional ecological equivalence or complementarity, and whether invasive carnivores on islands significantly alter such ecological function. The model system consisted of vertebrate scavengers (dominated by raptors) foraging on animal carcasses on ocean beaches on two Australian islands, one with and one without invasive red foxes (Vulpes vulpes). Partitioning of scavenging events among species, carcass removal rates, and detection speeds were quantified using camera traps baited with fish carcasses at the dune-beach interface. Complete segregation of temporal foraging niches between mammals (nocturnal) and birds (diurnal) reflects complementarity in carrion utilization. Conversely, functional redundancy exists within the bird guild where several species of raptors dominate carrion removal in a broadly similar way. As predicted, effects of red foxes were large. They substantially changed the nature and rate of the scavenging process in the system: (1) foxes consumed over half (55%) of all carrion available at night, compared with negligible mammalian foraging at night on the fox-free island, and (2) significant shifts in the composition of the scavenger assemblages consuming beach-cast carrion are the consequence of fox invasion at one island. Arguably, in the absence of other mammalian apex predators, the addition of red foxes creates a new dimension of functional complementarity in beach food webs. However, this functional complementarity added by foxes is neither benign nor neutral, as marine carrion subsidies to coastal red fox populations are likely to facilitate their persistence as exotic

  7. Land use intensification alters ecosystem multifunctionality via loss of biodiversity and changes to functional composition

    OpenAIRE

    Allan, Eric; Manning, Pete; et al

    2015-01-01

    Global change, especially land-use intensification, affects human well-being by impacting the deliv-ery of multiple ecosystem services (multifunctionality). However, whether biodiversity loss is amajor component of global change effects on multifunctionality in real-world ecosystems, as inexperimental ones, remains unclear. Therefore, we assessed biodiversity, functional compositionand 14 ecosystem services on 150 agricultural grasslands differing in land-use intensity. We alsointroduce five mu...

  8. Land use intensification alters ecosystem multifunctionality via loss of biodiversity and changes to functional composition.

    OpenAIRE

    Allan Eric; Manning Pete; Alt Fabian; Binkenstein Julia; Blaser Stefan; Blüthgen Nico; Böhm Stefan; Grassein Fabrice; Hölzel Norbert; Klaus Valentin H.; Kleinebecker Till; Morrys Elisabeth Kathryn; Oelmann Yvonne; Prati Daniel; Renner Sven C.

    2015-01-01

    Abstract Global change, especially land?use intensification, affects human well?being by impacting the delivery of multiple ecosystem services (multifunctionality). However, whether biodiversity loss is a major component of global change effects on multifunctionality in real?world ecosystems, as in experimental ones, remains unclear. Therefore, we assessed biodiversity, functional composition and 14 ecosystem services on 150 agricultural grasslands differing in land?use intensity. We also int...

  9. Scanning the Global Environment. A framework and methodology for UNEP's reporting functions

    OpenAIRE

    Swart RJ; Bakkes JA; Niessen LW; Rotmans J; Vries HJM de; Weterings R; Rijksinstituut voor Volksgezondheid en Milieuhygiene RIVM; United Nations Environment Programme UNEP; MTV; ISC; VTV; CWM; SB4; TNO Centre for Technology and Policy Studies

    1994-01-01

    A conceptual framework for UNEP's reporting functions is proposed, aimed at supporting strategic environmental policy development. To this end information should be provided about the past, current and future state of the environment as a function of demographic and socio-economic developments. The policy relevance of the existing global environmental reporting functions may be improved considerably by introducing three new elements: (1) the application of integrated conceptual frameworks and...

  10. Diesel exhaust particle exposure in vitro alters monocyte differentiation and function.

    Directory of Open Access Journals (Sweden)

    Nazia Chaudhuri

    Full Text Available Air pollution by diesel exhaust particles is associated with elevated mortality and increased hospital admissions in individuals with respiratory diseases such as asthma and chronic obstructive pulmonary disease. During active inflammation monocytes are recruited to the airways and can replace resident alveolar macrophages. We therefore investigated whether chronic fourteen day exposure to low concentrations of diesel exhaust particles can alter the phenotype and function of monocytes from healthy individuals and those with chronic obstructive pulmonary disease. Monocytes were purified from the blood of healthy individuals and people with a diagnosis of chronic obstructive pulmonary disease. Monocyte-derived macrophages were generated in the presence or absence of diesel exhaust particles and their phenotypes studied through investigation of their lifespan, cytokine generation in response to Toll like receptor agonists and heat killed bacteria, and expression of surface markers. Chronic fourteen day exposure of monocyte-derived macrophages to concentrations of diesel exhaust particles >10 µg/ml caused mitochondrial and lysosomal dysfunction, and a gradual loss of cells over time both in healthy and chronic obstructive pulmonary disease individuals. Chronic exposure to lower concentrations of diesel exhaust particles impaired CXCL8 cytokine responses to lipopolysaccharide and heat killed E. coli, and this phenotype was associated with a reduction in CD14 and CD11b expression. Chronic diesel exhaust particle exposure may therefore alter both numbers and function of lung macrophages differentiating from locally recruited monocytes in the lungs of healthy people and patients with chronic obstructive pulmonary disease.

  11. Global terrestrial biogeochemistry: Perturbations, interactions, and time scales

    Energy Technology Data Exchange (ETDEWEB)

    Braswell, B.H. Jr.

    1996-12-01

    Global biogeochemical processes are being perturbed by human activity, principally that which is associated with industrial activity and expansion of urban and agricultural complexes. Perturbations have manifested themselves at least since the beginning of the 19th Century, and include emissions of CO{sub 2} and other pollutants from fossil fuel combustion, agricultural emissions of reactive nitrogen, and direct disruption of ecosystem function through land conversion. These perturbations yield local impacts, but there are also global consequences that are the sum of local-scale influences. Several approaches to understanding the global-scale implications of chemical perturbations to the Earth system are discussed. The lifetime of anthropogenic CO{sub 2} in the atmosphere is an important concept for understanding the current and future commitment to an altered atmospheric heat budget. The importance of the terrestrial biogeochemistry relative to the lifetime of excess CO{sub 2} is demonstrated using dynamic, aggregated models of the global carbon cycle.

  12. Analysis of Altered Baseline Brain Activity in Drug-Naive Adult Patients with Social Anxiety Disorder Using Resting-State Functional MRI

    OpenAIRE

    Qiu, Changjian; Feng, Yuan; Meng, Yajing; Liao, Wei; Huang, Xiaoqi; Lui, Su; Zhu, Chunyan; Chen, Huafu; Gong, Qiyong; Zhang, Wei

    2015-01-01

    Objective We hypothesize that the amplitude of low-frequency fluctuations (ALFF) is involved in the altered regional baseline brain function in social anxiety disorder (SAD). The aim of the study was to analyze the altered baseline brain activity in drug-naive adult patients with SAD. Methods We investigated spontaneous and baseline brain activities by obtaining the resting-state functional magnetic resonance imaging data of 20 drug-na?ve adult SAD patients and 19 healthy controls. Voxels wer...

  13. Co-altered functional networks and brain structure in unmedicated patients with bipolar and major depressive disorders.

    Science.gov (United States)

    He, Hao; Sui, Jing; Du, Yuhui; Yu, Qingbao; Lin, Dongdong; Drevets, Wayne C; Savitz, Jonathan B; Yang, Jian; Victor, Teresa A; Calhoun, Vince D

    2017-12-01

    Bipolar disorder (BD) and major depressive disorder (MDD) share similar clinical characteristics that often obscure the diagnostic distinctions between their depressive conditions. Both functional and structural brain abnormalities have been reported in these two disorders. However, the direct link between altered functioning and structure in these two diseases is unknown. To elucidate this relationship, we conducted a multimodal fusion analysis on the functional network connectivity (FNC) and gray matter density from MRI data from 13 BD, 40 MDD, and 33 matched healthy controls (HC). A data-driven fusion method called mCCA+jICA was used to identify the co-altered FNC and gray matter components. Comparing to HC, BD exhibited reduced gray matter density in the parietal and occipital cortices, which correlated with attenuated functional connectivity within sensory and motor networks, as well as hyper-connectivity in regions that are putatively engaged in cognitive control. In addition, lower gray matter density was found in MDD in the amygdala and cerebellum. High accuracy in discriminating across groups was also achieved by trained classification models, implying that features extracted from the fusion analysis hold the potential to ultimately serve as diagnostic biomarkers for mood disorders.

  14. Global biogeographical pattern of ecosystem functional types derived from earth observation data

    DEFF Research Database (Denmark)

    Ivits, Eva; Cherlet, Michael; Horion, Stéphanie Marie Anne F

    2013-01-01

    correspondence of the EFTs to global climate and also to land use classification. The results show the great potential of Earth Observation derived parameters for the quantification of ecosystem functional dynamics and for providing reference status information for future assessments of ecosystem changes........ The association of the EFTs with existing climate and land cover classifications was demonstrated via Detrended Correspondence Analysis (DCA). The ordination indicated good description of the global environmental gradient by the EFTs, supporting the understanding of phenological and productivity dynamics...... of global ecosystems. Climatic constraints of vegetation growth explained 50% of variation in the phenological data along the EFTs showing that part of the variation in the global phenological gradient is not climate related but is unique to the Earth Observation derived variables. DCA demonstrated good...

  15. The neurobiology of oppositional defiant disorder and conduct disorder: altered functioning in three mental domains.

    Science.gov (United States)

    Matthys, Walter; Vanderschuren, Louk J M J; Schutter, Dennis J L G

    2013-02-01

    This review discusses neurobiological studies of oppositional defiant disorder and conduct disorder within the conceptual framework of three interrelated mental domains: punishment processing, reward processing, and cognitive control. First, impaired fear conditioning, reduced cortisol reactivity to stress, amygdala hyporeactivity to negative stimuli, and altered serotonin and noradrenaline neurotransmission suggest low punishment sensitivity, which may compromise the ability of children and adolescents to make associations between inappropriate behaviors and forthcoming punishments. Second, sympathetic nervous system hyporeactivity to incentives, low basal heart rate associated with sensation seeking, orbitofrontal cortex hyporeactiviy to reward, and altered dopamine functioning suggest a hyposensitivity to reward. The associated unpleasant emotional state may make children and adolescents prone to sensation-seeking behavior such as rule breaking, delinquency, and substance abuse. Third, impairments in executive functions, especially when motivational factors are involved, as well as structural deficits and impaired functioning of the paralimbic system encompassing the orbitofrontal and cingulate cortex, suggest impaired cognitive control over emotional behavior. In the discussion we argue that more insight into the neurobiology of oppositional defiance disorder and conduct disorder may be obtained by studying these disorders separately and by paying attention to the heterogeneity of symptoms within each disorder.

  16. A prospective study of grey matter and cognitive function alterations in chemotherapy-treated breast cancer patients.

    Science.gov (United States)

    Lepage, Chris; Smith, Andra M; Moreau, Jeremy; Barlow-Krelina, Emily; Wallis, Nancy; Collins, Barbara; MacKenzie, Joyce; Scherling, Carole

    2014-01-01

    Subsequent to chemotherapy treatment, breast cancer patients often report a decline in cognitive functioning that can adversely impact many aspects of their lives. Evidence has mounted in recent years indicating that a portion of breast cancer survivors who have undergone chemotherapy display reduced performance on objective measures of cognitive functioning relative to comparison groups. Neurophysiological support for chemotherapy-related cognitive impairment has been accumulating due to an increase in neuroimaging studies in this field; however, longitudinal studies are limited and have not examined the relationship between structural grey matter alterations and neuropsychological performance. The aim of this study was to extend the cancer-cognition literature by investigating the association between grey matter attenuation and objectively measured cognitive functioning in chemotherapy-treated breast cancer patients. Female breast cancer patients (n = 19) underwent magnetic resonance imaging after surgery but before commencing chemotherapy, one month following treatment, and one year after treatment completion. Individually matched controls (n = 19) underwent imaging at similar intervals. All participants underwent a comprehensive neuropsychological battery comprising four cognitive domains at these same time points. Longitudinal grey matter changes were investigated using voxel-based morphometry. One month following chemotherapy, patients had distributed grey matter volume reductions. One year after treatment, a partial recovery was observed with alterations persisting predominantly in frontal and temporal regions. This course was not observed in the healthy comparison group. Processing speed followed a similar trajectory within the patient group, with poorest scores obtained one month following treatment and some improvement evident one year post-treatment. This study provides further credence to patient claims of altered cognitive functioning

  17. Networks of global bird invasion altered by regional trade ban.

    Science.gov (United States)

    Reino, Luís; Figueira, Rui; Beja, Pedro; Araújo, Miguel B; Capinha, César; Strubbe, Diederik

    2017-11-01

    Wildlife trade is a major pathway for introduction of invasive species worldwide. However, how exactly wildlife trade influences invasion risk, beyond the transportation of individuals to novel areas, remains unknown. We analyze the global trade network of wild-caught birds from 1995 to 2011 as reported by CITES (Convention on International Trade in Endangered Species of Wild Fauna and Flora). We found that before the European Union ban on imports of wild-caught birds, declared in 2005, invasion risk was closely associated with numbers of imported birds, diversity of import sources, and degree of network centrality of importer countries. After the ban, fluxes of global bird trade declined sharply. However, new trade routes emerged, primarily toward the Nearctic, Afrotropical, and Indo-Malay regions. Although regional bans can curtail invasion risk globally, to be fully effective and prevent rerouting of trade flows, bans should be global.

  18. Global study of nuclear modifications on parton distribution functions

    Directory of Open Access Journals (Sweden)

    Rong Wang

    2017-07-01

    Full Text Available A global analysis of nuclear medium modifications of parton distributions is presented using deeply inelastic scattering data of various nuclear targets. Two obtained data sets are provided for quark and gluon nuclear modification factors, referred as nIMParton16. One is from the global fit only to the experimental data of isospin-scalar nuclei (Set A, and the other is from the fit to all the measured nuclear data (Set B. The scale-dependence is described by DGLAP equations with nonlinear corrections in this work. The Fermi motion and off-shell effect, nucleon swelling, and parton–parton recombination are taken into account together for modeling the complicated x-dependence of nuclear modification. The nuclear gluon shadowing in this paper is dynamically generated by the QCD evolution of parton splitting and recombination processes with zero gluon density at the input scale. Sophisticated nuclear dependence of nuclear medium effects is studied with only two free parameters. With the obtained free parameters from the global analysis, the nuclear modifications of parton distribution functions of unmeasured nuclei can be predicted in our model. Nuclear modification of deuteron is also predicted and shown with recent measurement at JLab.

  19. Fragmentation: Loss of global coherence or breakdown of modularity in functional brain architecture?

    Directory of Open Access Journals (Sweden)

    Daan evan den Berg

    2012-03-01

    Full Text Available Psychiatric illnesses characterised by disorganized cognition, such as schizophrenia, have been described in terms of fragmentation and hence understood as reduction in functional brain connectivity, particularly in prefrontal and parietal areas. However, as graph-theory shows, relatively small numbers of nonlocal connections are sufficient to ensure global coherence in the modular small world network structure of the brain. We reconsider fragmentation in this perspective. Computational studies have shown that for a given level of connectivity in a model of coupled nonlinear oscillators, modular small-world networks evolve from an initially random organization. Here we demonstrate that with decreasing connectivity, the probability of evolving into a modular small-world network breaks down at a critical point, which scales to the percolation function of random networks with a universal exponent of α=1.17. Thus, according to the model, local modularity systematically breaks down before there is loss of global coherence in network connectivity. We therefore propose that fragmentation may involve, at least in its initial stages, the inability of a dynamically evolving network to sustain a modular small-world structure. The result is in a shift in the balance in schizophrenia from local to global functional connectivity.

  20. Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity

    Directory of Open Access Journals (Sweden)

    Mette J. Jacobsen

    2016-01-01

    Full Text Available Obesity is associated with immunological perturbations that contribute to insulin resistance. Epigenetic mechanisms can control immune functions and have been linked to metabolic complications, although their contribution to insulin resistance still remains unclear. In this study, we investigated the link between metabolic dysfunction and immune alterations with the epigenetic signature in leukocytes in a porcine model of obesity. Global DNA methylation of circulating leukocytes, adipose tissue leukocyte trafficking, and macrophage polarisation were established by flow cytometry. Adipose tissue inflammation and metabolic function were further characterised by quantification of metabolites and expression levels of genes associated with obesity and inflammation. Here we show that obese pigs showed bigger visceral fat pads, higher levels of circulating LDL cholesterol, and impaired glucose tolerance. These changes coincided with impaired metabolism, sustained macrophages infiltration, and increased inflammation in the adipose tissue. Those immune alterations were linked to global DNA hypermethylation in both B-cells and T-cells. Our results provide novel insight into the possible contribution of immune cell epigenetics into the immunological disturbances observed in obesity. The dramatic changes in the transcriptomic and epigenetic signature of circulating lymphocytes reinforce the concept that epigenetic processes participate in the increased immune cell activation and impaired metabolic functions in obesity.

  1. Sensory phenomena related to tics, obsessive-compulsive symptoms, and global functioning in Tourette syndrome.

    Science.gov (United States)

    Kano, Yukiko; Matsuda, Natsumi; Nonaka, Maiko; Fujio, Miyuki; Kuwabara, Hitoshi; Kono, Toshiaki

    2015-10-01

    Sensory phenomena, including premonitory urges, are experienced by patients with Tourette syndrome (TS) and obsessive-compulsive disorder (OCD). The goal of the present study was to investigate such phenomena related to tics, obsessive-compulsive symptoms (OCS), and global functioning in Japanese patients with TS. Forty-one patients with TS were assessed using the University of São Paulo Sensory Phenomena Scale (USP-SPS), the Premonitory Urge for Tics Scale (PUTS), the Yale Global Tic Severity Scale (YGTSS), the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS), and the Global Assessment of Functioning (GAF) Scale. USP-SPS and PUTS total scores were significantly correlated with YGTSS total and vocal tics scores. Additionally, both sensory phenomena severity scores were significantly correlated with DY-BOCS total OCS scores. Of the six dimensional OCS scores, the USP-SPS scores were significantly correlated with measures of aggression and sexual/religious dimensions. Finally, the PUTS total scores were significantly and negatively correlated with GAF scores. By assessing premonitory urges and broader sensory phenomena, and by viewing OCS from a dimensional approach, this study provides significant insight into sensory phenomena related to tics, OCS, and global functioning in patients with TS. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Anti-correlated networks, global signal regression, and the effects of caffeine in resting-state functional MRI.

    Science.gov (United States)

    Wong, Chi Wah; Olafsson, Valur; Tal, Omer; Liu, Thomas T

    2012-10-15

    Resting-state functional connectivity magnetic resonance imaging is proving to be an essential tool for the characterization of functional networks in the brain. Two of the major networks that have been identified are the default mode network (DMN) and the task positive network (TPN). Although prior work indicates that these two networks are anti-correlated, the findings are controversial because the anti-correlations are often found only after the application of a pre-processing step, known as global signal regression, that can produce artifactual anti-correlations. In this paper, we show that, for subjects studied in an eyes-closed rest state, caffeine can significantly enhance the detection of anti-correlations between the DMN and TPN without the need for global signal regression. In line with these findings, we find that caffeine also leads to widespread decreases in connectivity and global signal amplitude. Using a recently introduced geometric model of global signal effects, we demonstrate that these decreases are consistent with the removal of an additive global signal confound. In contrast to the effects observed in the eyes-closed rest state, caffeine did not lead to significant changes in global functional connectivity in the eyes-open rest state. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Clinical symptoms predict concurrent social and global functioning in an early psychosis sample.

    Science.gov (United States)

    Cacciotti-Saija, Cristina; Langdon, Robyn; Ward, Philip B; Hickie, Ian B; Guastella, Adam J

    2018-04-01

    Although well established in chronic schizophrenia, the key determinants of functioning remain unknown during the early phase of a psychotic disorder. The aim of this study was to comprehensively examine the social cognitive, basic neurocognitive and clinical predictors of concurrent social functioning and global functioning in an early psychosis sample. This study examined the relationship between social cognition, basic neurocognition and clinical symptoms with concurrent functioning in 51 early psychosis individuals. Assessments included a range of self-report, observational and clinician-rated measures of cognitive, symptom severity and functioning domains. Results revealed a significant association between self-reported social function and lower levels of both social interaction anxiety and negative psychotic symptoms. A significant association was also observed between lower levels of negative psychotic symptoms and observed social functioning. Lastly, results demonstrated a significant association between reduced negative psychotic symptoms and clinician-rated global functioning. Clinical domains such as negative symptoms and social interaction anxiety significantly contribute to an optimal model predicting outcome during the early phase of a psychotic disorder. These clinical features may also provide useful markers of an individual's capacity for social participation. Clinical implications include the need for early targeted intervention to address social anxiety and negative psychotic symptoms to facilitate optimum patient outcome. © 2015 Wiley Publishing Asia Pty Ltd.

  4. Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation.

    Science.gov (United States)

    Manzoni, Claudia; Mamais, Adamantios; Dihanich, Sybille; McGoldrick, Phillip; Devine, Michael J; Zerle, Julia; Kara, Eleanna; Taanman, Jan-Willem; Healy, Daniel G; Marti-Masso, Jose-Felix; Schapira, Anthony H; Plun-Favreau, Helene; Tooze, Sharon; Hardy, John; Bandopadhyay, Rina; Lewis, Patrick A

    2013-11-29

    LRRK2 is one of the most important genetic contributors to Parkinson's disease (PD). Point mutations in this gene cause an autosomal dominant form of PD, but to date no cellular phenotype has been consistently linked with mutations in each of the functional domains (ROC, COR and Kinase) of the protein product of this gene. In this study, primary fibroblasts from individuals carrying pathogenic mutations in the three central domains of LRRK2 were assessed for alterations in the autophagy/lysosomal pathway using a combination of biochemical and cellular approaches. Mutations in all three domains resulted in alterations in markers for autophagy/lysosomal function compared to wild type cells. These data highlight the autophagy and lysosomal pathways as read outs for pathogenic LRRK2 function and as a marker for disease, and provide insight into the mechanisms linking LRRK2 function and mutations. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Altered functional connectivity architecture of the brain in medication overuse headache using resting state fMRI.

    Science.gov (United States)

    Chen, Zhiye; Chen, Xiaoyan; Liu, Mengqi; Dong, Zhao; Ma, Lin; Yu, Shengyuan

    2017-12-01

    Functional connectivity density (FCD) could identify the abnormal intrinsic and spontaneous activity over the whole brain, and a seed-based resting-state functional connectivity (RSFC) could further reveal the altered functional network with the identified brain regions. This may be an effective assessment strategy for headache research. This study is to investigate the RSFC architecture changes of the brain in the patients with medication overuse headache (MOH) using FCD and RSFC methods. 3D structure images and resting-state functional MRI data were obtained from 37 MOH patients, 18 episodic migraine (EM) patients and 32 normal controls (NCs). FCD was calculated to detect the brain regions with abnormal functional activity over the whole brain, and the seed-based RSFC was performed to explore the functional network changes in MOH and EM. The decreased FCD located in right parahippocampal gyrus, and the increased FCD located in left inferior parietal gyrus and right supramarginal gyrus in MOH compared with NC, and in right caudate and left insula in MOH compared with EM. RSFC revealed that decreased functional connectivity of the brain regions with decreased FCD anchored in the right dorsal-lateral prefrontal cortex, right frontopolar cortex in MOH, and in left temporopolar cortex and bilateral visual cortices in EM compared with NC, and in frontal-temporal-parietal pattern in MOH compared with EM. These results provided evidence that MOH and EM suffered from altered intrinsic functional connectivity architecture, and the current study presented a new perspective for understanding the neuromechanism of MOH and EM pathogenesis.

  6. Existence of global solutions to reaction-diffusion systems via a Lyapunov functional

    Directory of Open Access Journals (Sweden)

    Said Kouachi

    2001-10-01

    Full Text Available The purpose of this paper is to construct polynomial functionals (according to solutions of the coupled reaction-diffusion equations which give $L^{p}$-bounds for solutions. When the reaction terms are sufficiently regular, using the well known regularizing effect, we deduce the existence of global solutions. These functionals are obtained independently of work done by Malham and Xin [11].

  7. Altered Functional Subnetwork During Emotional Face Processing: A Potential Intermediate Phenotype for Schizophrenia.

    Science.gov (United States)

    Cao, Hengyi; Bertolino, Alessandro; Walter, Henrik; Schneider, Michael; Schäfer, Axel; Taurisano, Paolo; Blasi, Giuseppe; Haddad, Leila; Grimm, Oliver; Otto, Kristina; Dixson, Luanna; Erk, Susanne; Mohnke, Sebastian; Heinz, Andreas; Romanczuk-Seiferth, Nina; Mühleisen, Thomas W; Mattheisen, Manuel; Witt, Stephanie H; Cichon, Sven; Noethen, Markus; Rietschel, Marcella; Tost, Heike; Meyer-Lindenberg, Andreas

    2016-06-01

    Although deficits in emotional processing are prominent in schizophrenia, it has been difficult to identify neural mechanisms related to the genetic risk for this highly heritable illness. Prior studies have not found consistent regional activation or connectivity alterations in first-degree relatives compared with healthy controls, suggesting that a more comprehensive search for connectomic biomarkers is warranted. To identify a potential systems-level intermediate phenotype linked to emotion processing in schizophrenia and to examine the psychological association, task specificity, test-retest reliability, and clinical validity of the identified phenotype. The study was performed in university research hospitals from June 1, 2008, through December 31, 2013. We examined 58 unaffected first-degree relatives of patients with schizophrenia and 94 healthy controls with an emotional face-matching functional magnetic resonance imaging paradigm. Test-retest reliability was analyzed with an independent sample of 26 healthy participants. A clinical association study was performed in 31 patients with schizophrenia and 45 healthy controls. Data analysis was performed from January 1 to September 30, 2014. Conventional amygdala activity and seeded connectivity measures, graph-based global and local network connectivity measures, Spearman rank correlation, intraclass correlation, and gray matter volumes. Among the 152 volunteers included in the relative-control sample, 58 were unaffected first-degree relatives of patients with schizophrenia (mean [SD] age, 33.29 [12.56]; 38 were women), and 94 were healthy controls without a first-degree relative with mental illness (mean [SD] age, 32.69 [10.09] years; 55 were women). A graph-theoretical connectivity approach identified significantly decreased connectivity in a subnetwork that primarily included the limbic cortex, visual cortex, and subcortex during emotional face processing (cluster-level P corrected for familywise error =

  8. Altered emotion regulation capacity in social phobia as a function of comorbidity.

    Science.gov (United States)

    Burklund, Lisa J; Craske, Michelle G; Taylor, Shelley E; Lieberman, Matthew D

    2015-02-01

    Social phobia (SP) has been associated with amygdala hyperreactivity to fear-relevant stimuli. However, little is known about the neural basis of SP individuals' capacity to downregulate their responses to such stimuli and how such regulation varies as a function of comorbid depression and anxiety. We completed an functional magnetic resonance imaging (fMRI) study wherein SP participants without comorbidity (n = 30), with comorbid depression (n = 18) and with comorbid anxiety (n = 19) and healthy controls (n = 15) were scanned while completing an affect labeling emotion regulation task. Individuals with SP as a whole exhibited a reversal of the pattern observed in healthy controls in that they showed upregulation of amygdala activity during affect labeling. However, subsequent analyses revealed a more complex picture based on comorbidity type. Although none of the SP subgroups showed the normative pattern of amygdala downregulation, it was those with comorbid depression specifically who showed significant upregulation. Effects could not be attributed to differences in task performance, amygdala reactivity or right ventral lateral prefrontal cortex (RVLPFC) engagement, but may stem from dysfunctional communication between amygdala and RVLPFC. Furthermore, the particularly altered emotion regulation seen in those with comorbid depression could not be fully explained by symptom severity or state anxiety. Results reveal altered emotion regulation in SP, especially when comorbid with depression. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. Intake of phthalate-tainted foods alters thyroid functions in Taiwanese children.

    Directory of Open Access Journals (Sweden)

    Ming-Tsang Wu

    Full Text Available BACKGROUND: On April-May, 2011, two Taiwan chemical companies were found to have intentionally added phthalates, Di-(2-ethylhexyl phthalate (DEHP and/or Di-isononyl phthalate, as a substitute of emulsifier to many foodstuffs. This study aimed to investigate whether exposure to these foods altered endocrine functions in children aged ≤10 years and, if so, whether those changes could be reversed by stopping exposure. METHODS: One Phthalates Clinic for Children was established in southern Taiwan between May 31 and June 17, 2011. All eligible children had their exposure information, blood and/or urine specimens collected. Endocrine functions were assessed in serum. The exposure groups were categorized into three (High, >500 ppm, Low, 1-500 ppm, and No, <1 ppm of DEHP. After six months, some children were followed up for the selected endocrine hormones. RESULTS: Sixty children were eligible in this study; all were Tanner stage 1 with no pubic hair. Compared to non-exposed group, both high and low exposure groups had significantly lower serum thyroid-stimulating hormone (TSH levels (P = 0.001 and 0.024. At six months follow-up, serum triiodothyronine (T3 levels was significantly changed (P = 0.034 in high exposure group (n = 13. For serum estradiol (E2, the detectable rate (≥8 pg/mL decreased from 76.9% (10/13 to 30.8% (4/13 (P = 0.070. CONCLUSIONS: This study shows that serum TSH levels can be altered when children were exposed to high concentrations of phthalate-tainted foodstuffs. Serum E2 and T3 may be partially recovered after stopping exposure.

  10. Association between functional alterations of senescence and senility and disorders of gait and balance.

    Science.gov (United States)

    Teixeira-Leite, Homero; Manhães, Alex C

    2012-07-01

    Declines in cognition and mobility are frequently observed in the elderly, and it has been suggested that the appearance of gait disorders in older individuals may constitute a marker of cognitive decline that precedes significant findings in functional performance screening tests. This study sought to evaluate the relationship between functional capacities and gait and balance in an elderly community monitored by the Preventive and Integrated Care Unit of the Hospital Adventista Silvestre in Rio de Janeiro, RJ, Brazil. Elderly individuals (193 females and 90 males) were submitted to a broad geriatric evaluation, which included the following tests: 1) a performance-oriented mobility assessment (POMA) to evaluate gait; 2) a mini-mental state examination (MMSE); 3) the use of Katz and Lawton scales to assess functional capacity; 4) the application of the geriatric depression scale (GDS); and 5) a mini-nutritional assessment (MNA) scale. Reductions in MMSE, Katz and Lawton scores were associated with reductions in POMA scores, and we also observed that significant reductions in POMA scores were present in persons for whom the MMSE and Katz scores did not clearly indicate cognitive dysfunction. We also demonstrated that a decline in the scores obtained with the GDS and MNA scales was associated with a decline in the POMA scores. Considering that significant alterations in the POMA scores were observed prior to the identification of significant alterations in cognitive capacity using either the MMSE or the Katz systems, a prospective study seems warranted to assess the predictive capacity of POMA scores regarding the associated decline in functional capacity.

  11. Global brands: a brief review

    OpenAIRE

    Martín Hernani-Merino; Rossana Montero–Santos

    2015-01-01

    Markets globalization has placed global brands as central players in the economic, cultural and psychological fields; the evidence is everywhere (Özsomer, Batra, Chattopadhyay & Hofstede, 2012). Therefore, many multinational companies are altering their brand portfolios in favor of global brands (Özsomer et al, 2012;. Steenkamp, Batra & Alden, 2003). Thus, this essay aims to analyze the concepts and research related to the construct of global brands. The paper seeks to understand the ...

  12. Lyapunov functions and global stability for SIR and SEIR models with age-dependent susceptibility

    KAUST Repository

    Korobeinikov, Andrei; Melnik, Andrey V.

    2013-01-01

    We consider global asymptotic properties for the SIR and SEIR age structured models for infectious diseases where the susceptibility depends on the age. Using the direct Lyapunov method with Volterra type Lyapunov functions, we establish conditions for the global stability of a unique endemic steady state and the infection-free steady state.

  13. Altered resting-state functional connectivity in patients with chronic bilateral vestibular failure.

    Science.gov (United States)

    Göttlich, Martin; Jandl, Nico M; Wojak, Jann F; Sprenger, Andreas; von der Gablentz, Janina; Münte, Thomas F; Krämer, Ulrike M; Helmchen, Christoph

    2014-01-01

    Patients with bilateral vestibular failure (BVF) suffer from gait unsteadiness, oscillopsia and impaired spatial orientation. Brain imaging studies applying caloric irrigation to patients with BVF have shown altered neural activity of cortical visual-vestibular interaction: decreased bilateral neural activity in the posterior insula and parietal operculum and decreased deactivations in the visual cortex. It is unknown how this affects functional connectivity in the resting brain and how changes in connectivity are related to vestibular impairment. We applied a novel data driven approach based on graph theory to investigate altered whole-brain resting-state functional connectivity in BVF patients (n= 22) compared to age- and gender-matched healthy controls (n= 25) using resting-state fMRI. Changes in functional connectivity were related to subjective (vestibular scores) and objective functional parameters of vestibular impairment, specifically, the adaptive changes during active (self-guided) and passive (investigator driven) head impulse test (HIT) which reflects the integrity of the vestibulo-ocular reflex (VOR). BVF patients showed lower bilateral connectivity in the posterior insula and parietal operculum but higher connectivity in the posterior cerebellum compared to controls. Seed-based analysis revealed stronger connectivity from the right posterior insula to the precuneus, anterior insula, anterior cingulate cortex and the middle frontal gyrus. Excitingly, functional connectivity in the supramarginal gyrus (SMG) of the inferior parietal lobe and posterior cerebellum correlated with the increase of VOR gain during active as compared to passive HIT, i.e., the larger the adaptive VOR changes the larger was the increase in regional functional connectivity. Using whole brain resting-state connectivity analysis in BVF patients we show that enduring bilateral deficient or missing vestibular input leads to changes in resting-state connectivity of the brain. These

  14. Altered functional connectivity differs in stroke survivors with impaired touch sensation following left and right hemisphere lesions

    Directory of Open Access Journals (Sweden)

    Peter Goodin

    Full Text Available One in two survivors experience impairment in touch sensation after stroke. The nature of this impairment is likely associated with changes associated with the functional somatosensory network of the brain; however few studies have examined this. In particular, the impact of lesioned hemisphere has not been investigated. We examined resting state functional connectivity in 28 stroke survivors, 14 with left hemisphere and 14 with right hemisphere lesion, and 14 healthy controls. Contra-lesional hands showed significantly decreased touch discrimination. Whole brain functional connectivity (FC data was extracted from four seed regions, i.e. primary (S1 and secondary (S2 somatosensory cortices in both hemispheres. Whole brain FC maps and Laterality Indices (LI were calculated for subgroups. Inter-hemispheric FC was greater in healthy controls compared to the combined stroke cohort from the left S1 seed and bilateral S2 seeds. The left lesion subgroup showed decreased FC, relative to controls, from left ipsi-lesional S1 to contra-lesional S1 and to distributed temporal, occipital and parietal regions. In comparison, the right lesion group showed decreased connectivity from contra-lesional left S1 and bilateral S2 to ipsi-lesional parietal operculum (S2, and to occipital and temporal regions. The right lesion group also showed increased intra-hemispheric FC from ipsi-lesional right S1 to inferior parietal regions compared to controls. In comparison to the left lesion group, those with right lesion showed greater intra-hemispheric connectivity from left S1 to left parietal and occipital regions and from right S1 to right angular and parietal regions. Laterality Indices were significantly greater for stroke subgroups relative to matched controls for contra-lesional S1 (left lesion group and contra-lesional S2 (both groups. We provide evidence of altered functional connectivity within the somatosensory network, across both hemispheres, and to other

  15. In Utero Exposure to Arsenic Alters Lung Development and Genes Related to Immune and Mucociliary Function in Mice

    OpenAIRE

    Ramsey, Kathryn A.; Bosco, Anthony; McKenna, Katherine L.; Carter, Kim W.; Elliot, John G.; Berry, Luke J.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2012-01-01

    Background: Exposure to arsenic via drinking water is a global environmental health problem. In utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in early adulthood. Objectives: We aimed to investigate how arsenic exposure in early life alters lung development and pathways involved in innate immunity. Methods: Pregnant BALB/c, C57BL/6, and C3H/HeARC mice were exposed to 0 (control) or 100 ?g/L...

  16. Sex and disease-related alterations of anterior insula functional connectivity in chronic abdominal pain.

    Science.gov (United States)

    Hong, Jui-Yang; Kilpatrick, Lisa A; Labus, Jennifer S; Gupta, Arpana; Katibian, David; Ashe-McNalley, Cody; Stains, Jean; Heendeniya, Nuwanthi; Smith, Suzanne R; Tillisch, Kirsten; Naliboff, Bruce; Mayer, Emeran A

    2014-10-22

    Resting-state functional magnetic resonance imaging has been used to investigate intrinsic brain connectivity in healthy subjects and patients with chronic pain. Sex-related differences in the frequency power distribution within the human insula (INS), a brain region involved in the integration of interoceptive, affective, and cognitive influences, have been reported. Here we aimed to test sex and disease-related alterations in the intrinsic functional connectivity of the dorsal anterior INS. The anterior INS is engaged during goal-directed tasks and modulates the default mode and executive control networks. By comparing functional connectivity of the dorsal anterior INS in age-matched female and male healthy subjects and patients with irritable bowel syndrome (IBS), a common chronic abdominal pain condition, we show evidence for sex and disease-related alterations in the functional connectivity of this region: (1) male patients compared with female patients had increased positive connectivity of the dorsal anterior INS bilaterally with the medial prefrontal cortex (PFC) and dorsal posterior INS; (2) female patients compared with male patients had greater negative connectivity of the left dorsal anterior INS with the left precuneus; (3) disease-related differences in the connectivity between the bilateral dorsal anterior INS and the dorsal medial PFC were observed in female subjects; and (4) clinical characteristics were significantly correlated to the insular connectivity with the dorsal medial PFC in male IBS subjects and with the precuneus in female IBS subjects. These findings are consistent with the INS playing an important role in modulating the intrinsic functional connectivity of major networks in the resting brain and show that this role is influenced by sex and diagnosis. Copyright © 2014 the authors 0270-6474/14/3414252-08$15.00/0.

  17. The influence of stress on neuroinflammation and alterations in brain structure and function in major depressive disorder.

    Science.gov (United States)

    Kim, Yong-Ku; Won, Eunsoo

    2017-06-30

    Major depressive disorder (MDD) is a condition which has often been associated with chronic stress. The sympathetic nervous system is continuously activated without the normal counteraction of the parasympathetic nervous system under the influence of chronic stress. As a result, epinephrine and norepinephrine levels are increased, and acetylcholine levels are decreased, which in turn can increase the levels of pro-inflammatory cytokines. Peripheral inflammatory responses can access the brain, with neuroinflammation contributing to the increase in neurotoxic kynurenine pathway metabolites such as 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid, and decrease in neuroprotective metabolites such as kynurenic acid. Pro-inflammatory cytokines can also exert direct neurotoxic effects on specific brain regions. Previous imaging studies have reported associations between pro-inflammatory states and alterations in brain regions involved in emotional regulation, including the hippocampus, amygdala and anterior cingulate cortex. Alterations in structure and function of such brain areas due to the neurotoxic effects of increased inflammation may be associated with the pathophysiology of depression. This review focuses the influence of stress on neuroinflammation which may cause alterations in brain structure and function in MDD. Copyright © 2017. Published by Elsevier B.V.

  18. Altered functional connectivity in lesional peduncular hallucinosis with REM sleep behavior disorder.

    Science.gov (United States)

    Geddes, Maiya R; Tie, Yanmei; Gabrieli, John D E; McGinnis, Scott M; Golby, Alexandra J; Whitfield-Gabrieli, Susan

    2016-01-01

    Brainstem lesions causing peduncular hallucinosis (PH) produce vivid visual hallucinations occasionally accompanied by sleep disorders. Overlapping brainstem regions modulate visual pathways and REM sleep functions via gating of thalamocortical networks. A 66-year-old man with paroxysmal atrial fibrillation developed abrupt-onset complex visual hallucinations with preserved insight and violent dream enactment behavior. Brain MRI showed restricted diffusion in the left rostrodorsal pons suggestive of an acute ischemic stroke. REM sleep behavior disorder (RBD) was diagnosed on polysomnography. We investigated the integrity of ponto-geniculate-occipital circuits with seed-based resting-state functional connectivity MRI (rs-fcMRI) in this patient compared to 46 controls. Rs-fcMRI revealed significantly reduced functional connectivity between the lesion and lateral geniculate nuclei (LGN), and between LGN and visual association cortex compared to controls. Conversely, functional connectivity between brainstem and visual association cortex, and between visual association cortex and prefrontal cortex (PFC) was significantly increased in the patient. Focal damage to the rostrodorsal pons is sufficient to cause RBD and PH in humans, suggesting an overlapping mechanism in both syndromes. This lesion produced a pattern of altered functional connectivity consistent with disrupted visual cortex connectivity via de-afferentation of thalamocortical pathways. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  19. Long-term artificial sweetener acesulfame potassium treatment alters neurometabolic functions in C57BL/6J mice.

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    Full Text Available With the prevalence of obesity, artificial, non-nutritive sweeteners have been widely used as dietary supplements that provide sweet taste without excessive caloric load. In order to better understand the overall actions of artificial sweeteners, especially when they are chronically used, we investigated the peripheral and central nervous system effects of protracted exposure to a widely used artificial sweetener, acesulfame K (ACK. We found that extended ACK exposure (40 weeks in normal C57BL/6J mice demonstrated a moderate and limited influence on metabolic homeostasis, including altering fasting insulin and leptin levels, pancreatic islet size and lipid levels, without affecting insulin sensitivity and bodyweight. Interestingly, impaired cognitive memory functions (evaluated by Morris Water Maze and Novel Objective Preference tests were found in ACK-treated C57BL/6J mice, while no differences in motor function and anxiety levels were detected. The generation of an ACK-induced neurological phenotype was associated with metabolic dysregulation (glycolysis inhibition and functional ATP depletion and neurosynaptic abnormalities (dysregulation of TrkB-mediated BDNF and Akt/Erk-mediated cell growth/survival pathway in hippocampal neurons. Our data suggest that chronic use of ACK could affect cognitive functions, potentially via altering neuro-metabolic functions in male C57BL/6J mice.

  20. Whole-brain structural topology in adult attention-deficit/hyperactivity disorder: Preserved global – disturbed local network organization

    Directory of Open Access Journals (Sweden)

    Justina Sidlauskaite

    2015-01-01

    Full Text Available Prior studies demonstrate altered organization of functional brain networks in attention-deficit/hyperactivity disorder (ADHD. However, the structural underpinnings of these functional disturbances are poorly understood. In the current study, we applied a graph-theoretic approach to whole-brain diffusion magnetic resonance imaging data to investigate the organization of structural brain networks in adults with ADHD and unaffected controls using deterministic fiber tractography. Groups did not differ in terms of global network metrics — small-worldness, global efficiency and clustering coefficient. However, there were widespread ADHD-related effects at the nodal level in relation to local efficiency and clustering. The affected nodes included superior occipital, supramarginal, superior temporal, inferior parietal, angular and inferior frontal gyri, as well as putamen, thalamus and posterior cerebellum. Lower local efficiency of left superior temporal and supramarginal gyri was associated with higher ADHD symptom scores. Also greater local clustering of right putamen and lower local clustering of left supramarginal gyrus correlated with ADHD symptom severity. Overall, the findings indicate preserved global but altered local network organization in adult ADHD implicating regions underpinning putative ADHD-related neuropsychological deficits.

  1. Neuromorphological and wiring pattern alterations effects on brain function: a mixed experimental and computational approach.

    Directory of Open Access Journals (Sweden)

    Linus Manubens-Gil

    2015-04-01

    In addition, the study of fixed intact brains (by means of the state of the art CLARITY technique brings us closer to biologically and medically relevant situations, allowing not only to confirm whether the functional links in neuronal cultures are also present in vivo, but also enabling the introduction of functional information (like behavioral studies and functional imaging and another layer of structural alterations such as brain region morphology, neuronal density, and long-range connectivity. Taking together the experimental information from these systems we want to feed self-developed computational models that allow us to understand what are the fundamental characteristics of the observed connectivity patterns and the impact of each of the alterations on neuronal network function. These models will also provide a framework able to account for the emergent properties that bridge the gap between spontaneous electrical activity arousal/transmission and higher order information processing and memory storage capacities in the brain. As an additional part of the project we are now working on the application of the clearing, labeling and imaging protocols to human biopsy samples. Our aim is to obtain neuronal architecture and connectivity information from focal cortical dysplasia microcircuits using samples from intractable temporal lobe epilepsy patients that undergo deep-brain electrode recording diagnosis and posterior surgical extraction of the tissue. Our computational models can allow us to discern the contributions of the observed abnormalities to neuronal hyperactivity and epileptic seizure generation.

  2. How linear features alter predator movement and the functional response.

    KAUST Repository

    McKenzie, Hannah W

    2012-01-18

    In areas of oil and gas exploration, seismic lines have been reported to alter the movement patterns of wolves (Canis lupus). We developed a mechanistic first passage time model, based on an anisotropic elliptic partial differential equation, and used this to explore how wolf movement responses to seismic lines influence the encounter rate of the wolves with their prey. The model was parametrized using 5 min GPS location data. These data showed that wolves travelled faster on seismic lines and had a higher probability of staying on a seismic line once they were on it. We simulated wolf movement on a range of seismic line densities and drew implications for the rate of predator-prey interactions as described by the functional response. The functional response exhibited a more than linear increase with respect to prey density (type III) as well as interactions with seismic line density. Encounter rates were significantly higher in landscapes with high seismic line density and were most pronounced at low prey densities. This suggests that prey at low population densities are at higher risk in environments with a high seismic line density unless they learn to avoid them.

  3. How linear features alter predator movement and the functional response.

    KAUST Repository

    McKenzie, Hannah W; Merrill, Evelyn H; Spiteri, Raymond J; Lewis, Mark A

    2012-01-01

    In areas of oil and gas exploration, seismic lines have been reported to alter the movement patterns of wolves (Canis lupus). We developed a mechanistic first passage time model, based on an anisotropic elliptic partial differential equation, and used this to explore how wolf movement responses to seismic lines influence the encounter rate of the wolves with their prey. The model was parametrized using 5 min GPS location data. These data showed that wolves travelled faster on seismic lines and had a higher probability of staying on a seismic line once they were on it. We simulated wolf movement on a range of seismic line densities and drew implications for the rate of predator-prey interactions as described by the functional response. The functional response exhibited a more than linear increase with respect to prey density (type III) as well as interactions with seismic line density. Encounter rates were significantly higher in landscapes with high seismic line density and were most pronounced at low prey densities. This suggests that prey at low population densities are at higher risk in environments with a high seismic line density unless they learn to avoid them.

  4. Increased cortical thickness and altered functional connectivity of the right superior temporal gyrus in left-handers.

    Science.gov (United States)

    Li, Meiling; Chen, Heng; Wang, Junping; Liu, Feng; Wang, Yifeng; Lu, Fengmei; Yu, Chunshui; Chen, Huafu

    2015-01-01

    Altered structure in the temporal cortex has been implicated in the variable language laterality of left-handers (LH). The neuroanatomy of language lateralization and the corresponding synchronous functional connectivity (FC) in handedness cohorts are not, however, fully understood. We used structural and resting-state functional magnetic resonance imaging (fMRI) data to investigate the effect of altered cortical thickness on FC in LH and right-handers (RH). Whole-brain cortical thickness was calculated and compared between the LH and RH. We observed increased cortical thickness in the right superior temporal gyrus (STG) in the LH. A further FC analysis was conducted between the right STG and the remaining voxels in the brain. Compared with RH, the LH showed significantly higher FC in the left STG, right occipital cortex, and lower FC in the left inferior frontal gyrus and supramarginal gyrus. Our findings suggest that LH have atypical connectivity in the language network, with an enhanced role of the STG, findings which provide novel insights into the structural and functional substrates underlying the atypical language development of left-handed individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Altered neurotransmitter function in CO2-exposed stickleback (Gasterosteus aculeatus): a temperate model species for ocean acidification research.

    Science.gov (United States)

    Lai, Floriana; Jutfelt, Fredrik; Nilsson, Göran E

    2015-01-01

    Studies on the consequences of ocean acidification for the marine ecosystem have revealed behavioural changes in coral reef fishes exposed to sustained near-future CO2 levels. The changes have been linked to altered function of GABAergic neurotransmitter systems, because the behavioural alterations can be reversed rapidly by treatment with the GABAA receptor antagonist gabazine. Characterization of the molecular mechanisms involved would be greatly aided if these can be examined in a well-characterized model organism with a sequenced genome. It was recently shown that CO2-induced behavioural alterations are not confined to tropical species, but also affect the three-spined stickleback, although an involvement of the GABAA receptor was not examined. Here, we show that loss of lateralization in the stickleback can be restored rapidly and completely by gabazine treatment. This points towards a worrying universality of disturbed GABAA function after high-CO2 exposure in fishes from tropical to temperate marine habitats. Importantly, the stickleback is a model species with a sequenced and annotated genome, which greatly facilitates future studies on underlying molecular mechanisms.

  6. Limitations of a Short Demographic Questionnaire for Bedside Estimation of Patients’ Global Cognitive Functioning in Epilepsy Patients

    Directory of Open Access Journals (Sweden)

    Iris Gorny

    2018-03-01

    Full Text Available ObjectivesThe German socio-demographic estimation scale was developed by Jahn et al. (1 to quickly predict premorbid global cognitive functioning in patients. So far, it has been validated in healthy adults and has shown a good correlation with the full and verbal IQ of the Wechsler Adult Intelligence Scale (WAIS in this group. However, there are no data regarding its use as a bedside test in epilepsy patients.MethodsForty native German speaking adult patients with refractory epilepsy were included. They completed a neuropsychological assessment, including a nine scale short form of the German version of the WAIS-III and the German socio-demographic estimation scale by Jahn et al. (1 during their presurgical diagnostic stay in our center. We calculated means, correlations, and the rate of concordance (range ±5 and ±7.5 IQ score points between these two measures for the whole group, and a subsample of 19 patients with a global cognitive functioning level within 1 SD of the mean (IQ score range 85–115 and who had completed their formal education before epilepsy onset.ResultsThe German demographic estimation scale by Jahn et al. (1 showed a significant mean overestimation of the global cognitive functioning level of eight points in the epilepsy patient sample compared with the short form WAIS-III score. The accuracy within a range of ±5 or ±7.5 IQ score points for each patient was similar to that of the healthy controls reported by Jahn et al. (1 in our subsample, but not in our whole sample.ConclusionOur results show that the socio-demographic scale by Jahn et al. (1 is not sufficiently reliable as an estimation tool of global cognitive functioning in epilepsy patients. It can be used to estimate global cognitive functioning in a subset of patients with a normal global cognitive functioning level who have completed their formal education before epilepsy onset, but it does not reliably predict global cognitive functioning in epilepsy patients

  7. Altered functional connectivity differs in stroke survivors with impaired touch sensation following left and right hemisphere lesions.

    Science.gov (United States)

    Goodin, Peter; Lamp, Gemma; Vidyasagar, Rishma; McArdle, David; Seitz, Rüdiger J; Carey, Leeanne M

    2018-01-01

    One in two survivors experience impairment in touch sensation after stroke. The nature of this impairment is likely associated with changes associated with the functional somatosensory network of the brain; however few studies have examined this. In particular, the impact of lesioned hemisphere has not been investigated. We examined resting state functional connectivity in 28 stroke survivors, 14 with left hemisphere and 14 with right hemisphere lesion, and 14 healthy controls. Contra-lesional hands showed significantly decreased touch discrimination. Whole brain functional connectivity (FC) data was extracted from four seed regions, i.e. primary (S1) and secondary (S2) somatosensory cortices in both hemispheres. Whole brain FC maps and Laterality Indices (LI) were calculated for subgroups. Inter-hemispheric FC was greater in healthy controls compared to the combined stroke cohort from the left S1 seed and bilateral S2 seeds. The left lesion subgroup showed decreased FC, relative to controls, from left ipsi-lesional S1 to contra-lesional S1 and to distributed temporal, occipital and parietal regions. In comparison, the right lesion group showed decreased connectivity from contra-lesional left S1 and bilateral S2 to ipsi-lesional parietal operculum (S2), and to occipital and temporal regions. The right lesion group also showed increased intra-hemispheric FC from ipsi-lesional right S1 to inferior parietal regions compared to controls. In comparison to the left lesion group, those with right lesion showed greater intra-hemispheric connectivity from left S1 to left parietal and occipital regions and from right S1 to right angular and parietal regions. Laterality Indices were significantly greater for stroke subgroups relative to matched controls for contra-lesional S1 (left lesion group) and contra-lesional S2 (both groups). We provide evidence of altered functional connectivity within the somatosensory network, across both hemispheres, and to other networks in stroke

  8. Association between functional alterations of senescence and senility and disorders of gait and balance

    Directory of Open Access Journals (Sweden)

    Homero Teixeira-Leite

    2012-07-01

    Full Text Available OBJECTIVES: Declines in cognition and mobility are frequently observed in the elderly, and it has been suggested that the appearance of gait disorders in older individuals may constitute a marker of cognitive decline that precedes significant findings in functional performance screening tests. This study sought to evaluate the relationship between functional capacities and gait and balance in an elderly community monitored by the Preventive and Integrated Care Unit of the Hospital Adventista Silvestre in Rio de Janeiro, RJ, Brazil. METHODS: Elderly individuals (193 females and 90 males were submitted to a broad geriatric evaluation, which included the following tests: 1 a performance-oriented mobility assessment (POMA to evaluate gait; 2 a mini-mental state examination (MMSE; 3 the use of Katz and Lawton scales to assess functional capacity; 4 the application of the geriatric depression scale (GDS; and 5 a mini-nutritional assessment (MNA scale. RESULTS: Reductions in MMSE, Katz and Lawton scores were associated with reductions in POMA scores, and we also observed that significant reductions in POMA scores were present in persons for whom the MMSE and Katz scores did not clearly indicate cognitive dysfunction. We also demonstrated that a decline in the scores obtained with the GDS and MNA scales was associated with a decline in the POMA scores. CONCLUSIONS: Considering that significant alterations in the POMA scores were observed prior to the identification of significant alterations in cognitive capacity using either the MMSE or the Katz systems, a prospective study seems warranted to assess the predictive capacity of POMA scores regarding the associated decline in functional capacity.

  9. Global brands: a brief review

    Directory of Open Access Journals (Sweden)

    Martín Hernani-Merino

    2015-12-01

    Full Text Available Markets globalization has placed global brands as central players in the economic, cultural and psychological fields; the evidence is everywhere (Özsomer, Batra, Chattopadhyay & Hofstede, 2012. Therefore, many multinational companies are altering their brand portfolios in favor of global brands (Özsomer et al, 2012;. Steenkamp, Batra & Alden, 2003. Thus, this essay aims to analyze the concepts and research related to the construct of global brands. The paper seeks to understand the definition from different perspectives of what it means global brands; and later, briefly analyze the research of global branding. Finally, final considerations are discussed.

  10. Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans.

    Science.gov (United States)

    Allen, Jacob M; Mailing, Lucy J; Niemiro, Grace M; Moore, Rachel; Cook, Marc D; White, Bryan A; Holscher, Hannah D; Woods, Jeffrey A

    2018-04-01

    Exercise is associated with altered gut microbial composition, but studies have not investigated whether the gut microbiota and associated metabolites are modulated by exercise training in humans. We explored the impact of 6 wk of endurance exercise on the composition, functional capacity, and metabolic output of the gut microbiota in lean and obese adults with multiple-day dietary controls before outcome variable collection. Thirty-two lean (n = 18 [9 female]) and obese (n = 14 [11 female]), previously sedentary subjects participated in 6 wk of supervised, endurance-based exercise training (3 d·wk) that progressed from 30 to 60 min·d and from moderate (60% of HR reserve) to vigorous intensity (75% HR reserve). Subsequently, participants returned to a sedentary lifestyle activity for a 6-wk washout period. Fecal samples were collected before and after 6 wk of exercise, as well as after the sedentary washout period, with 3-d dietary controls in place before each collection. β-diversity analysis revealed that exercise-induced alterations of the gut microbiota were dependent on obesity status. Exercise increased fecal concentrations of short-chain fatty acids in lean, but not obese, participants. Exercise-induced shifts in metabolic output of the microbiota paralleled changes in bacterial genes and taxa capable of short-chain fatty acid production. Lastly, exercise-induced changes in the microbiota were largely reversed once exercise training ceased. These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent of diet and contingent on the sustainment of exercise.

  11. Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution.

    Science.gov (United States)

    Tagliazucchi, Enzo; Roseman, Leor; Kaelen, Mendel; Orban, Csaba; Muthukumaraswamy, Suresh D; Murphy, Kevin; Laufs, Helmut; Leech, Robert; McGonigle, John; Crossley, Nicolas; Bullmore, Edward; Williams, Tim; Bolstridge, Mark; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin

    2016-04-25

    Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [1]; however, because of LSD's unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally regarded as the quintessential contemporary psychedelic [2]. LSD has profound modulatory effects on consciousness and was used extensively in psychological research and psychiatric practice in the 1950s and 1960s [3]. In spite of this, however, there have been no modern human imaging studies of its acute effects on the brain. Here we studied the effects of LSD on intrinsic functional connectivity within the human brain using fMRI. High-level association cortices (partially overlapping with the default-mode, salience, and frontoparietal attention networks) and the thalamus showed increased global connectivity under the drug. The cortical areas showing increased global connectivity overlapped significantly with a map of serotonin 2A (5-HT2A) receptor densities (the key site of action of psychedelic drugs [4]). LSD also increased global integration by inflating the level of communication between normally distinct brain networks. The increase in global connectivity observed under LSD correlated with subjective reports of "ego dissolution." The present results provide the first evidence that LSD selectively expands global connectivity in the brain, compromising the brain's modular and "rich-club" organization and, simultaneously, the perceptual boundaries between the self and the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Altered frontal inter-hemispheric resting state functional connectivity is associated with bulimic symptoms among restrained eaters.

    Science.gov (United States)

    Chen, Shuaiyu; Dong, Debo; Jackson, Todd; Su, Yanhua; Chen, Hong

    2016-01-29

    Theory and research have indicated that restrained eating (RE) increases risk for binge-eating and eating disorder symptoms. According to the goal conflict model, such risk may result from disrupted hedonic-feeding control and its interaction with reward-driven eating. However, RE-related alterations in functional interactions among associated underlying brain regions, especially between the cerebral hemispheres, have rarely been examined directly. Therefore, we investigated inter-hemispheric resting-state functional connectivity (RSFC) among female restrained eaters (REs) (n=23) and unrestrained eaters (UREs) (n=24) following food deprivation as well as its relation to overall bulimia nervosa (BN) symptoms using voxel-mirrored homotopic connectivity (VMHC). Seed-based RSFC associated with areas exhibiting significant VMHC differences was also assessed. Compared to UREs, REs showed reduced VMHC in the dorsal-lateral prefrontal cortex (DLPFC), an area involved in inhibiting hedonic overeating. REs also displayed decreased RSFC between the right DLPFC and regions associated with reward estimation--the ventromedial prefrontal cortex (VMPFC) and posterior cingulate cortex (PCC). Finally, bulimic tendencies had a negative correlation with VMHC in the DLPFC and a positive correlation with functional connectivity (DLPFC and VMPFC) among REs but not UREs. Findings suggested that reduced inter-hemispheric functional connectivity in appetite inhibition regions and altered functional connectivity in reward related regions may help to explain why some REs fail to control hedonically-motivated feeding and experience higher associated levels of BN symptomatology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Altered functional resting-state hypothalamic connectivity and abnormal pituitary morphology in children with Prader-Willi syndrome.

    Science.gov (United States)

    Lukoshe, Akvile; van Dijk, Suzanne E; van den Bosch, Gerbrich E; van der Lugt, Aad; White, Tonya; Hokken-Koelega, Anita C

    2017-01-01

    Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder, characterized by endocrine problems and hyperphagia, indicating hypothalamic-pituitary dysfunction. However, few studies have explored the underlying neurobiology of the hypothalamus and its functional connectivity with other brain regions. Thus, the aim of this study was to examine the anatomical differences of the hypothalamus, mammillary bodies, and pituitary gland as well as resting state functional connectivity of the hypothalamus in children with PWS. Twenty-seven children with PWS (13 DEL, 14 mUPD) and 28 typically developing children were included. Manual segmentations by a blinded investigator were performed to determine the volumes of the hypothalamus, mammillary bodies, and pituitary gland. In addition, brain-wide functional connectivity analysis was performed using the obtained masks of the hypothalamus. Children with PWS showed altered resting state functional connectivity between hypothalamus and right and left lateral occipital complex, compared to healthy controls. In addition, children with PWS had on average a 50% smaller pituitary volume, an irregular shape of the pituitary, and a longer pituitary stalk. Pituitary volume did not increase in volume during puberty in PWS. No volumetric differences in the hypothalamus and mammillary bodies were found. In all subjects, the posterior pituitary bright spot was observed. We report altered functional hypothalamic connectivity with lateral occipital complexes in both hemispheres, which are implicated in response to food and reward system, and absence of connectivity might therefore at least partially contribute to the preoccupation with food in PWS.

  14. Going global: the functions of autobiographical memory in cultural context.

    Science.gov (United States)

    Alea, Nicole; Wang, Qi

    2015-01-01

    This special issue of Memory brings together research from around the globe, from Japanese, Chinese and East Indian cultures, to American and European societies, to the Caribbean, to Turkey and to Australia and New Zealand, which examines how and why people, from childhood to old age, remember the personal past in daily life. This journey highlights the important role of the cultural context in shaping the functional usages of autobiographical memory. We illuminate six major contributions of cross-cultural research to a broader and deeper understanding of the functions of autobiographical memory, and call attention to the filed that memory research must "go global."

  15. Functional over-redundancy and high functional vulnerability in global fish faunas on tropical reefs.

    Science.gov (United States)

    Mouillot, David; Villéger, Sébastien; Parravicini, Valeriano; Kulbicki, Michel; Arias-González, Jesus Ernesto; Bender, Mariana; Chabanet, Pascale; Floeter, Sergio R; Friedlander, Alan; Vigliola, Laurent; Bellwood, David R

    2014-09-23

    When tropical systems lose species, they are often assumed to be buffered against declines in functional diversity by the ability of the species-rich biota to display high functional redundancy: i.e., a high number of species performing similar functions. We tested this hypothesis using a ninefold richness gradient in global fish faunas on tropical reefs encompassing 6,316 species distributed among 646 functional entities (FEs): i.e., unique combinations of functional traits. We found that the highest functional redundancy is located in the Central Indo-Pacific with a mean of 7.9 species per FE. However, this overall level of redundancy is disproportionately packed into few FEs, a pattern termed functional over-redundancy (FOR). For instance, the most speciose FE in the Central Indo-Pacific contains 222 species (out of 3,689) whereas 38% of FEs (180 out of 468) have no functional insurance with only one species. Surprisingly, the level of FOR is consistent across the six fish faunas, meaning that, whatever the richness, over a third of the species may still be in overrepresented FEs whereas more than one third of the FEs are left without insurance, these levels all being significantly higher than expected by chance. Thus, our study shows that, even in high-diversity systems, such as tropical reefs, functional diversity remains highly vulnerable to species loss. Although further investigations are needed to specifically address the influence of redundant vs. vulnerable FEs on ecosystem functioning, our results suggest that the promised benefits from tropical biodiversity may not be as strong as previously thought.

  16. BP action on global warming alters political atmosphere

    International Nuclear Information System (INIS)

    Adam, P.

    1997-01-01

    British Petroleum appears to have acknowledged that the carbon dioxide emitted during the burning of fossil fuels, oils, gas and coal, may have a deleterious impact on global weather patterns and climatic conditions. This action has prompted carefully worded public responses by US-based oil companies and some nervous harrumphing in private by some of them. (Author)

  17. Structural and functional alterations of catalase induced by acriflavine, a compound causing apoptosis and necrosis.

    Science.gov (United States)

    Attar, Farnoosh; Khavari-Nejad, Sarah; Keyhani, Jacqueline; Keyhani, Ezzatollah

    2009-08-01

    Acriflavine is an antiseptic agent causing both apoptosis and necrosis in yeast. In this work, its effect on the structure and function of catalase, a vital enzyme actively involved in protection against oxidative stress, was investigated. In vitro kinetic studies showed that acriflavine inhibited the enzymatic activity in a competitive manner. The residual activity detectable after preincubation of catalase (1.5 nmol/L) with various concentrations of acriflavine went from 50% to 20% of the control value as the acriflavine concentration increased from 30 to 90 micromol/L. Correlatively with the decrease in activity, alterations in the enzyme's conformation were observed as indicated by fluorescence spectroscopy, circular dichroism spectroscopy, and electronic absorption spectroscopy. The enzyme's intrinsic fluorescence obtained upon excitation at either 297 nm (tryptophan residues) or 280 nm (tyrosine and tryptophan residues) decreased as a function of acriflavine concentration. Circular dichroism studies showed alterations of the protein structure by acriflavine with up to 13% decrease in alpha helix, 16% increase in beta-sheet content, 17% increase in random coil, and 4% increase in beta turns. Spectrophotometric studies showed a blueshift and modifications in the chromicity of catalase at 405 nm, corresponding to an absorbance band due to the enzyme's prosthetic group. Thus, acriflavine induced in vitro a profound change in the structure of catalase so that the enzyme could no longer function. Our results showed that acriflavine, a compound producing apoptosis and necrosis, can have a direct effect on vital functions in cells by disabling key enzymes.

  18. Global Asymptotic Stability of Impulsive CNNs with Proportional Delays and Partially Lipschitz Activation Functions

    Directory of Open Access Journals (Sweden)

    Xueli Song

    2014-01-01

    Full Text Available This paper researches global asymptotic stability of impulsive cellular neural networks with proportional delays and partially Lipschitz activation functions. Firstly, by means of the transformation vi(t=ui(et, the impulsive cellular neural networks with proportional delays are transformed into impulsive cellular neural networks with the variable coefficients and constant delays. Secondly, we provide novel criteria for the uniqueness and exponential stability of the equilibrium point of the latter by relative nonlinear measure and prove that the exponential stability of equilibrium point of the latter implies the asymptotic stability of one of the former. We furthermore obtain a sufficient condition to the uniqueness and global asymptotic stability of the equilibrium point of the former. Our method does not require conventional assumptions on global Lipschitz continuity, boundedness, and monotonicity of activation functions. Our results are generalizations and improvements of some existing ones. Finally, an example and its simulations are provided to illustrate the correctness of our analysis.

  19. EVALUATION OF PENALTY FUNCTIONS FOR SEMI-GLOBAL MATCHING COST AGGREGATION

    Directory of Open Access Journals (Sweden)

    C. Banz

    2012-07-01

    Full Text Available The stereo matching method semi-global matching (SGM relies on consistency constraints during the cost aggregation which are enforced by so-called penalty terms. This paper proposes new and evaluates four penalty functions for SGM. Due to mutual dependencies, two types of matching cost calculation, census and rank transform, are considered. Performance is measured using original and degenerated images exhibiting radiometric changes and noise from the Middlebury benchmark. The two best performing penalty functions are inversely proportional and negatively linear to the intensity gradient and perform equally with 6.05% and 5.91% average error, respectively. The experiments also show that adaptive penalty terms are mandatory when dealing with difficult imaging conditions. Consequently, for highest algorithmic performance in real-world systems, selection of a suitable penalty function and thorough parametrization with respect to the expected image quality is essential.

  20. Validation of a simple isotopic technique for the measurement of global and separated renal function

    International Nuclear Information System (INIS)

    Chachati, A.; Meyers, A.; Rigo, P.; Godon, J.P.

    1986-01-01

    Schlegel and Gates described an isotopic method for the measurement of global and separated glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) based on the determination by scintillation camera of the fraction of the injected dose (99mTc-DTPA-[ 131 I]hippuran) present in the kidneys 1-3 min after its administration. This method requires counting of the injected dose and attenuation correction, but no blood or urine sampling. We validated this technique by the simultaneous infusion of inulin and para-amino hippuric acid (PAH) in patients with various levels of renal function (anuric to normal). To better define individual renal function we studied 9 kidneys in patients either nephrectomized or with a nephrostomy enabling separated function measurement. A good correlation between inulin, PAH clearance, and isotopic GFR-ERPF measurement for both global and separate renal function was observed

  1. Marine ecosystems in alteration under global warming

    International Nuclear Information System (INIS)

    Prestrud, Paal

    2004-01-01

    It is commonly thought among fishermen, researchers and in the fishing industries that the administration and harvesting of the fish resources is more important for the stock of fish than are changes in the climate. However, many scientific investigations now link changes in temperature with changes in the spreading, survival and beginning of life processes. There is solid evidence that there are important changes in progress in the North Atlantic marine ecosystem caused by global warming. If the heating of the water masses continues, it will probably have a large impact on the ocean's productivity and consequently for the fishing industry

  2. Global change in the trophic functioning of marine food webs

    DEFF Research Database (Denmark)

    Maureaud, Aurore; Gascuel, Didier; Colléter, Mathieu

    2017-01-01

    and life history traits of marine species, we tested the hypothesis that anthropogenic ecological impacts may have led to changes in the global parameters defining the transfers of biomass within the food web. First, we developed two indicators to assess such changes: the Time Cumulated Indicator (TCI......The development of fisheries in the oceans, and other human drivers such as climate warming, have led to changes in species abundance, assemblages, trophic interactions, and ultimately in the functioning of marine food webs. Here, using a trophodynamic approach and global databases of catches......) measuring the residence time of biomass within the food web, and the Efficiency Cumulated Indicator (ECI) quantifying the fraction of secondary production reaching the top of the trophic chain. Then, we assessed, at the large marine ecosystem scale, the worldwide change of these two indicators over the 1950...

  3. Differences in functional brain connectivity alterations associated with cerebral amyloid deposition in amnestic mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Dahyun eYi

    2015-02-01

    Full Text Available Despite potential implications for the early detection of impending AD, very little is known about the differences of large scale brain networks between amnestic MCI (aMCI with high cerebral amyloid beta protein (Aβ deposition (i.e., aMCI+ and aMCI with no or very little Aβ deposition (i.e., aMCI-. We first aimed to extend the current literature on altering intrinsic functional connectivity (FC of the default mode network (DMN and salience network (SN from CN to AD dementia. Second, we further examined the differences of the DMN and the SN between aMCI-, aMCI+, and CN. Forty-three older adult (12 CN, 10 aMCI+, 10 aMCI-, and 11 AD dementia subjects were included. All participants received clinical and neuropsychological assessment, resting state functional MRI, structural MRI, and Pittsburgh compound-B-PET scans. FC data were preprocessed using Multivariate Exploratory Linear Optimized Decomposition into Independent Components of FSL. Group comparisons were carried out using the dual-regression approach. In addition, to verify presence of grey matter (GM volume changes with intrinsic functional network alterations, Voxel Based Morphometry was performed on the acquired T1-weighted data. As expected, AD dementia participants exhibited decreased FC in the DMN compared to CN (in precuneus and cingulate gyrus. The degree of alteration in the DMN in aMCI+ compared to CN was intermediate to that of AD. In contrast, aMCI- exhibited increased FC in the DMN compared to CN (in precuneus as well as aMCI+. In terms of the SN, aMCI- exhibited decreased FC compared to both CN and aMCI+ particularly in the inferior frontal gyrus. FC within the SN in aMCI+ and AD did not differ from CN. Compared to CN, aMCI- showed atrophy in bilateral superior temporal gyri whereas aMCI+ showed atrophy in right precuneus. The results indicate that despite of the similarity in cross-sectional cognitive features aMCI- has quite different functional brain connectivity compared to

  4. Scintigraphic Methods to Evaluate Alterations of Gastric and Esophageal Functions in Female Obesity

    Directory of Open Access Journals (Sweden)

    Özgür Ömür

    2014-02-01

    Full Text Available Objective: Altered gastrointestinal function has frequently been observed in obese patients. The aim of this study was to investigate the frequency of gastro-esophageal reflux (GER and to determine the alterations of gastric emptying and esophageal transit by scintigraphic methods in obese patients. Methods: Scintigraphic studies of 50 obese female non-diabetic patients who had not received any treatment for weight control were retrospectively reviewed. Mean Body Mass Index (BMI was 34.96±3.04 kg/m² (range:32-39 kg/m². All subjects were submitted to scintigraphic evaluation of esophageal transit, gastro-esophageal reflux, gastric emptying and presence of Helicobacter pylori infection. The data of obese patients were compared with those of sex-age matched 30 non-obese cases who were selected from our clinical archive. Results: In obese group, seventeen (34% patients were found to be GER positive scintigraphically; mean gastric emptying time (t½ was 59.18±30.8 min and the mean esophageal transit time was 8.9±7.2 s. Frequency of positive GER scintigraphy and the mean value of esophageal transit time were significantly higher in obese patients than non-obese control subjects. Gastric emptying time and esophageal transit time values were significantly longer in GER positive obese patients than GER negative ones. There was no statistically significant difference in the frequency of positive C14 urea breath test between obese and non-obese subjects and there were also no statistically significant correlations between BMI, GER, esophageal transit time and gastric emptying time. Conclusion: In our study, 42 of the 50 obese patients had esophago-gastric motility alterations. The significance of these alterations in obesity is not fully understood, but it is believed that these changes could be because of potential contributing factors in the development or maintenance of obesity or changes in eating habits

  5. Altered morphologies and functions of the olfactory bulb and hippocampus induced by miR-30c

    Directory of Open Access Journals (Sweden)

    Tingting eSun

    2016-05-01

    Full Text Available Adult neurogenesis is considered to contribute to a certain degree of plasticity for the brain. However, the effects of adult-born neurons on the brain are still largely unknown. Here, we specifically altered the expression of miR-30c in the subventricular zone (SVZ and dentate gyrus (DG by stereotaxic injection with their respective up-and down-regulated lentiviruses. Results showed an increased level of miR-30c enhanced adult neurogenesis by prompting cell-cycles of stem cells, whereas down-regulated miR-30c led to the opposite results. When these effects of miR-30c lasted for three months, we detected significant morphological changes in the olfactory bulb (OB and lineage alteration in the hippocampus. Tests of olfactory sensitivity and associative and spatial memory showed that a certain amount of adult-born neurons are essential for the normal functions of the OB and hippocampus, but there also exist redundant newborn neurons that do not further improve the functioning of these areas. Our study revealed the interactions between miRNA, adult neurogenesis, brain morphology and function, and this provides a novel insight into understanding the role of newborn neurons in the adult brain.

  6. Terrestrial Feedbacks Incorporated in Global Vegetation Models through Observed Trait-Environment Responses

    Science.gov (United States)

    Bodegom, P. V.

    2015-12-01

    Most global vegetation models used to evaluate climate change impacts rely on plant functional types to describe vegetation responses to environmental stresses. In a traditional set-up in which vegetation characteristics are considered constant within a vegetation type, the possibility to implement and infer feedback mechanisms are limited as feedback mechanisms will likely involve a changing expression of community trait values. Based on community assembly concepts, we implemented functional trait-environment relationships into a global dynamic vegetation model to quantitatively assess this feature. For the current climate, a different global vegetation distribution was calculated with and without the inclusion of trait variation, emphasizing the importance of feedbacks -in interaction with competitive processes- for the prevailing global patterns. These trait-environmental responses do, however, not necessarily imply adaptive responses of vegetation to changing conditions and may locally lead to a faster turnover in vegetation upon climate change. Indeed, when running climate projections, simulations with trait variation did not yield a more stable or resilient vegetation than those without. Through the different feedback expressions, global and regional carbon and water fluxes were -however- strongly altered. At a global scale, model projections suggest an increased productivity and hence an increased carbon sink in the next decades to come, when including trait variation. However, by the end of the century, a reduced carbon sink is projected. This effect is due to a downregulation of photosynthesis rates, particularly in the tropical regions, even when accounting for CO2-fertilization effects. Altogether, the various global model simulations suggest the critical importance of including vegetation functional responses to changing environmental conditions to grasp terrestrial feedback mechanisms at global scales in the light of climate change.

  7. Profilin-1 overexpression in MDA-MB-231 breast cancer cells is associated with alterations in proteomics biomarkers of cell proliferation, survival, and motility as revealed by global proteomics analyses.

    Science.gov (United States)

    Coumans, Joëlle V F; Gau, David; Poljak, Anne; Wasinger, Valerie; Roy, Partha; Moens, Pierre D J

    2014-12-01

    Despite early screening programs and new therapeutic strategies, metastatic breast cancer is still the leading cause of cancer death in women in industrialized countries and regions. There is a need for novel biomarkers of susceptibility, progression, and therapeutic response. Global analyses or systems science approaches with omics technologies offer concrete ways forward in biomarker discovery for breast cancer. Previous studies have shown that expression of profilin-1 (PFN1), a ubiquitously expressed actin-binding protein, is downregulated in invasive and metastatic breast cancer. It has also been reported that PFN1 overexpression can suppress tumorigenic ability and motility/invasiveness of breast cancer cells. To obtain insights into the underlying molecular mechanisms of how elevating PFN1 level induces these phenotypic changes in breast cancer cells, we investigated the alteration in global protein expression profiles of breast cancer cells upon stable overexpression of PFN1 by a combination of three different proteome analysis methods (2-DE, iTRAQ, label-free). Using MDA-MB-231 as a model breast cancer cell line, we provide evidence that PFN1 overexpression is associated with alterations in the expression of proteins that have been functionally linked to cell proliferation (FKPB1A, HDGF, MIF, PRDX1, TXNRD1, LGALS1, STMN1, LASP1, S100A11, S100A6), survival (HSPE1, HSPB1, HSPD1, HSPA5 and PPIA, YWHAZ, CFL1, NME1) and motility (CFL1, CORO1B, PFN2, PLS3, FLNA, FLNB, NME2, ARHGDIB). In view of the pleotropic effects of PFN1 overexpression in breast cancer cells as suggested by these new findings, we propose that PFN1-induced phenotypic changes in cancer cells involve multiple mechanisms. Our data reported here might also offer innovative strategies for identification and validation of novel therapeutic targets and companion diagnostics for persons with, or susceptibility to, breast cancer.

  8. Global change in the trophic functioning of marine food webs.

    Directory of Open Access Journals (Sweden)

    Aurore Maureaud

    Full Text Available The development of fisheries in the oceans, and other human drivers such as climate warming, have led to changes in species abundance, assemblages, trophic interactions, and ultimately in the functioning of marine food webs. Here, using a trophodynamic approach and global databases of catches and life history traits of marine species, we tested the hypothesis that anthropogenic ecological impacts may have led to changes in the global parameters defining the transfers of biomass within the food web. First, we developed two indicators to assess such changes: the Time Cumulated Indicator (TCI measuring the residence time of biomass within the food web, and the Efficiency Cumulated Indicator (ECI quantifying the fraction of secondary production reaching the top of the trophic chain. Then, we assessed, at the large marine ecosystem scale, the worldwide change of these two indicators over the 1950-2010 time-periods. Global trends were identified and cluster analyses were used to characterize the variability of trends between ecosystems. Results showed that the most common pattern over the study period is a global decrease in TCI, while the ECI indicator tends to increase. Thus, changes in species assemblages would induce faster and apparently more efficient biomass transfers in marine food webs. Results also suggested that the main driver of change over that period had been the large increase in fishing pressure. The largest changes occurred in ecosystems where 'fishing down the marine food web' are most intensive.

  9. Co-occurrence of communication disorder and psychiatric disorders in maltreated children and adolescents: relationship with global functioning.

    Science.gov (United States)

    Stivanin, Luciene; Oliveira, Christian C de; Santos, Fernanda P Dos; Santos, Bernardo Dos; Scivoletto, Sandra

    2016-03-01

    To study the co-occurrence of psychiatric disorders (PD) and communication disorders (CD) and their relationship with global functioning in maltreated children and adolescents. The sample comprised 143 maltreated children and adolescents (55.8% male). All underwent clinical communication and psychiatric evaluations, as well as global functioning assessment using the Children's Global Assessment Scale (C-GAS). Four groups emerged from evaluation: Group 1 (n=7, 4.9%) did not exhibit any disorders; Group 2 (n=26, 18.2%) exhibited PD; Group 3 (n=34, 23.8%) exhibited CD; and Group 4 (n=76, 53.1%) exhibited both PD and CD on evaluation. Significant differences in global functioning scores were found between G1 and G2, G1 and G4, G2 and G4, and G3 and G4, with the highest C-GAS scores found in G1 and the lowest in G4. Rates of PD and CD are high in this maltreated population. The presence of PD has a major impact on C-GAS score, and the simultaneous presence of CD increases the already impaired function of PD. Demonstration of the additive effects of PD and CD on youth functioning suggests that professionals should be alert to the presence of both disorders to better act preventively and therapeutically in a high-risk population.

  10. Predicted global warming scenarios impact on the mother plant to alter seed dormancy and germination behaviour in Arabidopsis.

    Science.gov (United States)

    Huang, Z; Footitt, S; Tang, A; Finch-Savage, W E

    2018-01-01

    Seed characteristics are key components of plant fitness that are influenced by temperature in their maternal environment, and temperature will change with global warming. To study the effect of such temperature changes, Arabidopsis thaliana plants were grown to produce seeds along a uniquely designed polyethylene tunnel having a thermal gradient reflecting local global warming predictions. Plants therefore experienced the same variations in temperature and light conditions but different mean temperatures. A range of seed-related plant fitness estimates were measured. There were dramatic non-linear temperature effects on the germination behaviour in two contrasting ecotypes. Maternal temperatures lower than 15-16 °C resulted in significantly greater primary dormancy. In addition, the impact of nitrate in the growing media on dormancy was shown only by seeds produced below 15-16 °C. However, there were no consistent effects on seed yield, number, or size. Effects on germination behaviour were shown to be a species characteristic responding to temperature and not time of year. Elevating temperature above this critical value during seed development has the potential to dramatically alter the timing of subsequent seed germination and the proportion entering the soil seed bank. This has potential consequences for the whole plant life cycle and species fitness. © 2017 John Wiley & Sons Ltd.

  11. Reduced integration and improved segregation of functional brain networks in Alzheimer's disease.

    Science.gov (United States)

    Kabbara, A; Eid, H; El Falou, W; Khalil, M; Wendling, F; Hassan, M

    2018-04-01

    Emerging evidence shows that cognitive deficits in Alzheimer's disease (AD) are associated with disruptions in brain functional connectivity. Thus, the identification of alterations in AD functional networks has become a topic of increasing interest. However, to what extent AD induces disruption of the balance of local and global information processing in the human brain remains elusive. The main objective of this study is to explore the dynamic topological changes of AD networks in terms of brain network segregation and integration. We used electroencephalography (EEG) data recorded from 20 participants (10 AD patients and 10 healthy controls) during resting state. Functional brain networks were reconstructed using EEG source connectivity computed in different frequency bands. Graph theoretical analyses were performed assess differences between both groups. Results revealed that AD networks, compared to networks of age-matched healthy controls, are characterized by lower global information processing (integration) and higher local information processing (segregation). Results showed also significant correlation between the alterations in the AD patients' functional brain networks and their cognitive scores. These findings may contribute to the development of EEG network-based test that could strengthen results obtained from currently-used neurophysiological tests in neurodegenerative diseases.

  12. Differential Functional Connectivity Alterations of Two Subdivisions within the Right dlPFC in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Julian Caspers

    2017-05-01

    Full Text Available Patients suffering from Parkinson's disease (PD often show impairments in executive function (EF like decision-making and action control. The right dorsolateral prefrontal cortex (dlPFC has been strongly implicated in EF in healthy subjects and has repeatedly been reported to show alterations related to EF impairment in PD. Recently, two key regions for cognitive action control have been identified within the right dlPFC by co-activation based parcellation. While the posterior region is engaged in rather basal EF like stimulus integration and working memory, the anterior region has a more abstract, supervisory function. To investigate whether these functionally distinct subdivisions of right dlPFC are differentially affected in PD, we analyzed resting-state functional connectivity (FC in 39 PD patients and 44 age- and gender-matched healthy controls. Patients were examined both after at least 12 h withdrawal of dopaminergic drugs (OFF and under their regular dopaminergic medication (ON. We found that only the posterior right dlPFC subdivision shows FC alterations in PD, while the anterior part remains unaffected. PD-related decreased FC with posterior right dlPFC was found in the bilateral medial posterior parietal cortex (mPPC and left dorsal premotor region (PMd in the OFF state. In the medical ON, FC with left PMd normalized, while decoupling with bilateral mPPC remained. Furthermore, we observed increased FC between posterior right dlPFC and the bilateral dorsomedial prefrontal cortex (dmPFC in PD in the ON state. Our findings point to differential disturbances of right dlPFC connectivity in PD, which relate to its hierarchical organization of EF processing by stronger affecting the functionally basal posterior aspect than the hierarchically higher anterior part.

  13. Altered intrinsic functional connectivity in the latent period of epileptogenesis in a temporal lobe epilepsy model.

    Science.gov (United States)

    Lee, Hyoin; Jung, Seungmoon; Lee, Peter; Jeong, Yong

    2017-10-01

    The latent period, a seizure-free phase, is the duration between brain injury and the onset of spontaneous recurrent seizures (SRSs) during epileptogenesis. The latent period is thought to involve several progressive pathophysiological events that lead to the evolution of the chronic epilepsy phase. Hence, it is vital to investigate the changes in the latent period during epileptogenesis in order to better understand temporal lobe epilepsy (TLE), and to achieve early diagnosis and appropriate management of the condition. Accordingly, recent studies with patients with TLE using resting-state functional magnetic resonance imaging (rs-fMRI) have reported that alterations of resting-state functional connectivity (rsFC) during the chronic period are associated with some clinical manifestations, including learning and memory impairments, emotional instability, and social behavior deficits, in addition to repetitive seizure episodes. In contrast, the changes in the intrinsic rsFC during epileptogenesis, particularly during the latent period, remain unclear. In this study, we investigated the alterations in intrinsic rsFC during the latent and chronic periods in a pilocarpine-induced TLE mouse model using intrinsic optical signal imaging (IOSI). This technique can monitor the changes in the local hemoglobin concentration according to neuronal activity and can help investigate large-scale brain intrinsic networks. After seeding on the anatomical regions of interest (ROIs) and calculating the correlation coefficients between each ROI, we established and compared functional correlation matrices and functional connectivity maps during the latent and chronic periods of epilepsy. We found a decrease in the interhemispheric rsFC at the frontal and temporal regions during both the latent and chronic periods. Furthermore, a significant decrease in the interhemispheric rsFC was observed in the somatosensory area during the chronic period. Changes in network configurations during

  14. Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder.

    Science.gov (United States)

    Cooper, Odelia; Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

    2017-06-01

    Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Prospective controlled study in an outpatient clinic. Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm 3 [standard deviation (SD), 227.3 mm 3 ] in PTSD subjects vs 835.2 mm 3 (SD, 302.8 mm 3 ) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects ( P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches.

  15. Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder

    Science.gov (United States)

    Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

    2017-01-01

    Objectives: Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Design: Prospective controlled study in an outpatient clinic. Methods: Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Results: Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm3 [standard deviation (SD), 227.3 mm3] in PTSD subjects vs 835.2 mm3 (SD, 302.8 mm3) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects (P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. Conclusions: The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches. PMID:29264511

  16. Beyond the global assessment of functioning: learning from Virginia Apgar.

    Science.gov (United States)

    Dimsdale, Joel E; Jeste, Dilip V; Patterson, Thomas L

    2010-01-01

    The Global Assessment of Functioning (GAF) scale is widely used in psychiatry, yet it has certain drawbacks. The authors seek to generate further discussion and research around developing an improved successor to the GAF. The authors used the Apgar scale as a template for constructing a possible successor to the GAF. Consulting with 16 colleagues, they selected 5 domains that were felt to be central to functioning in psychiatric patients. Psychiatrists in diverse clinical settings then completed both a GAF and a Psychiatric Apgar scale on 40 patients. The two scales were found to agree significantly. Use of the Psychiatric Apgar, however, provides clearer guidance about assessing functioning. The GAF was a brilliant addition to psychiatric practice. As we develop the next Diagnostic and Statistical Manual, it is pertinent to ask whether the GAF approach could be optimized even further by applying the lessons of Virginia Apgar.

  17. CO2 leakage alters biogeochemical and ecological functions of submarine sands

    Science.gov (United States)

    Molari, Massimiliano; Guilini, Katja; Lott, Christian; Weber, Miriam; de Beer, Dirk; Meyer, Stefanie; Ramette, Alban; Wegener, Gunter; Wenzhöfer, Frank; Martin, Daniel; Cibic, Tamara; De Vittor, Cinzia; Vanreusel, Ann; Boetius, Antje

    2018-01-01

    Subseabed CO2 storage is considered a future climate change mitigation technology. We investigated the ecological consequences of CO2 leakage for a marine benthic ecosystem. For the first time with a multidisciplinary integrated study, we tested hypotheses derived from a meta-analysis of previous experimental and in situ high-CO2 impact studies. For this, we compared ecological functions of naturally CO2-vented seafloor off the Mediterranean island Panarea (Tyrrhenian Sea, Italy) to those of nonvented sands, with a focus on biogeochemical processes and microbial and faunal community composition. High CO2 fluxes (up to 4 to 7 mol CO2 m−2 hour−1) dissolved all sedimentary carbonate, and comigration of silicate and iron led to local increases of microphytobenthos productivity (+450%) and standing stocks (+300%). Despite the higher food availability, faunal biomass (−80%) and trophic diversity were substantially lower compared to those at the reference site. Bacterial communities were also structurally and functionally affected, most notably in the composition of heterotrophs and microbial sulfate reduction rates (−90%). The observed ecological effects of CO2 leakage on submarine sands were reproduced with medium-term transplant experiments. This study assesses indicators of environmental impact by CO2 leakage and finds that community compositions and important ecological functions are permanently altered under high CO2. PMID:29441359

  18. Aberrant patterns of local and long-range functional connectivity densities in schizophrenia.

    Science.gov (United States)

    Liu, Chuanxin; Zhang, Wei; Chen, Guangdong; Tian, Hongjun; Li, Jie; Qu, Hongru; Cheng, Langlang; Zhu, Jingjing; Zhuo, Chuanjun

    2017-07-18

    Schizophrenia is a disorder of brain dysconnectivity, and both the connection strength and connection number are disrupted in patients with schizophrenia. The functional connectivity density (FCD) can reflect alterations in the connection number. Alterations in the global FCD (gFCD) in schizophrenia were previously demonstrated; however, alterations in two other indices of the pathological characteristics of the brain, local FCD (lFCD) and long-range FCD (lrFCD), have not been revealed. To investigate lFCD and lrFCD alterations in patients with schizophrenia, 95 patients and 93 matched healthy controls were examined using structural and resting-state functional magnetic resonance imaging scanning. lFCD and lrFCD were measured using FCD mapping, and differences were identified using a two-sample t-test in a voxel-wise manner, with age and gender considered to increase variability. Multiple comparisons were performed using a false discovery rate method with a corrected threshold of Pschizophrenia is a disorder of brain dysconnectivity, particularly affecting the local functional connectivity network, and support the hypothesis that schizophrenia is associated with a widespread cortical functional connectivity/activity deficit, with hyper- and/or hypo-connectivity/activity coexisting in some cortical or subcortical regions.

  19. Usefulness of zebrafish larvae to evaluate drug-induced functional and morphological renal tubular alterations.

    Science.gov (United States)

    Gorgulho, Rita; Jacinto, Raquel; Lopes, Susana S; Pereira, Sofia A; Tranfield, Erin M; Martins, Gabriel G; Gualda, Emilio J; Derks, Rico J E; Correia, Ana C; Steenvoorden, Evelyne; Pintado, Petra; Mayboroda, Oleg A; Monteiro, Emilia C; Morello, Judit

    2018-01-01

    Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir. We evaluated drug metabolic profile by mass spectrometry, renal function with the inulin clearance assay, the 3D morphology of the proximal convoluted tubule by two-photon microscopy and the ultrastructure of proximal convoluted tubule mitochondria by transmission electron microscopy. Paracetamol was metabolized by conjugation and oxidation with further detoxification with glutathione. Renal clearance was reduced with gentamicin and paracetamol. Proximal tubules were enlarged with paracetamol and tenofovir. All drugs induced mitochondrial alterations including dysmorphic shapes ("donuts", "pancakes" and "rods"), mitochondrial swelling, cristae disruption and/or loss of matrix granules. These results are in agreement with the tubular effects of gentamicin, paracetamol and tenofovir in man and demonstrate that zebrafish larvae might be a good model to assess functional and structural damage associated with DIRI.

  20. Correcting for Blood Arrival Time in Global Mean Regression Enhances Functional Connectivity Analysis of Resting State fMRI-BOLD Signals.

    Science.gov (United States)

    Erdoğan, Sinem B; Tong, Yunjie; Hocke, Lia M; Lindsey, Kimberly P; deB Frederick, Blaise

    2016-01-01

    Resting state functional connectivity analysis is a widely used method for mapping intrinsic functional organization of the brain. Global signal regression (GSR) is commonly employed for removing systemic global variance from resting state BOLD-fMRI data; however, recent studies have demonstrated that GSR may introduce spurious negative correlations within and between functional networks, calling into question the meaning of anticorrelations reported between some networks. In the present study, we propose that global signal from resting state fMRI is composed primarily of systemic low frequency oscillations (sLFOs) that propagate with cerebral blood circulation throughout the brain. We introduce a novel systemic noise removal strategy for resting state fMRI data, "dynamic global signal regression" (dGSR), which applies a voxel-specific optimal time delay to the global signal prior to regression from voxel-wise time series. We test our hypothesis on two functional systems that are suggested to be intrinsically organized into anticorrelated networks: the default mode network (DMN) and task positive network (TPN). We evaluate the efficacy of dGSR and compare its performance with the conventional "static" global regression (sGSR) method in terms of (i) explaining systemic variance in the data and (ii) enhancing specificity and sensitivity of functional connectivity measures. dGSR increases the amount of BOLD signal variance being modeled and removed relative to sGSR while reducing spurious negative correlations introduced in reference regions by sGSR, and attenuating inflated positive connectivity measures. We conclude that incorporating time delay information for sLFOs into global noise removal strategies is of crucial importance for optimal noise removal from resting state functional connectivity maps.

  1. Title: Freshwater phytoplankton responses to global warming.

    Science.gov (United States)

    Wagner, Heiko; Fanesi, Andrea; Wilhelm, Christian

    2016-09-20

    Global warming alters species composition and function of freshwater ecosystems. However, the impact of temperature on primary productivity is not sufficiently understood and water quality models need to be improved in order to assess the quantitative and qualitative changes of aquatic communities. On the basis of experimental data, we demonstrate that the commonly used photosynthetic and water chemistry parameters alone are not sufficient for modeling phytoplankton growth under changing temperature regimes. We present some new aspects of the acclimation process with respect to temperature and how contrasting responses may be explained by a more complete physiological knowledge of the energy flow from photons to new biomass. We further suggest including additional bio-markers/traits for algal growth such as carbon allocation patterns to increase the explanatory power of such models. Although carbon allocation patterns are promising and functional cellular traits for growth prediction under different nutrient and light conditions, their predictive power still waits to be tested with respect to temperature. A great challenge for the near future will be the prediction of primary production efficiencies under the global change scenario using a uniform model for phytoplankton assemblages. Copyright © 2016 Elsevier GmbH. All rights reserved.

  2. Functional alterations of V1 cortex in patients with primary open angle glaucoma using functional MRI retinotopic mapping

    International Nuclear Information System (INIS)

    Shi Linping; Cai Ping; Li Changying; Li Xueqin; Xie Bing; Li Sha; Liu Ting; Chen Xing; Shi Yanshu; Wang Jian

    2011-01-01

    Objective: To evaluate the functional changes of visual cortex (V1) in patients with primary open angle glaucoma (POAG) by fMRI retinotopic mapping technology. Methods: Fifteen POAG patients and 15 healthy volunteers underwent stimulations with fMRI retinotopic mapping stimulus and contrast-reversing checkerboard patterns stimulus on a Siemens Trio 3.0 T MRI whole-body scanner for functional data collection. Comparisons of V1 fMRI responses between the glaucomatous eyes and the healthy eyes of the patients were carried out using paired samples t-test, while independent samples t-test was used to compare V1 fMRI responses and activations between the healthy eyes of patients and the age-, gender- and side- matched eyes of normal people. Differences of V1 cortical functions and visual functions were analyzed by linear correlation analysis when the glaucomatous and the healthy eyes were simulated individually., Results: (1) V1 fMRI responses of the individually stimulated glaucomatous eyes [(1.24±0.72)%] were weaker than those of the healthy eyes [(2.18±0.93)%] (t=4.757, P 0.05). (2) Differences of V1 cortical functions were negatively correlated with those of visual functions in the individually stimulated glaucomatous and healthy eyes (r=-0.887, P< 0.01). (3) The activated area indexes of V1 cortexes in the healthy eyes from patients (0.72±0.12) were lower than those in the matched eyes of normal people (0.85±0.09) (t=-3.801, P<0.01) . Conclusion: Cortical function impairment was in accordance with visual function impairment in glaucoma. Located and quantified measurement with fMRI retinotopic mapping was a useful method for clinical follow-up and evaluation of functional alteration of glaucomatous visual cortex, and a potentially useful means of studying trans-synaptic degeneration of visual pathways of in vivo glaucoma. (authors)

  3. Global monopoles can change Universe's topology

    International Nuclear Information System (INIS)

    Marunović, Anja; Prokopec, Tomislav

    2016-01-01

    If the Universe undergoes a phase transition, at which global monopoles are created or destroyed, topology of its spatial sections can change. More specifically, by making use of Myers' theorem, we show that, after a transition in which global monopoles form, spatial sections of a spatially flat, infinite Universe becomes finite and closed. This implies that global monopoles can change the topology of Universe's spatial sections (from infinite and open to finite and closed). Global monopoles cannot alter the topology of the space-time manifold.

  4. Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity.

    Science.gov (United States)

    Wang, Junkai; Fan, Yunli; Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian

    2016-01-01

    Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity.

  5. Breast cancer cell cyclooxygenase-2 expression alters extracellular matrix structure and function and numbers of cancer associated fibroblasts.

    Science.gov (United States)

    Krishnamachary, Balaji; Stasinopoulos, Ioannis; Kakkad, Samata; Penet, Marie-France; Jacob, Desmond; Wildes, Flonne; Mironchik, Yelena; Pathak, Arvind P; Solaiyappan, Meiyappan; Bhujwalla, Zaver M

    2017-03-14

    Cyclooxygenase-2 (COX-2) is a critically important mediator of inflammation that significantly influences tumor angiogenesis, invasion, and metastasis. We investigated the role of COX-2 expressed by triple negative breast cancer cells in altering the structure and function of the extracellular matrix (ECM). COX-2 downregulation effects on ECM structure and function were investigated using magnetic resonance imaging (MRI) and second harmonic generation (SHG) microscopy of tumors derived from triple negative MDA-MB-231 breast cancer cells, and a derived clone stably expressing a short hairpin (shRNA) molecule downregulating COX-2. MRI of albumin-GdDTPA was used to characterize macromolecular fluid transport in vivo and SHG microscopy was used to quantify collagen 1 (Col1) fiber morphology. COX-2 downregulation decreased Col1 fiber density and altered macromolecular fluid transport. Immunohistochemistry identified significantly fewer activated cancer associated fibroblasts (CAFs) in low COX-2 expressing tumors. Metastatic lung nodules established by COX-2 downregulated cells were infrequent, smaller, and contained fewer Col1 fibers.COX-2 overexpression studies were performed with tumors derived from triple negative SUM-149 breast cancer cells lentivirally transduced to overexpress COX-2. SHG microscopy identified significantly higher Col1 fiber density in COX-2 overexpressing tumors with an increase of CAFs. These data expand upon the roles of COX-2 in shaping the structure and function of the ECM in primary and metastatic tumors, and identify the potential role of COX-2 in modifying the number of CAFs in tumors that may have contributed to the altered ECM.

  6. Global sensitivity analysis of computer models with functional inputs

    International Nuclear Information System (INIS)

    Iooss, Bertrand; Ribatet, Mathieu

    2009-01-01

    Global sensitivity analysis is used to quantify the influence of uncertain model inputs on the response variability of a numerical model. The common quantitative methods are appropriate with computer codes having scalar model inputs. This paper aims at illustrating different variance-based sensitivity analysis techniques, based on the so-called Sobol's indices, when some model inputs are functional, such as stochastic processes or random spatial fields. In this work, we focus on large cpu time computer codes which need a preliminary metamodeling step before performing the sensitivity analysis. We propose the use of the joint modeling approach, i.e., modeling simultaneously the mean and the dispersion of the code outputs using two interlinked generalized linear models (GLMs) or generalized additive models (GAMs). The 'mean model' allows to estimate the sensitivity indices of each scalar model inputs, while the 'dispersion model' allows to derive the total sensitivity index of the functional model inputs. The proposed approach is compared to some classical sensitivity analysis methodologies on an analytical function. Lastly, the new methodology is applied to an industrial computer code that simulates the nuclear fuel irradiation.

  7. Altered Autonomic Functions and Distressed Personality Traits in Male Adolescents with Internet Gaming Addiction.

    Science.gov (United States)

    Kim, Nahyun; Hughes, Tonda L; Park, Chang G; Quinn, Laurie; Kong, In Deok

    2016-11-01

    Internet gaming addiction (IGA) has been associated with many negative health outcomes, especially for youth; however, few studies have examined the physiological parameters and personality features related to this addiction. This study aimed to identify differences in autonomic functions and distressed (type D) personality traits among Korean adolescent males with and without IGA. In a cross-sectional study, 68 adolescent males were recruited in a Korean city using convenience and snowball sampling methods. For each subject, heart rate variability (HRV) parameters were measured as autonomic functions and questionnaires were used to identify IGA and type D personality traits. Data were analyzed using descriptive analyses, t tests, χ 2 tests, and Pearson's correlation. Most HRV parameters significantly differed between the IGA and non-IGA groups (all p gaming was related to alterations in autonomic functions and distressed personality traits in male adolescents. These findings provide further understanding of the IGA phenomenon and highlight the need for interventions that address male adolescents with IGA.

  8. Long-term oil contamination alters the molecular ecological networks of soil microbial functional genes

    Directory of Open Access Journals (Sweden)

    Yuting eLiang

    2016-02-01

    Full Text Available With knowledge on microbial composition and diversity, investigation of within-community interactions is a further step to elucidate microbial ecological functions, such as the biodegradation of hazardous contaminants. In this work, microbial functional molecular ecological networks were studied in both contaminated and uncontaminated soils to determine the possible influences of oil contamination on microbial interactions and potential functions. Soil samples were obtained from an oil-exploring site located in South China, and the microbial functional genes were analyzed with GeoChip, a high-throughput functional microarray. By building random networks based on null model, we demonstrated that overall network structures and properties were significantly different between contaminated and uncontaminated soils (P < 0.001. Network connectivity, module numbers, and modularity were all reduced with contamination. Moreover, the topological roles of the genes (module hub and connectors were altered with oil contamination. Subnetworks of genes involved in alkane and polycyclic aromatic hydrocarbon degradation were also constructed. Negative co-occurrence patterns prevailed among functional genes, thereby indicating probable competition relationships. The potential keystone genes, defined as either hubs or genes with highest connectivities in the network, were further identified. The network constructed in this study predicted the potential effects of anthropogenic contamination on microbial community co-occurrence interactions.

  9. Altering Height Data by Using Natural Logarithm as 3D Modelling Function for Reverse Engineering Application

    Science.gov (United States)

    Ilham Aminullah Abdulqawi, Nur; Salman Abu Mansor, Mohd

    2018-01-01

    The raw data extracted from reverse engineering based on vision mostly do not resemble the actual geometrical representation yet. Even though the higher object surface reflected the most visible light towards the camera and yield higher number of value based on Lambertian illumination model, this does not mean the curvature profile are always accurate. After all, there are many mathematical models to shape curvature profiles into the correct representation. However, one of the most appropriate models found is the natural logarithm function. The function itself has alteration properties towards the raw data generated from reverse engineering based on vision.

  10. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity.

    Science.gov (United States)

    Malykhina, Anna P; Lei, Qi; Erickson, Chris S; Epstein, Miles L; Saban, Marcia R; Davis, Carole A; Saban, Ricardo

    2012-12-19

    This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity.In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor.To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na(+) channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and

  11. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

    Directory of Open Access Journals (Sweden)

    Malykhina Anna P

    2012-12-01

    Full Text Available Abstract Background This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity. In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1 and cholinergic nerves (ChAT was studied one week after one or two intravesical instillations of the growth factor. To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. Results In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. Conclusions For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a

  12. Previous climatic alterations are caused by the sun

    International Nuclear Information System (INIS)

    Groenaas, Sigbjoern

    2003-01-01

    The article surveys the scientific results of previous research into the contribution of the sun to climatic alterations. The author concludes that there is evidence of eight cold periods after the last ice age and that the alterations largely were due to climate effects from the sun. However, these effects are only causing a fraction of the registered global warming. It is assumed that the human activities are contributing to the rest of the greenhouse effect

  13. Hydrologic and radiative feedbacks on extratropical transient eddies: Implications of global warming

    International Nuclear Information System (INIS)

    Gutowski, W.J. Jr.; Branscome, L.E.

    1994-01-01

    Atmospheric transient eddies contribute significantly to global energy and water cycles through their transports of sensible heat and water vapor. Changes in global climate induced by greenhouse enhancement will likely alter transient eddy behavior. General circulation models (GCMs) can simulate such alterations, but unraveling all the feedbacks that occur in GCMs is difficult

  14. Inhibition of the alpha-ketoglutarate dehydrogenase complex alters mitochondrial function and cellular calcium regulation.

    Science.gov (United States)

    Huang, Hsueh-Meei; Zhang, Hui; Xu, Hui; Gibson, Gary E

    2003-01-20

    Mitochondrial dysfunction occurs in many neurodegenerative diseases. The alpha-ketoglutarate dehydrogenase complex (KGDHC) catalyzes a key and arguably rate-limiting step of the tricarboxylic acid cycle (TCA). A reduction in the activity of the KGDHC occurs in brains and cells of patients with many of these disorders and may underlie the abnormal mitochondrial function. Abnormalities in calcium homeostasis also occur in fibroblasts from Alzheimer's disease (AD) patients and in cells bearing mutations that lead to AD. Thus, the present studies test whether the reduction of KGDHC activity can lead to the alterations in mitochondrial function and calcium homeostasis. alpha-Keto-beta-methyl-n-valeric acid (KMV) inhibits KGDHC activity in living N2a cells in a dose- and time-dependent manner. Surprisingly, concentration of KMV that inhibit in situ KGDHC by 80% does not alter the mitochondrial membrane potential (MMP). However, similar concentrations of KMV induce the release of cytochrome c from mitochondria into the cytosol, reduce basal [Ca(2+)](i) by 23% (Pcalcium release from the endoplasmic reticulum (ER) by 46% (P<0.005). This result suggests that diminished KGDHC activities do not lead to the Ca(2+) abnormalities in fibroblasts from AD patients or cells bearing PS-1 mutations. The increased release of cytochrome c with diminished KGDHC activities will be expected to activate other pathways including cell death cascades. Reductions in this key mitochondrial enzyme will likely make the cells more vulnerable to metabolic insults that promote cell death.

  15. Altered default network resting-state functional connectivity in adolescents with Internet gaming addiction.

    Directory of Open Access Journals (Sweden)

    Wei-na Ding

    Full Text Available Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA.Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS and Barratt Impulsiveness Scale-11 (BIS-11 and their hours of Internet use per week.There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours (p<0.0001 and higher CIAS (p<0.0001 and BIS-11 (p = 0.01 scores than the controls. Compared with the control group, subjects with IGA exhibited increased functional connectivity in the bilateral cerebellum posterior lobe and middle temporal gyrus. The bilateral inferior parietal lobule and right inferior temporal gyrus exhibited decreased connectivity. Connectivity with the PCC was positively correlated with CIAS scores in the right precuneus, posterior cingulate gyrus, thalamus, caudate, nucleus accumbens, supplementary motor area, and lingual gyrus. It was negatively correlated with the right cerebellum anterior lobe and left superior parietal lobule.Our results suggest that adolescents with IGA exhibit different resting-state patterns of brain activity. As these alterations are partially consistent with those in patients with substance addiction, they support the

  16. Alteration of Multiple Cell Membrane Functions in L-6 Myoblasts by T-2 Toxin: An Important Mechanism of Action.

    Science.gov (United States)

    1986-06-04

    menbrane functions. All are in a range that would in turn be expected to alter other cell functions. Intracellular LEH was reduced 10 min after T-2... Plasma amino F-id changes in guinea pigs injected with T-2 rnycotoxin. Fed. Proc. 42, 625. 20 1111" ll p J IIIý f%𔃻 11 IC IA 114 WEAVER, G.A., MW1•Z, H.J

  17. A branch and bound algorithm for the global optimization of Hessian Lipschitz continuous functions

    KAUST Repository

    Fowkes, Jaroslav M.; Gould, Nicholas I. M.; Farmer, Chris L.

    2012-01-01

    We present a branch and bound algorithm for the global optimization of a twice differentiable nonconvex objective function with a Lipschitz continuous Hessian over a compact, convex set. The algorithm is based on applying cubic regularisation

  18. Aqueous alteration of Japanese simulated waste glass P0798: Effects of alteration-phase formation on alteration rate and cesium retention

    International Nuclear Information System (INIS)

    Inagaki, Y.; Shinkai, A.; Idemistu, K.; Arima, T.; Yoshikawa, H.; Yui, M.

    2006-01-01

    Aqueous alteration tests were performed with a Japanese simulated waste glass P0798 in alkaline solutions as a function of pH or species/concentration of alkaline metals in the solution in order to evaluate the alteration conditions determining whether smectite (2:1 clay mineral) or analcime (zeolite) forms as the major alteration-phase. XRD analysis of the alteration-phases showed that smectite forms at any pH between 9.5 and 12, and analcime forms at pH above 11, though the formation also depends on species and concentrations of alkaline metals in the solution. These results cannot agree with the thermodynamically predicted phase stability, e.g., smectite is more stable than the thermodynamic prediction shows. On the basis of the results of alteration conditions, the alteration tests were performed under smectite forming conditions, where only smectite forms or no crystalline phases form, in order to evaluate the alteration rate and the mechanism of cesium release/retention. The results showed that the glass alteration proceeds slowly in proportion to square root of time under smectite forming conditions, which indicates that the alteration rate can be controlled by a diffusion process. It was suggested that the alteration rate under smectite forming conditions is independent of the pH, alkaline metal species/concentration in the solution and whether smectite actually forms or not. The results also indicated that most of cesium dissolved from the glass can be retained in the alteration-phases by reversible sorption onto smectite or irreversible incorporation into analcime, pollucite or solid solutions of them

  19. Alteration in intrinsic and extrinsic functional connectivity of resting state networks associated with subclinical hypothyroid.

    Science.gov (United States)

    Kumar, Mukesh; Modi, Shilpi; Rana, Poonam; Kumar, Pawan; Kanwar, Ratnesh; Sekhri, Tarun; D'souza, Maria; Khushu, Subash

    2018-03-05

    Subclinical hypothyroidism (SCH) is characterized by mild elevation of thyroid stimulating hormone (TSH) (range 5-10 μIU/ml) and normal free triiodothyronine (FT3) and free thyroxine (FT4). The cognitive function impairment is well known in thyroid disorders such as hypothyroidism and hyperthyroidism, but little is known about deficits in brain functions in SCH subjects. Also, whether hormone-replacement treatment is necessary or not in SCH subjects is still debatable. In order to have an insight into the cognition of SCH subjects, intrinsic and extrinsic functional connectivity (FC) of the resting state networks (RSNs) was studied. For resting state data analysis we used an unbiased, data-driven approach based on Independent Component Analysis (ICA) and dual-regression that can emphasize widespread changes in FC without restricting to a set of predefined seeds. 28 SCH subjects and 28 matched healthy controls (HC) participated in the study. RSN analysis showed significantly decreased intrinsic FC in somato-motor network (SMN) and right fronto-parietal attention network (RAN) and increased intrinsic FC in default mode network (DMN) in SCH subjects as compared to control subjects. The reduced intrinsic FC in the SMN and RAN suggests neuro-cognitive alterations in SCH subjects in the corresponding functions which were also evident from the deficit in the neuropsychological performance of the SCH subjects on behavioural tests such as digit span, delayed recall, visual retention, recognition, Bender Gestalt and Mini-Mental State Examination (MMSE). We also found a significant reduction in extrinsic network FC between DMN and RAN; SMN and posterior default mode network (PDMN); and increased extrinsic FC between SMN and anterior default mode network (ADMN) in SCH subjects as compared to controls. An altered extrinsic FC in SCH suggests functional reorganization in response to neurological disruption. The partial correlation analysis between intrinsic and extrinsic RSNs

  20. Morphological and functional alterations in adult boar epididymis: Effects of prenatal and postnatal administration of flutamide

    Directory of Open Access Journals (Sweden)

    Chojnacka Katarzyna

    2011-02-01

    Full Text Available Abstract Background The dynamic cross-talk between epididymal cells is hormonally regulated and, in part, through direct cell-to-cell interactions. To date, no information is available regarding possible impact of anti-androgens on the proteins involved in the gap junctional communication within the boar epididymis. Thus, a question arised whether prenatal or postnatal exposure to an anti-androgen flutamide alters the expression of gap junction protein - connexin43 (Cx43 and androgen receptor (AR expression in the caput, corpus and cauda epididymis and leads to delayed effects on morphology and function of adult pig epididymis. Methods First two experimental groups received flutamide prenatally on gestational days 20-28 and 80-88 (GD20 and GD80 and further two groups were exposed to flutamide postanatally on days 2-10 and 90-98 after birth (PD2 and PD90. Epididymides were collected from adult boars. Routine histology was performed using hematoxylin-eosin staining. The expression of Cx43 and AR were analyzed using immunohistochemistry and Western blotting. Both analyses were supported by quantitative approaches to demonstrate the variations of the expression levels following the treatment. Apoptotic cells were identified using TUNEL assay. Results Histological examination revealed differences in epididymal morphology of flutamide-exposed boars when compared to controls. Scarce spermatic content were seen within the corpus and cauda lumina of GD20, PD2 and PD90 groups. Concomitantly, frequency of epididymal cell apoptosis was significantly higher (p p p p Conclusions The region-specific alterations in the epididymis morphology and scarce spermatic content within the lumina of the corpus and cauda indicate that flutamide can induce delayed effects on the epididymal function of the adult boar by decrease in AR protein levels that results in altered androgen signaling. This may cause disturbances in androgen-dependent processes including Cx43

  1. The efficacy of psycho-educational group program on medication adherence and global functioning of patients with bipolar disorder type I.

    Science.gov (United States)

    Bahredar, Mohammad Jafar; Asgharnejad Farid, Ali Asghar; Ghanizadeh, Ahmad; Birashk, Behrooz

    2014-01-01

    Psycho-education is now considered as part of the integrated treatment for bipolar disorder. This study aimed to determine the efficacy of group psycho-education on medication adherence and global functioning of patients with bipolar disorder type I. 45 patients with bipolar disorder type I were allocated one of the three groups of psycho-education plus pharmacotherapy, pharmacotherapy and placebo plus pharmacotherapy. A psycho-educational program was conducted for the psycho-educational group during 9 weekly sessions. Medication adherence and global functioning of all the three groups were evaluated before the intervention, three months and six months after the intervention using Medication Adherence Rating Scale (MARS) and Global Assessment of Functioning (GAF). ANOVA was performed to examine the data. In the first and second assessments, the mean score of medication adherence and gobal functioning for patients in the psycho-educational group was significantly higher than that in the control and placebo groups (P=0.001). Medication adherence score of the psycho-educational group was increased from 6.27(0.88) to 7.92(1.38). while the mean score of the psycho-educational group increased from 56.6 (3.58) to 64.17 (2.12):, the global functioning reduced from 56.27(3.17) to 54.17(5.08) in the control group and from 56.67 (3.58) to 56 (4.36) in the placebo group. Psycho-educational program plus pharmacotherapy was effective in improvement medication adherence and global functioning of bipolar patients.

  2. Structural and functional responses of plant communities to climate change-mediated alterations in the hydrology of riparian areas in temperate Europe.

    Science.gov (United States)

    Baattrup-Pedersen, Annette; Garssen, Annemarie; Göthe, Emma; Hoffmann, Carl Christian; Oddershede, Andrea; Riis, Tenna; van Bodegom, Peter M; Larsen, Søren E; Soons, Merel

    2018-04-01

    The hydrology of riparian areas changes rapidly these years because of climate change-mediated alterations in precipitation patterns. In this study, we used a large-scale in situ experimental approach to explore effects of drought and flooding on plant taxonomic diversity and functional trait composition in riparian areas in temperate Europe. We found significant effects of flooding and drought in all study areas, the effects being most pronounced under flooded conditions. In near-stream areas, taxonomic diversity initially declined in response to both drought and flooding (although not significantly so in all years) and remained stable under drought conditions, whereas the decline continued under flooded conditions. For most traits, we found clear indications that the functional diversity also declined under flooded conditions, particularly in near-stream areas, indicating that fewer strategies succeeded under flooded conditions. Consistent changes in community mean trait values were also identified, but fewer than expected. This can have several, not mutually exclusive, explanations. First, different adaptive strategies may coexist in a community. Second, intraspecific variability was not considered for any of the traits. For example, many species can elongate shoots and petioles that enable them to survive shallow, prolonged flooding but such abilities will not be captured when applying mean trait values. Third, we only followed the communities for 3 years. Flooding excludes species intolerant of the altered hydrology, whereas the establishment of new species relies on time-dependent processes, for instance the dispersal and establishment of species within the areas. We expect that altered precipitation patterns will have profound consequences for riparian vegetation in temperate Europe. Riparian areas will experience loss of taxonomic and functional diversity and, over time, possibly also alterations in community trait responses that may have cascading effects

  3. Global Approximations to Cost and Production Functions using Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Efthymios G. Tsionas

    2009-06-01

    Full Text Available The estimation of cost and production functions in economics relies on standard specifications which are less than satisfactory in numerous situations. However, instead of fitting the data with a pre-specified model, Artificial Neural Networks (ANNs let the data itself serve as evidence to support the modelrs estimation of the underlying process. In this context, the proposed approach combines the strengths of economics, statistics and machine learning research and the paper proposes a global approximation to arbitrary cost and production functions, respectively, given by ANNs. Suggestions on implementation are proposed and empirical application relies on standard techniques. All relevant measures such as Returns to Scale (RTS and Total Factor Productivity (TFP may be computed routinely.

  4. Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats.

    Science.gov (United States)

    van den Brom, Charissa E; Boly, Chantal A; Bulte, Carolien S E; van den Akker, Rob F P; Kwekkeboom, Rick F J; Loer, Stephan A; Boer, Christa; Bouwman, R Arthur

    2016-01-01

    Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state.

  5. Performance on naturalistic virtual reality tasks depends on global cognitive functioning as assessed via traditional neurocognitive tests.

    Science.gov (United States)

    Oliveira, Jorge; Gamito, Pedro; Alghazzawi, Daniyal M; Fardoun, Habib M; Rosa, Pedro J; Sousa, Tatiana; Picareli, Luís Felipe; Morais, Diogo; Lopes, Paulo

    2017-08-14

    This investigation sought to understand whether performance in naturalistic virtual reality tasks for cognitive assessment relates to the cognitive domains that are supposed to be measured. The Shoe Closet Test (SCT) was developed based on a simple visual search task involving attention skills, in which participants have to match each pair of shoes with the colors of the compartments in a virtual shoe closet. The interaction within the virtual environment was made using the Microsoft Kinect. The measures consisted of concurrent paper-and-pencil neurocognitive tests for global cognitive functioning, executive functions, attention, psychomotor ability, and the outcomes of the SCT. The results showed that the SCT correlated with global cognitive performance as measured with the Montreal Cognitive Assessment (MoCA). The SCT explained one third of the total variance of this test and revealed good sensitivity and specificity in discriminating scores below one standard deviation in this screening tool. These findings suggest that performance of such functional tasks involves a broad range of cognitive processes that are associated with global cognitive functioning and that may be difficult to isolate through paper-and-pencil neurocognitive tests.

  6. Reductions in soil surface albedo as a function of biochar application rate: implications for global radiative forcing

    NARCIS (Netherlands)

    Verheijen, F.G.A.; Jeffery, S.L.; Velde, te M.; Penizek, V.; Beland, M.; Bastos, A.C.; Keizer, J.J.

    2013-01-01

    Biochar can be defined as pyrolysed (charred) biomass produced for application to soils with the aim of mitigating global climate change while improving soil functions. Sustainable biochar application to soils has been estimated to reduce global greenhouse gas emissions by 71-130 Pg CO2-C-e over 100

  7. Alterations of Brain Functional Architecture Associated with Psychopathic Traits in Male Adolescents with Conduct Disorder.

    Science.gov (United States)

    Pu, Weidan; Luo, Qiang; Jiang, Yali; Gao, Yidian; Ming, Qingsen; Yao, Shuqiao

    2017-09-12

    Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holistic brain-wide functional connectivity analysis, this study delineated the alterations in brain functional networks in patients with conduct disorder. Compared with matched healthy controls, we found decreased anti-synchronization between the fronto-parietal network (FPN) and default mode network (DMN), and increased intra-network synchronization within the frontothalamic-basal ganglia, right frontoparietal, and temporal/limbic/visual networks in CD patients. Correlation analysis showed that the weakened FPN-DMN interaction was associated with CU traits, while the heightened intra-network functional connectivity was related to impulsivity traits in CD patients. Our findings suggest that decoupling of cognitive control (FPN) with social understanding of others (DMN) is associated with the CU traits, and hyper-functions of the reward and motor inhibition systems elevate impulsiveness in CD.

  8. Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes

    Science.gov (United States)

    Fang, Xiefan; Mei, Wenbin; Barbazuk, William B.; Rivkees, Scott A.

    2014-01-01

    Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20–60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3–65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes. PMID:25354728

  9. A global weighted mean temperature model based on empirical orthogonal function analysis

    Science.gov (United States)

    Li, Qinzheng; Chen, Peng; Sun, Langlang; Ma, Xiaping

    2018-03-01

    A global empirical orthogonal function (EOF) model of the tropospheric weighted mean temperature called GEOFM_Tm was developed using high-precision Global Geodetic Observing System (GGOS) Atmosphere Tm data during the years 2008-2014. Due to the quick convergence of EOF decomposition, it is possible to use the first four EOF series, which consists base functions Uk and associated coefficients Pk, to represent 99.99% of the overall variance of the original data sets and its spatial-temporal variations. Results show that U1 displays a prominent latitude distribution profile with positive peaks located at low latitude region. U2 manifests an asymmetric pattern that positive values occurred over 30° in the Northern Hemisphere, and negative values were observed at other regions. U3 and U4 displayed significant anomalies in Tibet and North America, respectively. Annual variation is the major component of the first and second associated coefficients P1 and P2, whereas P3 and P4 mainly reflects both annual and semi-annual variation components. Furthermore, the performance of constructed GEOFM_Tm was validated by comparison with GTm_III and GTm_N with different kinds of data including GGOS Atmosphere Tm data in 2015 and radiosonde data from Integrated Global Radiosonde Archive (IGRA) in 2014. Generally speaking, GEOFM_Tm can achieve the same accuracy and reliability as GTm_III and GTm_N models in a global scale, even has improved in the Antarctic and Greenland regions. The MAE and RMS of GEOFM_Tm tend to be 2.49 K and 3.14 K with respect to GGOS Tm data, respectively; and 3.38 K and 4.23 K with respect to IGRA sounding data, respectively. In addition, those three models have higher precision at low latitude than middle and high latitude regions. The magnitude of Tm remains at the range of 220-300 K, presented a high correlation with geographic latitude. In the Northern Hemisphere, there was a significant enhancement at high latitude region reaching 270 K during summer

  10. Neural Alterations in Acquired Age-Related Hearing Loss

    Directory of Open Access Journals (Sweden)

    Raksha Anand Mudar

    2016-06-01

    Full Text Available Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional magnetic resonance imaging, diffusion tensor imaging, and event-related electroencephalography. We discuss structural and functional alterations observed in the temporal and frontal cortices and the limbic system. These neural alterations are discussed in the context of common cause, information-degradation, and sensory-deprivation hypotheses, and we suggest possible rehabilitation strategies. Although we are beginning to learn more about changes in neural architecture and functionality related to age-associated hearing loss, much work remains to be done. Understanding the neural alterations will provide objective markers for early identification of neural consequences of age-associated hearing loss and for evaluating benefits of intervention approaches.

  11. Assessment of global left ventricular function with dual-source computed tomography in patients with valvular heart disease

    International Nuclear Information System (INIS)

    Bak, So Hyeon; Jeon, Hae Jeong; Ko, Sung Min; Yang, Hyun Suk; Hwang, Hweung Kon; Song, Meong Gun

    2012-01-01

    Background: Left ventricular (LV) function is a vital parameter for prognosis, therapy guidance, and follow-up of cardiovascular disease. Dual-source computed tomography (DSCT) provides an accurate analysis of global LV function. Purpose: To assess the performance of DSCT in the determination of global LV functional parameters in comparison with cardiovascular magnetic resonance (CMR) and two-dimensional transthoracic echocardiography (2D-TTE) in patients with valvular heart disease (VHD). Material and Methods: A total of 111 patients (58 men, mean age 49.9 years) with known VHD and who underwent DSCT, 2D-TTE, and CMR a period of 2 weeks before undergoing valve surgery were included in this study. LV end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF) were calculated by DSCT using the threshold-based technique, by 2D-TTE using a modified Simpson's method, and by CMR using Simpson's method. Agreement for parameters of LV global function was determined with the Pearson's correlation coefficient (r) and Bland-Altman analysis. All the DSCT and CMR data-sets were assessed independently by two readers. Results: Fifty of the total 111 patients had aortic VHD, 29 patients had mitral VHD, and 32 patients had mixed aortic and mitral VHD. An excellent inter-observer agreement was seen for the assessment of global LV function using DSCT (r 0.910-0.983) and CMR (r = 0.854-0.965). An excellent or good correlation (r 0.93, 0.95, 0.87, and 0.71, respectively, P < 0.001) was noted between the DSCT and 2D-TTE values for EDV, ESV, SV, and EF. EDV (33.7 mL, P < 0.001), ESV (12.1 mL, P < 0.001), SV (21.2 mL, P < 0.001), and EF (1.6%, P = 0.019) were significantly overestimated by DSCT when compared with 2D-TTE. An excellent correlation (r = 0.96, 0.97, 0.91, and 0.94, respectively, P < 0.001) between DSCT and CMR was seen in the evaluation of EDV, ESV, SV, and EF. EDV (15.9 mL, P < 0.001), ESV (7.3 mL, P < 0.001), and SV (8.5 mL, P < 0

  12. Age-related functional brain changes in young children.

    Science.gov (United States)

    Long, Xiangyu; Benischek, Alina; Dewey, Deborah; Lebel, Catherine

    2017-07-15

    Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and global functional features, suggesting a shifting connectivity framework in early childhood. This development of functional connectivity in early childhood likely underlies major advances in cognitive abilities, including language and development of theory of mind. These findings provide important insight into the development patterns of brain function during the preschool years, and lay the foundation for future studies of altered brain development in young children with brain disorders or injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Canopy structural alterations to nitrogen functions of the soil microbial community in a Quercus virginiana forest

    Science.gov (United States)

    Moore, L. D.; Van Stan, J. T., II; Rosier, C. L.; Gay, T. E.; Wu, T.

    2014-12-01

    Forest canopy structure controls the timing, amount and chemical character of precipitation supply to soils through interception and drainage along crown surfaces. Yet, few studies have examined forest canopy structural connections to soil microbial communities (SMCs), and none have measured how this affects SMC N functions. The maritime Quercus virginiana Mill. (southern live oak) forests of St Catherine's Island, GA, USA provide an ideal opportunity to examine canopy structural alterations to SMCs and their functioning, as their throughfall varies substantially across space due to dense Tillandsia usneoides L. (spanish moss) mats bestrewn throughout. To examine the impact of throughfall variability on SMC N functions, we examined points along the canopy coverage continuum: large canopy gaps (0%), bare canopy (50-60%), and canopy of heavy T. usneoides coverage (>=85%). Five sites beneath each of the canopy cover types were monitored for throughfall water/ions and soil leachates chemistry for one storm each month over the growing period (7 months, Mar-2014 to Sep-2014) to compare with soil chemistry and SMC communities sampled every two months throughout that same period (Mar, May, Jul, Sep). DGGE and QPCR analysis of the N functioning genes (NFGs) to characterize the ammonia oxidizing bacterial (AOB-amoA), archaea (AOA-amoA), and ammonification (chiA) communities were used to determine the nitrification and decomposition potential of these microbial communities. PRS™-probes (Western Ag Innovations Inc., Saskatoon, Canada) were then used to determine the availability of NO3-N and NH4+N in the soils over a 6-week period to evaluate whether the differing NFG abundance and community structures resulted in altered N cycling.

  14. Ocean plankton. Structure and function of the global ocean microbiome.

    Science.gov (United States)

    Sunagawa, Shinichi; Coelho, Luis Pedro; Chaffron, Samuel; Kultima, Jens Roat; Labadie, Karine; Salazar, Guillem; Djahanschiri, Bardya; Zeller, Georg; Mende, Daniel R; Alberti, Adriana; Cornejo-Castillo, Francisco M; Costea, Paul I; Cruaud, Corinne; d'Ovidio, Francesco; Engelen, Stefan; Ferrera, Isabel; Gasol, Josep M; Guidi, Lionel; Hildebrand, Falk; Kokoszka, Florian; Lepoivre, Cyrille; Lima-Mendez, Gipsi; Poulain, Julie; Poulos, Bonnie T; Royo-Llonch, Marta; Sarmento, Hugo; Vieira-Silva, Sara; Dimier, Céline; Picheral, Marc; Searson, Sarah; Kandels-Lewis, Stefanie; Bowler, Chris; de Vargas, Colomban; Gorsky, Gabriel; Grimsley, Nigel; Hingamp, Pascal; Iudicone, Daniele; Jaillon, Olivier; Not, Fabrice; Ogata, Hiroyuki; Pesant, Stephane; Speich, Sabrina; Stemmann, Lars; Sullivan, Matthew B; Weissenbach, Jean; Wincker, Patrick; Karsenti, Eric; Raes, Jeroen; Acinas, Silvia G; Bork, Peer

    2015-05-22

    Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with >40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples, containing >35,000 species, we show vertical stratification with epipelagic community composition mostly driven by temperature rather than other environmental factors or geography. We identify ocean microbial core functionality and reveal that >73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems. Copyright © 2015, American Association for the Advancement of Science.

  15. Parasitism and the biodiversity-functioning relationship

    Science.gov (United States)

    Frainer, André; McKie, Brendan G.; Amundsen, Per-Arne; Knudsen, Rune; Lafferty, Kevin D.

    2018-01-01

    Biodiversity affects ecosystem functioning.Biodiversity may decrease or increase parasitism.Parasites impair individual hosts and affect their role in the ecosystem.Parasitism, in common with competition, facilitation, and predation, could regulate BD-EF relationships.Parasitism affects host phenotypes, including changes to host morphology, behavior, and physiology, which might increase intra- and interspecific functional diversity.The effects of parasitism on host abundance and phenotypes, and on interactions between hosts and the remaining community, all have potential to alter community structure and BD-EF relationships.Global change could facilitate the spread of invasive parasites, and alter the existing dynamics between parasites, communities, and ecosystems.Species interactions can influence ecosystem functioning by enhancing or suppressing the activities of species that drive ecosystem processes, or by causing changes in biodiversity. However, one important class of species interactions – parasitism – has been little considered in biodiversity and ecosystem functioning (BD-EF) research. Parasites might increase or decrease ecosystem processes by reducing host abundance. Parasites could also increase trait diversity by suppressing dominant species or by increasing within-host trait diversity. These different mechanisms by which parasites might affect ecosystem function pose challenges in predicting their net effects. Nonetheless, given the ubiquity of parasites, we propose that parasite–host interactions should be incorporated into the BD-EF framework.

  16. Global pyrogeography: the current and future distribution of wildfire.

    Directory of Open Access Journals (Sweden)

    Meg A Krawchuk

    Full Text Available Climate change is expected to alter the geographic distribution of wildfire, a complex abiotic process that responds to a variety of spatial and environmental gradients. How future climate change may alter global wildfire activity, however, is still largely unknown. As a first step to quantifying potential change in global wildfire, we present a multivariate quantification of environmental drivers for the observed, current distribution of vegetation fires using statistical models of the relationship between fire activity and resources to burn, climate conditions, human influence, and lightning flash rates at a coarse spatiotemporal resolution (100 km, over one decade. We then demonstrate how these statistical models can be used to project future changes in global fire patterns, highlighting regional hotspots of change in fire probabilities under future climate conditions as simulated by a global climate model. Based on current conditions, our results illustrate how the availability of resources to burn and climate conditions conducive to combustion jointly determine why some parts of the world are fire-prone and others are fire-free. In contrast to any expectation that global warming should necessarily result in more fire, we find that regional increases in fire probabilities may be counter-balanced by decreases at other locations, due to the interplay of temperature and precipitation variables. Despite this net balance, our models predict substantial invasion and retreat of fire across large portions of the globe. These changes could have important effects on terrestrial ecosystems since alteration in fire activity may occur quite rapidly, generating ever more complex environmental challenges for species dispersing and adjusting to new climate conditions. Our findings highlight the potential for widespread impacts of climate change on wildfire, suggesting severely altered fire regimes and the need for more explicit inclusion of fire in research

  17. Global pyrogeography: the current and future distribution of wildfire.

    Science.gov (United States)

    Krawchuk, Meg A; Moritz, Max A; Parisien, Marc-André; Van Dorn, Jeff; Hayhoe, Katharine

    2009-01-01

    Climate change is expected to alter the geographic distribution of wildfire, a complex abiotic process that responds to a variety of spatial and environmental gradients. How future climate change may alter global wildfire activity, however, is still largely unknown. As a first step to quantifying potential change in global wildfire, we present a multivariate quantification of environmental drivers for the observed, current distribution of vegetation fires using statistical models of the relationship between fire activity and resources to burn, climate conditions, human influence, and lightning flash rates at a coarse spatiotemporal resolution (100 km, over one decade). We then demonstrate how these statistical models can be used to project future changes in global fire patterns, highlighting regional hotspots of change in fire probabilities under future climate conditions as simulated by a global climate model. Based on current conditions, our results illustrate how the availability of resources to burn and climate conditions conducive to combustion jointly determine why some parts of the world are fire-prone and others are fire-free. In contrast to any expectation that global warming should necessarily result in more fire, we find that regional increases in fire probabilities may be counter-balanced by decreases at other locations, due to the interplay of temperature and precipitation variables. Despite this net balance, our models predict substantial invasion and retreat of fire across large portions of the globe. These changes could have important effects on terrestrial ecosystems since alteration in fire activity may occur quite rapidly, generating ever more complex environmental challenges for species dispersing and adjusting to new climate conditions. Our findings highlight the potential for widespread impacts of climate change on wildfire, suggesting severely altered fire regimes and the need for more explicit inclusion of fire in research on global

  18. Early endocrine alterations reflect prolonged stress and relate to one year functional outcome in patients with severe brain injury

    DEFF Research Database (Denmark)

    Marina, Djordje; Klose, Marianne; Nordenbo, Annette

    2015-01-01

    OBJECTIVE: Severe brain injury poses a risk of developing acute and chronic hypopituitarism. Pituitary hormone alterations developed in the early recovery phase after brain injury may have implications for long-term functional recovery. The objective was to assess the pattern and prevalence...

  19. Using the CARDAMOM framework to retrieve global terrestrial ecosystem functioning properties

    Science.gov (United States)

    Exbrayat, Jean-François; Bloom, A. Anthony; Smallman, T. Luke; van der Velde, Ivar R.; Feng, Liang; Williams, Mathew

    2016-04-01

    Terrestrial ecosystems act as a sink for anthropogenic emissions of fossil-fuel and thereby partially offset the ongoing global warming. However, recent model benchmarking and intercomparison studies have highlighted the non-trivial uncertainties that exist in our understanding of key ecosystem properties like plant carbon allocation and residence times. It leads to worrisome differences in terrestrial carbon stocks simulated by Earth system models, and their evolution in a warming future. In this presentation we attempt to provide global insights on these properties by merging an ecosystem model with remotely-sensed global observations of leaf area and biomass through a data-assimilation system: the CARbon Data MOdel fraMework (CARDAMOM). CARDAMOM relies on a Markov Chain Monte Carlo algorithm to retrieve confidence intervals of model parameters that regulate ecosystem properties independently of any prior land-cover information. The MCMC method thereby enables an explicit representation of the uncertainty in land-atmosphere fluxes and the evolution of terrestrial carbon stocks through time. Global experiments are performed for the first decade of the 21st century using a 1°×1° spatial resolution. Relationships emerge globally between key ecosystem properties. For example, our analyses indicate that leaf lifespan and leaf mass per area are highly correlated. Furthermore, there exists a latitudinal gradient in allocation patterns: high latitude ecosystems allocate more carbon to photosynthetic carbon (leaves) while plants invest more carbon in their structural parts (wood and root) in the wet tropics. Overall, the spatial distribution of these ecosystem properties does not correspond to usual land-cover maps and are also partially correlated with disturbance regimes. For example, fire-prone ecosystems present statistically significant higher values of carbon use efficiency than less disturbed ecosystems experiencing similar climatic conditions. These results

  20. Octreotide in Intestinal Lymphangiectasia: Lack of a Clinical Response and Failure to Alter Lymphatic Function in a Guinea Pig Model

    Directory of Open Access Journals (Sweden)

    S Makhija

    2004-01-01

    Full Text Available Intestinal lymphangiectasia, which can be classified as primary or secondary, is an unusual cause of protein-losing enteropathy. The main clinical features include edema, fat malabsorption, lymphopenia and hypoalbuminemia. Clinical management generally includes a low-fat diet and supplementation with medium chain triglycerides. A small number of recent reports advocate the use of octreotide in intestinal lymphangiectasia. It is unclear why octreotide was used in these studies; although octreotide can alter splanchnic blood flow and intestinal motility, its actions on lymphatic function has never been investigated. A case of a patient with intestinal lymphangiectasia who required a shunt procedure after failing medium chain triglycerides and octreotide therapy is presented. During the management of this case, all existing literature on intestinal lymphangiectasia and all the known actions of octreotide were reviewed. Because some of the case reports suggested that octreotide may improve the clinical course of intestinal lymphangiectasia by altering lymphatic function, a series of experiments were undertaken to assess this. In an established guinea pig model, the role of octreotide in lymphatic function was examined. In this model system, the mesenteric lymphatic vessels responded to 5-hydroxytryptamine with a decrease in constriction frequency, while histamine administration markedly increased lymphatic constriction frequency. Octreotide failed to produce any change in lymphatic function when a wide range of concentrations were applied to the mesenteric lymphatic vessel preparation. In conclusion, in this case, octreotide failed to induce a clinical response and laboratory studies showed that octreotide did not alter lymphatic function. Thus, the mechanisms by which octreotide induced clinical responses in the cases reported elsewhere in the literature remain unclear, but the present study suggests that it does not appear to act via increasing

  1. Convergent phylogenetic and functional responses to altered fire regimes in mesic savanna grasslands of North America and South Africa.

    Science.gov (United States)

    Forrestel, Elisabeth J; Donoghue, Michael J; Smith, Melinda D

    2014-08-01

    The importance of fire in the creation and maintenance of mesic grassland communities is well recognized. Improved understanding of how grasses--the dominant clade in these important ecosystems--will respond to alterations in fire regimes is needed in the face of anthropogenically driven climate and land-use change. Here, we examined how grass communities shift in response to experimentally manipulated fire regimes at multiple levels of community diversity--taxonomic, phylogenetic and functional--in C4-dominanted mesic savanna grassland sites with similar structure and physiognomy, yet disparate biogeographic histories. We found that the grass communities were similar in their phylogenetic response and aspects of their functional response to high fire frequency. Both sites exhibited phylogenetic clustering of highly abundant species in annually burned plots, driven by species of the Andropogoneae, and a narrow range of functional strategies associated with rapid post-fire regeneration in a high-light, nitrogen-limited environment. By examining multiple facets of diversity in a comparative context, we identified convergent phylogenetic and functional responses to altered fire regimes in two mesic savanna grasslands. Our results highlight the importance of a common filtering process associated with fire that is consistent across grasslands of disparate biogeographic histories and taxonomic representation. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  2. Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder.

    Science.gov (United States)

    Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

    2018-04-01

    Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC-vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder.

  3. Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder

    Science.gov (United States)

    Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

    2018-01-01

    Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC–vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder. PMID:28944772

  4. The essentials of a global index for cognitive function

    Directory of Open Access Journals (Sweden)

    Antony Joseph Mathew

    2017-09-01

    Full Text Available Cognition is comprised of the faculties: perception, creativity, intuition, and ratiocination. Optimal levels of cognition are needed for independent functioning and balanced living. With an aging population that continues to grow, dietary supplements that tilt the balance towards maintenance of cognition are being marketed for vulnerable populations facing these challenges. Randomized clinical trials provide the causal inference necessary to define the efficacy of emerging nutraceuticals. Cognition testing, in particular, requires a battery of tests that encompass all brain regions involved in cognition so as to provide endpoints necessary for product validation. The lack of well controlled studies for comparison analyses, limited sample sizes, ambiguous dosages, and poor cognitive measures result in data that cannot be compared across studies to determine the efficacy of supplements claiming to enhance cognition. Clinical trials for the nutraceutical industry should consider the multifaceted nature of supplements, where clinical endpoints must be comprehensive while remaining feasible. Combining endpoints of cognition with physiological biomarkers of immunity and metabolism to arrive at a global index for cognitive health may be necessary for claim substantiation in order to fully justify and scientifically validate improvements in cognitive health. The issues and needs of a global index will be discussed here.

  5. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    Directory of Open Access Journals (Sweden)

    Magdalena Cristóbal-García

    2015-01-01

    Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  6. Reduced integration and improved segregation of functional brain networks in Alzheimer’s disease

    Science.gov (United States)

    Kabbara, A.; Eid, H.; El Falou, W.; Khalil, M.; Wendling, F.; Hassan, M.

    2018-04-01

    Objective. Emerging evidence shows that cognitive deficits in Alzheimer’s disease (AD) are associated with disruptions in brain functional connectivity. Thus, the identification of alterations in AD functional networks has become a topic of increasing interest. However, to what extent AD induces disruption of the balance of local and global information processing in the human brain remains elusive. The main objective of this study is to explore the dynamic topological changes of AD networks in terms of brain network segregation and integration. Approach. We used electroencephalography (EEG) data recorded from 20 participants (10 AD patients and 10 healthy controls) during resting state. Functional brain networks were reconstructed using EEG source connectivity computed in different frequency bands. Graph theoretical analyses were performed assess differences between both groups. Main results. Results revealed that AD networks, compared to networks of age-matched healthy controls, are characterized by lower global information processing (integration) and higher local information processing (segregation). Results showed also significant correlation between the alterations in the AD patients’ functional brain networks and their cognitive scores. Significance. These findings may contribute to the development of EEG network-based test that could strengthen results obtained from currently-used neurophysiological tests in neurodegenerative diseases.

  7. A kind of balance between exploitation and exploration on kriging for global optimization of expensive functions

    International Nuclear Information System (INIS)

    Dong, Huachao; Song, Baowei; Wang, Peng; Huang, Shuai

    2015-01-01

    In this paper, a novel kriging-based algorithm for global optimization of computationally expensive black-box functions is presented. This algorithm utilizes a multi-start approach to find all of the local optimal values of the surrogate model and performs searches within the neighboring area around these local optimal positions. Compared with traditional surrogate-based global optimization method, this algorithm provides another kind of balance between exploitation and exploration on kriging-based model. In addition, a new search strategy is proposed and coupled into this optimization process. The local search strategy employs a kind of improved 'Minimizing the predictor' method, which dynamically adjusts search direction and radius until finds the optimal value. Furthermore, the global search strategy utilizes the advantage of kriging-based model in predicting unexplored regions to guarantee the reliability of the algorithm. Finally, experiments on 13 test functions with six algorithms are set up and the results show that the proposed algorithm is very promising.

  8. Altered Cortical Swallowing Processing in Patients with Functional Dysphagia: A Preliminary Study

    Science.gov (United States)

    Wollbrink, Andreas; Warnecke, Tobias; Winkels, Martin; Pantev, Christo; Dziewas, Rainer

    2014-01-01

    Objective Current neuroimaging research on functional disturbances provides growing evidence for objective neuronal correlates of allegedly psychogenic symptoms, thereby shifting the disease concept from a psychological towards a neurobiological model. Functional dysphagia is such a rare condition, whose pathogenetic mechanism is largely unknown. In the absence of any organic reason for a patient's persistent swallowing complaints, sensorimotor processing abnormalities involving central neural pathways constitute a potential etiology. Methods In this pilot study we measured cortical swallow-related activation in 5 patients diagnosed with functional dysphagia and a matched group of healthy subjects applying magnetoencephalography. Source localization of cortical activation was done with synthetic aperture magnetometry. To test for significant differences in cortical swallowing processing between groups, a non-parametric permutation test was afterwards performed on individual source localization maps. Results Swallowing task performance was comparable between groups. In relation to control subjects, in whom activation was symmetrically distributed in rostro-medial parts of the sensorimotor cortices of both hemispheres, patients showed prominent activation of the right insula, dorsolateral prefrontal cortex and lateral premotor, motor as well as inferolateral parietal cortex. Furthermore, activation was markedly reduced in the left medial primary sensory cortex as well as right medial sensorimotor cortex and adjacent supplementary motor area (pdysphagia - a condition with assumed normal brain function - seems to be associated with distinctive changes of the swallow-related cortical activation pattern. Alterations may reflect exaggerated activation of a widely distributed vigilance, self-monitoring and salience rating network that interferes with down-stream deglutition sensorimotor control. PMID:24586948

  9. Altered cerebro-cerebellum resting-state functional connectivity in HIV-infected male patients.

    Science.gov (United States)

    Wang, Huijuan; Li, Ruili; Zhou, Yawen; Wang, Yanming; Cui, Jin; Nguchu, Benedictor Alexander; Qiu, Bensheng; Wang, Xiaoxiao; Li, Hongjun

    2018-05-21

    In addition to the role of planning and executing movement, the cerebellum greatly contributes to cognitive process. Numerous studies have reported structural and functional abnormalities in the cerebellum for HIV-infected patients, but little is known about the altered functional connectivity of particular cerebellar subregions and the cerebrum. Therefore, this study aimed to explore the resting-state functional connectivity (rsFC) changes of the cerebellum and further analyze the relationship between the rsFC changes and the neuropsychological evaluation. The experiment involved 26 HIV-infected men with asymptomatic neurocognitive impairment (ANI) and 28 healthy controls (HC). We selected bilateral hemispheric lobule VI and lobule IX as seed regions and mapped the whole-brain rsFC for each subregion. Results revealed that right lobule VI showed significant increased rsFC with the anterior cingulate cortex (ACC) in HIV-infected subjects. In addition, the correlation analysis on HIV-infected subjects illustrated the increased rsFC was negatively correlated with the attention/working memory score. Moreover, significantly increased cerebellar rsFCs were also observed in HIV-infected patients related to right inferior frontal gyrus (IFG) and right superior medial gyrus (SMG) while decreased rsFC was just found between right lobule VI and the left hippocampus (HIP). These findings suggested that, abnormalities of cerebro-cerebellar functional connectivity might be associated with cognitive dysfunction in HIV-infected men, particularly working memory impairment. It could also be the underlying mechanism of ANI, providing further evidence for early injury in the neural substrate of HIV-infected patients.

  10. Phenotypic and Functional Alterations of Hematopoietic Stem and Progenitor Cells in an In Vitro Leukemia-Induced Microenvironment

    Directory of Open Access Journals (Sweden)

    Jean-Paul Vernot

    2017-02-01

    Full Text Available An understanding of the cell interactions occurring in the leukemic microenvironment and their functional consequences for the different cell players has therapeutic relevance. By co-culturing mesenchymal stem cells (MSC with the REH acute lymphocytic leukemia (ALL cell line, we have established an in vitro leukemic niche for the functional evaluation of hematopoietic stem/progenitor cells (HSPC, CD34+ cells. We showed that the normal homeostatic control exerted by the MSC over the HSPC is considerably lost in this leukemic microenvironment: HSPC increased their proliferation rate and adhesion to MSC. The adhesion molecules CD54 and CD44 were consequently upregulated in HSPC from the leukemic niche. Consequently, with this adhesive phenotype, HSPC showed less Stromal derived factor-1 (SDF-1-directed migration. Interestingly, multipotency was severely affected with an important reduction in the absolute count and the percentage of primitive progenitor colonies. It was possible to simulate most of these HSPC alterations by incubation of MSC with a REH-conditioned medium, suggesting that REH soluble factors and their effect on MSC are important for the observed changes. Of note, these HSPC alterations were reproduced when primary leukemic cells from an ALL type B (ALL-B patient were used to set up the leukemic niche. These results suggest that a general response is induced in the leukemic niche to the detriment of HSPC function and in favor of leukemic cell support. This in vitro leukemic niche could be a valuable tool for the understanding of the molecular events responsible for HSPC functional failure and a useful scenario for therapeutic evaluation.

  11. Cardiopulmonary Performance During Maximal Exercise in Soccer Players with Alterations in Renal Function.

    Science.gov (United States)

    Morales, Anderson Pontes; Sampaio-Jorge, Felipe; da Cruz Rangel, Luiz Felipe; de Souza Menezes, Jackson; Leite, Tiago Costa; Ribeiro, Beatriz Gonçalves

    2017-06-01

    The aim of this study was to evaluate the curves of cardiorespiratory variables during cardiopulmonary exercise testing (CPET) in soccer players who had acute alterations in the glomerular filtration rate (GFR) after performing the pre-season training protocol. Sixteen male professional soccer players (25 ± 3 years; 179 ± 2 cm; and 77 ± 6 kg) were evaluated for oxygen uptake (VO 2 ), heart rate (HR) and pulse relative oxygen (relative O 2 Pulse) curves with intervals corresponding to 10% of the total duration of CPET. Athletes were grouped according to the GFR and classified as decreased GFR (dGFR; n = 8) and normal GFR (nGFR; n = 8). Athletes from the dGFR group exhibited lower VO 2 values (p values (p values (p < 0.05) when 70% (dGFR 25.6 ± 8.4 vs. nGFR 27.9 ± 9.7 ml·beat -1 ·kg -1 ), 80% (dGFR 26.6 ± 8.8 vs. nGFR 29.1 ± 10.0 ml·beat -1 ·kg -1 ), 90% (dGFR 27.1 ± 9.0 vs. nGFR 30.8 ± 10.6 ml·beat -1 ·kg -1 ) and 100% (dGFR 28 ± 9.2 vs. nGFR 31.8 ± 10.9 ml·beat -1 ·kg -1 ) of the test was complete. A correlation was found (r = -0.66, R 2 = 0.44, p = 0.00) between lower VO 2 peak and elevated levels of urinary protein excretion. In conclusion, soccer players with reduced kidney function after performing the pre-season training protocol also presented alterations in cardiopulmonary variables. We suggest that monitoring of renal function may be used to identify less conditioned soccer players.

  12. Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Rami, E-mail: rami.haddad@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Kasneci, Amanda, E-mail: amanda.kasneci@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Mepham, Kathryn, E-mail: katherine.mepham@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Sebag, Igal A., E-mail: igal.sebag@mcgill.ca [Division of Cardiology, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); and others

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

  13. Global gene expression profile progression in Gaucher disease mouse models

    Directory of Open Access Journals (Sweden)

    Zhang Wujuan

    2011-01-01

    Full Text Available Abstract Background Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide. The pathogenic pathways resulting from lipid laden macrophages (Gaucher cells in visceral organs and their abnormal functions are obscure. Results To elucidate this pathogenic pathway, developmental global gene expression analyses were conducted in distinct Gba1 point-mutated mice (V394L/V394L and D409 V/null. About 0.9 to 3% of genes had altered expression patterns (≥ ± 1.8 fold change, representing several categories, but particularly macrophage activation and immune response genes. Time course analyses (12 to 28 wk of INFγ-regulated pro-inflammatory (13 and IL-4-regulated anti-inflammatory (11 cytokine/mediator networks showed tissue differential profiles in the lung and liver of the Gba1 mutant mice, implying that the lipid-storage macrophages were not functionally inert. The time course alterations of the INFγ and IL-4 pathways were similar, but varied in degree in these tissues and with the Gba1 mutation. Conclusions Biochemical and pathological analyses demonstrated direct relationships between the degree of tissue glucosylceramides and the gene expression profile alterations. These analyses implicate IFNγ-regulated pro-inflammatory and IL-4-regulated anti-inflammatory networks in differential disease progression with implications for understanding the Gaucher disease course and pathophysiology.

  14. Tributyltin Exposure Alters Cytokine Levels in Mouse Serum

    Science.gov (United States)

    Lawrence, Shanieek; Pellom, Samuel T.; Shanker, Anil; Whalen, Margaret M.

    2016-01-01

    Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, KC, MIP1β, MIP2 and RANTES was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40, and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in serum of mice exposed to TBT for less than 24 hr. IL1-β, IL-12βp40, IL-5 and IL-15 were also modulated in mouse serum depending on the specific experiment and the exposure concentration. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES, and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines. PMID:27602597

  15. Hematological alterations in protein malnutrition.

    Science.gov (United States)

    Santos, Ed W; Oliveira, Dalila C; Silva, Graziela B; Tsujita, Maristela; Beltran, Jackeline O; Hastreiter, Araceli; Fock, Ricardo A; Borelli, Primavera

    2017-11-01

    Protein malnutrition is one of the most serious nutritional problems worldwide, affecting 794 million people and costing up to $3.5 trillion annually in the global economy. Protein malnutrition primarily affects children, the elderly, and hospitalized patients. Different degrees of protein deficiency lead to a broad spectrum of signs and symptoms of protein malnutrition, especially in organs in which the hematopoietic system is characterized by a high rate of protein turnover and, consequently, a high rate of protein renewal and cellular proliferation. Here, the current scientific information about protein malnutrition and its effects on the hematopoietic process is reviewed. The production of hematopoietic cells is described, with special attention given to the hematopoietic microenvironment and the development of stem cells. Advances in the study of hematopoiesis in protein malnutrition are also summarized. Studies of protein malnutrition in vitro, in animal models, and in humans demonstrate several alterations that impair hematopoiesis, such as structural changes in the extracellular matrix, the hematopoietic stem cell niche, the spleen, the thymus, and bone marrow stromal cells; changes in mesenchymal and hematopoietic stem cells; increased autophagy; G0/G1 cell-cycle arrest of progenitor hematopoietic cells; and functional alterations in leukocytes. Structural and cellular changes of the hematopoietic microenvironment in protein malnutrition contribute to bone marrow atrophy and nonestablishment of hematopoietic stem cells, resulting in impaired homeostasis and an impaired immune response. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Globally conformal invariant gauge field theory with rational correlation functions

    CERN Document Server

    Nikolov, N M; Todorov, I T; CERN. Geneva; Todorov, Ivan T.

    2003-01-01

    Operator product expansions (OPE) for the product of a scalar field with its conjugate are presented as infinite sums of bilocal fields $V_{\\kappa} (x_1, x_2)$ of dimension $(\\kappa, \\kappa)$. For a {\\it globally conformal invariant} (GCI) theory we write down the OPE of $V_{\\kappa}$ into a series of {\\it twist} (dimension minus rank) $2\\kappa$ symmetric traceless tensor fields with coefficients computed from the (rational) 4-point function of the scalar field. We argue that the theory of a GCI hermitian scalar field ${\\cal L} (x)$ of dimension 4 in $D = 4$ Minkowski space such that the 3-point functions of a pair of ${\\cal L}$'s and a scalar field of dimension 2 or 4 vanish can be interpreted as the theory of local observables of a conformally invariant fixed point in a gauge theory with Lagrangian density ${\\cal L} (x)$.

  17. Adult onset global loss of the fto gene alters body composition and metabolism in the mouse.

    Directory of Open Access Journals (Sweden)

    Fiona McMurray

    Full Text Available The strongest BMI-associated GWAS locus in humans is the FTO gene. Rodent studies demonstrate a role for FTO in energy homeostasis and body composition. The phenotypes observed in loss of expression studies are complex with perinatal lethality, stunted growth from weaning, and significant alterations in body composition. Thus understanding how and where Fto regulates food intake, energy expenditure, and body composition is a challenge. To address this we generated a series of mice with distinct temporal and spatial loss of Fto expression. Global germline loss of Fto resulted in high perinatal lethality and a reduction in body length, fat mass, and lean mass. When ratio corrected for lean mass, mice had a significant increase in energy expenditure, but more appropriate multiple linear regression normalisation showed no difference in energy expenditure. Global deletion of Fto after the in utero and perinatal period, at 6 weeks of age, removed the high lethality of germline loss. However, there was a reduction in weight by 9 weeks, primarily as loss of lean mass. Over the subsequent 10 weeks, weight converged, driven by an increase in fat mass. There was a switch to a lower RER with no overall change in food intake or energy expenditure. To test if the phenotype can be explained by loss of Fto in the mediobasal hypothalamus, we sterotactically injected adeno-associated viral vectors encoding Cre recombinase to cause regional deletion. We observed a small reduction in food intake and weight gain with no effect on energy expenditure or body composition. Thus, although hypothalamic Fto can impact feeding, the effect of loss of Fto on body composition is brought about by its actions at sites elsewhere. Our data suggest that Fto may have a critical role in the control of lean mass, independent of its effect on food intake.

  18. A global analysis of recent experimental results: How well determined are the parton distribution functions?

    International Nuclear Information System (INIS)

    Morfin, J.G.

    1990-08-01

    Following is a brief summary of the results of an analysis of experimental data performed to extract the patron distribution functions. In contrast to other global analyses, this study investigated how the fit results depend on: Experimental Systematic Errors; Kinematic Cuts on the Analyzed Data and Choice of Initial Functional Forms, with a prime goal being a close look at the range of low-x behavior allowed by data. This is crucial for predictions for the SSC/LHC, HERA, and even at Tevatron Collider energies. Since all details can be found in the just released Fermilab preprint Parton Distributions from a Global QCD Analysis of Deep Inelastic Scattering and Lepton-Pair Production by J. G. M. and Wu-Ki Tung, this summary will be only a brief outline of major results. 11 refs., 13 figs

  19. The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function.

    Science.gov (United States)

    Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

    2017-01-01

    Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB 1 receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.5μg/kg/infusion) intravenously. After reaching stable drug intake, self-administration behavior was extinguished to examine drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral parameters presumed to influence drug-taking and drug-seeking behaviors were examined to gain more insight into the behavioral specificity of nandrolone treatment. Finally, animals were sacrificed for analysis of CB 1 receptor density and function in selected brain areas. We found that nandrolone-treated rats self-administered up to 2 times more cannabinoid than vehicle-treated rats, but behaved similarly to control rats when tested for drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by nandrolone-treated rats was not accompanied by changes in locomotor activity, sensorimotor gating, or memory function. However, our molecular data show that after chronic WIN self-administration nandrolone-treated rats display altered CB 1 receptor density and function in selected brain areas. We hypothesize that increased cannabinoid self-administration in nandrolone-treated rats results from a nandrolone-induced decrease in reward function, which rats seem to compensate by voluntarily increasing their cannabinoid intake. Altogether, our findings corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids induces dysfunction of the reward pathway in rats and might represent a potential risk factor for abuse of

  20. Alterations in brain metabolism and function following administration of low-dose codeine phosphate: 1H-magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging studies

    OpenAIRE

    Cao, Zhen; Lin, Pei-Yin; Shen, Zhi-Wei; Wu, Ren-Hua; Xiao, Ye-Yu

    2016-01-01

    The aim of the present study was to identify alterations in brain function following administration of a single, low-dose of codeine phosphate in healthy volunteers using resting-state functional magnetic resonance imaging (fMRI). In addition, the metabolic changes in the two sides of the frontal lobe were identified using 1H-magnetic resonance spectroscopy (1H-MRS). A total of 20 right-handed healthy participants (10 males, 10 females) were evaluated, and a Signa HDx 1.5T MRI scanner was use...

  1. On convergence of differential evolution over a class of continuous functions with unique global optimum.

    Science.gov (United States)

    Ghosh, Sayan; Das, Swagatam; Vasilakos, Athanasios V; Suresh, Kaushik

    2012-02-01

    Differential evolution (DE) is arguably one of the most powerful stochastic real-parameter optimization algorithms of current interest. Since its inception in the mid 1990s, DE has been finding many successful applications in real-world optimization problems from diverse domains of science and engineering. This paper takes a first significant step toward the convergence analysis of a canonical DE (DE/rand/1/bin) algorithm. It first deduces a time-recursive relationship for the probability density function (PDF) of the trial solutions, taking into consideration the DE-type mutation, crossover, and selection mechanisms. Then, by applying the concepts of Lyapunov stability theorems, it shows that as time approaches infinity, the PDF of the trial solutions concentrates narrowly around the global optimum of the objective function, assuming the shape of a Dirac delta distribution. Asymptotic convergence behavior of the population PDF is established by constructing a Lyapunov functional based on the PDF and showing that it monotonically decreases with time. The analysis is applicable to a class of continuous and real-valued objective functions that possesses a unique global optimum (but may have multiple local optima). Theoretical results have been substantiated with relevant computer simulations.

  2. Assessment of global left ventricular function with dual-source computed tomography in patients with valvular heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Bak, So Hyeon; Jeon, Hae Jeong (Dept. of Radiology, Konkuk Univ. Hospital, Konkuk Univ. School of Medicine, Seoul (Korea, Republic of)); Ko, Sung Min (Dept. of Radiology, Konkuk Univ. Hospital, Konkuk Univ. School of Medicine, Seoul (Korea, Republic of); Research Inst. of Medical Science, Konkuk Univ. Hospital, Konkuk Univ. School of Medicine, Seoul (Korea, Republic of)), Email: 20070437@kuh.ac.kr; Yang, Hyun Suk; Hwang, Hweung Kon (Dept. of Cardiology, Konkuk Univ. Hospital, Konkuk Univ. School of Medicine, Seoul (Korea, Republic of)); Song, Meong Gun (Dept. of Thoracic Surgery, Konkuk Univ. Hospital, Konkuk Univ. School of Medicine, Seoul (Korea, Republic of))

    2012-04-15

    Background: Left ventricular (LV) function is a vital parameter for prognosis, therapy guidance, and follow-up of cardiovascular disease. Dual-source computed tomography (DSCT) provides an accurate analysis of global LV function. Purpose: To assess the performance of DSCT in the determination of global LV functional parameters in comparison with cardiovascular magnetic resonance (CMR) and two-dimensional transthoracic echocardiography (2D-TTE) in patients with valvular heart disease (VHD). Material and Methods: A total of 111 patients (58 men, mean age 49.9 years) with known VHD and who underwent DSCT, 2D-TTE, and CMR a period of 2 weeks before undergoing valve surgery were included in this study. LV end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF) were calculated by DSCT using the threshold-based technique, by 2D-TTE using a modified Simpson's method, and by CMR using Simpson's method. Agreement for parameters of LV global function was determined with the Pearson's correlation coefficient (r) and Bland-Altman analysis. All the DSCT and CMR data-sets were assessed independently by two readers. Results: Fifty of the total 111 patients had aortic VHD, 29 patients had mitral VHD, and 32 patients had mixed aortic and mitral VHD. An excellent inter-observer agreement was seen for the assessment of global LV function using DSCT (r 0.910-0.983) and CMR (r = 0.854-0.965). An excellent or good correlation (r 0.93, 0.95, 0.87, and 0.71, respectively, P < 0.001) was noted between the DSCT and 2D-TTE values for EDV, ESV, SV, and EF. EDV (33.7 mL, P < 0.001), ESV (12.1 mL, P < 0.001), SV (21.2 mL, P < 0.001), and EF (1.6%, P = 0.019) were significantly overestimated by DSCT when compared with 2D-TTE. An excellent correlation (r = 0.96, 0.97, 0.91, and 0.94, respectively, P < 0.001) between DSCT and CMR was seen in the evaluation of EDV, ESV, SV, and EF. EDV (15.9 mL, P < 0.001), ESV (7.3 mL, P < 0.001), and SV

  3. Detached and distracted: ERP correlates of altered attentional function in depersonalisation.

    Science.gov (United States)

    Schabinger, Nadine; Gillmeister, Helge; Berti, Stefan; Michal, Matthias; Beutel, Manfred E; Adler, Julia

    2018-04-01

    Depersonalisation (DP) is a psychological condition marked by feelings of disembodiment. In everyday life, it is frequently associated with concentration problems. The present study used visual event-related potentials (ERPs) in a Posner-type spatial cueing task with valid, invalid and spatially neutral cues to delineate the potential neurophysiological correlates of these concentration problems. Altered attentional functioning at early, sensory stages was found in DP patients but not in anxiety- and depression-matched psychosomatic patients without DP. Specifically, DP was associated with decreased suppression of stimuli at unattended locations, shown as absent processing costs for invalidly versus neutrally cued stimuli over P1 (135-150 ms). Attentional benefits at N1, and all attentional effects at later, cognitive processing stages (P2-N2, P3) were similar in both groups. We propose that this insufficient early suppression of unattended stimuli may result from atypical sensory gain control in DP. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity.

    Science.gov (United States)

    Cissé, Yasmine M; Russart, Kathryn L G; Nelson, Randy J

    2017-03-31

    Exposure to dim light at night (dLAN) disrupts natural light/dark cycles and impairs endogenous circadian rhythms necessary to maintain optimal biological function, including the endocrine and immune systems. We have previously demonstrated that white dLAN compromises innate and cell mediated immune responses in adult Siberian hamsters (Phodopus sungorus). We hypothesized that dLAN has transgenerational influences on immune function. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 9 weeks, then paired in full factorial design, mated, and thereafter housed under dark nights. Offspring were gestated and reared in dark nights, then tested as adults for cell-mediated and humoral immunity. Maternal exposure to dLAN dampened delayed type hypersensitivity (DTH) responses in male offspring. Maternal and paternal exposure to dLAN reduced DTH responses in female offspring. IgG antibodies to a novel antigen were elevated in offspring of dams exposed to dLAN. Paternal exposure to dLAN decreased splenic endocrine receptor expression and global methylation in a parental sex-specific manner. Together, these data suggest that exposure to dLAN has transgenerational effects on endocrine-immune function that may be mediated by global alterations in the epigenetic landscape of immune tissues.

  5. Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Schizophrenia.

    Science.gov (United States)

    Zhu, Jiajia; Zhuo, Chuanjun; Xu, Lixue; Liu, Feng; Qin, Wen; Yu, Chunshui

    2017-10-21

    Respective changes in resting-state cerebral blood flow (CBF) and functional connectivity in schizophrenia have been reported. However, their coupling alterations in schizophrenia remain largely unknown. 89 schizophrenia patients and 90 sex- and age-matched healthy controls underwent resting-state functional MRI to calculate functional connectivity strength (FCS) and arterial spin labeling imaging to compute CBF. The CBF-FCS coupling of the whole gray matter and the CBF/FCS ratio (the amount of blood supply per unit of connectivity strength) of each voxel were compared between the 2 groups. Whole gray matter CBF-FCS coupling was decreased in schizophrenia patients relative to healthy controls. In schizophrenia patients, the decreased CBF/FCS ratio was predominantly located in cognitive- and emotional-related brain regions, including the dorsolateral prefrontal cortex, insula, hippocampus and thalamus, whereas an increased CBF/FCS ratio was mainly identified in the sensorimotor regions, including the putamen, and sensorimotor, mid-cingulate and visual cortices. These findings suggest that the neurovascular decoupling in the brain may be a possible neuropathological mechanism of schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

  6. The evolution of the global stellar mass function of star clusters: an analytic description

    NARCIS (Netherlands)

    Lamers, H.J.G.L.M.; Baumgardt, H.; Gieles, M.

    2013-01-01

    The evolution of the global stellar mass function of star clusters is studied based on a large set of N-body simulations of clusters with a range of initial masses, initial concentrations, in circular or elliptical orbits in different tidal environments. Models with and without initial mass

  7. Alterations in cardiomyocyte function after pulmonary treatment with stainless steel welding fume in rats.

    Science.gov (United States)

    Popstojanov, Risto; Antonini, James M; Salmen, Rebecca; Ye, Morgan; Zheng, Wen; Castranova, Vincent; Fekedulegn, Desta B; Kan, Hong

    2014-01-01

    Welding fume is composed of a complex of different metal particulates. Pulmonary exposure to different welding fumes may exert a negative impact on cardiac function, although the underlying mechanisms remain unclear. To explore the effect of welding fumes on cardiac function, Sprague-Dawley rats were exposed by intratracheal instillation to 2 mg/rat of manual metal arc hard surfacing welding fume (MMA-HS) once per week for 7 wk. Control rats received saline. Cardiomyocytes were isolated enzymatically at d 1 and 7 postexposure. Intracellular calcium ([Ca(2+)]i) transients (fluorescence ratio) were measured on the stage of an inverted phase-contrast microscope using a myocyte calcium imaging/cell length system. Phosphorylation levels of cardiac troponin I (cTnI) were determined by Western blot. The levels of nonspecific inflammatory marker C-reactive protein (CRP) and proinflammatory cytokine interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA). Contraction of isolated cardiomyocytes was significantly reduced at d 1 and d 7 postexposure. Intracellular calcium levels were decreased in response to extracellular calcium stimulation at d 7 postexposure. Changes of intracellular calcium levels after isoprenaline hydrochloride (ISO) stimulation were not markedly different between groups at either time point. Phosphorylation levels of cTnI in the left ventricle were significantly lower at d 1 postexposure. The serum levels of CRP were not markedly different between groups at either time point. Serum levels of IL-6 were not detectable in both groups. Cardiomyocyte alterations observed after welding fume treatment were mainly due to alterations in intracellular calcium handling and phosphorylation levels of cTnI.

  8. No Evidence that Infection Alters Global Recombination Rate in House Mice.

    Directory of Open Access Journals (Sweden)

    Beth L Dumont

    Full Text Available Recombination rate is a complex trait, with genetic and environmental factors shaping observed patterns of variation. Although recent studies have begun to unravel the genetic basis of recombination rate differences between organisms, less attention has focused on the environmental determinants of crossover rates. Here, we test the effect of one ubiquitous environmental pressure-bacterial infection-on global recombination frequency in mammals. We applied MLH1 mapping to assay global crossover rates in male mice infected with the pathogenic bacterium Borrelia burgdorferi, the causative agent of Lyme Disease, and uninfected control animals. Despite ample statistical power to identify biologically relevant differences between infected and uninfected animals, we find no evidence for a global recombination rate response to bacterial infection. Moreover, broad-scale patterns of crossover distribution, including the number of achiasmate bivalents, are not affected by infection status. Although pathogen exposure can plastically increase recombination in some species, our findings suggest that recombination rates in house mice may be resilient to at least some forms of infection stress. This negative result motivates future experiments with alternative house mouse pathogens to evaluate the generality of this conclusion.

  9. Neuroimaging meta-analysis of cannabis use studies reveals convergent functional alterations in brain regions supporting cognitive control and reward processing.

    Science.gov (United States)

    Yanes, Julio A; Riedel, Michael C; Ray, Kimberly L; Kirkland, Anna E; Bird, Ryan T; Boeving, Emily R; Reid, Meredith A; Gonzalez, Raul; Robinson, Jennifer L; Laird, Angela R; Sutherland, Matthew T

    2018-03-01

    Lagging behind rapid changes to state laws, societal views, and medical practice is the scientific investigation of cannabis's impact on the human brain. While several brain imaging studies have contributed important insight into neurobiological alterations linked with cannabis use, our understanding remains limited. Here, we sought to delineate those brain regions that consistently demonstrate functional alterations among cannabis users versus non-users across neuroimaging studies using the activation likelihood estimation meta-analysis framework. In ancillary analyses, we characterized task-related brain networks that co-activate with cannabis-affected regions using data archived in a large neuroimaging repository, and then determined which psychological processes may be disrupted via functional decoding techniques. When considering convergent alterations among users, decreased activation was observed in the anterior cingulate cortex, which co-activated with frontal, parietal, and limbic areas and was linked with cognitive control processes. Similarly, decreased activation was observed in the dorsolateral prefrontal cortex, which co-activated with frontal and occipital areas and linked with attention-related processes. Conversely, increased activation among users was observed in the striatum, which co-activated with frontal, parietal, and other limbic areas and linked with reward processing. These meta-analytic outcomes indicate that cannabis use is linked with differential, region-specific effects across the brain.

  10. Globally COnstrained Local Function Approximation via Hierarchical Modelling, a Framework for System Modelling under Partial Information

    DEFF Research Database (Denmark)

    Øjelund, Henrik; Sadegh, Payman

    2000-01-01

    be obtained. This paper presents a new approach for system modelling under partial (global) information (or the so called Gray-box modelling) that seeks to perserve the benefits of the global as well as local methodologies sithin a unified framework. While the proposed technique relies on local approximations......Local function approximations concern fitting low order models to weighted data in neighbourhoods of the points where the approximations are desired. Despite their generality and convenience of use, local models typically suffer, among others, from difficulties arising in physical interpretation...... simultaneously with the (local estimates of) function values. The approach is applied to modelling of a linear time variant dynamic system under prior linear time invariant structure where local regression fails as a result of high dimensionality....

  11. Altered cingulo-striatal function underlies reward drive deficits in schizophrenia.

    Science.gov (United States)

    Park, Il Ho; Chun, Ji Won; Park, Hae-Jeong; Koo, Min-Seong; Park, Sunyoung; Kim, Seok-Hyeong; Kim, Jae-Jin

    2015-02-01

    Amotivation in schizophrenia is assumed to involve dysfunctional dopaminergic signaling of reward prediction or anticipation. It is unclear, however, whether the translation of neural representation of reward value to behavioral drive is affected in schizophrenia. In order to examine how abnormal neural processing of response valuation and initiation affects incentive motivation in schizophrenia, we conducted functional MRI using a deterministic reinforcement learning task with variable intervals of contingency reversals in 20 clinically stable patients with schizophrenia and 20 healthy controls. Behaviorally, the advantage of positive over negative reinforcer in reinforcement-related responsiveness was not observed in patients. Patients showed altered response valuation and initiation-related striatal activity and deficient rostro-ventral anterior cingulate cortex activation during reward approach initiation. Among these neural abnormalities, rostro-ventral anterior cingulate cortex activation was correlated with positive reinforcement-related responsiveness in controls and social anhedonia and social amotivation subdomain scores in patients. Our findings indicate that the central role of the anterior cingulate cortex is in translating action value into driving force of action, and underscore the role of the cingulo-striatal network in amotivation in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Providing Global Change Information for Decision-Making: Capturing and Presenting Provenance

    Science.gov (United States)

    Ma, Xiaogang; Fox, Peter; Tilmes, Curt; Jacobs, Katherine; Waple, Anne

    2014-01-01

    Global change information demands access to data sources and well-documented provenance to provide evidence needed to build confidence in scientific conclusions and, in specific applications, to ensure the information's suitability for use in decision-making. A new generation of Web technology, the Semantic Web, provides tools for that purpose. The topic of global change covers changes in the global environment (including alterations in climate, land productivity, oceans or other water resources, atmospheric composition and or chemistry, and ecological systems) that may alter the capacity of the Earth to sustain life and support human systems. Data and findings associated with global change research are of great public, government, and academic concern and are used in policy and decision-making, which makes the provenance of global change information especially important. In addition, since different types of decisions benefit from different types of information, understanding how to capture and present the provenance of global change information is becoming more of an imperative in adaptive planning.

  13. Dynamic alteration in splenic function during acute falciparum malaria

    International Nuclear Information System (INIS)

    Looareesuwan, S.; Ho, M.; Wattanagoon, Y.; White, N.J.; Warrell, D.A.; Bunnag, D.; Harinasuta, T.; Wyler, D.J.

    1987-01-01

    Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated 51 Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes [mean +/- SD] vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than did the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies

  14. Globalization

    OpenAIRE

    Andru?cã Maria Carmen

    2013-01-01

    The field of globalization has highlighted an interdependence implied by a more harmonious understanding determined by the daily interaction between nations through the inducement of peace and the management of streamlining and the effectiveness of the global economy. For the functioning of the globalization, the developing countries that can be helped by the developed ones must be involved. The international community can contribute to the institution of the development environment of the gl...

  15. Alterations of White Matter Connectivity in Preschool Children with Autism Spectrum Disorder.

    Science.gov (United States)

    Li, Shi-Jun; Wang, Yi; Qian, Long; Liu, Gang; Liu, Shuang-Feng; Zou, Li-Ping; Zhang, Ji-Shui; Hu, Nan; Chen, Xiao-Qiao; Yu, Sheng-Yuan; Guo, Sheng-Li; Li, Ke; He, Mian-Wang; Wu, Hai-Tao; Qiu, Jiang-Xia; Zhang, Lei; Wang, Yu-Lin; Lou, Xin; Ma, Lin

    2018-03-27

    Purpose To investigate the topologic architecture of white matter connectivity networks in preschool-aged children with a diagnosis of autism spectrum disorder (ASD) versus typical development (TD). Materials and Methods Forty-two participants were enrolled, including 21 preschool children with ASD (14 male children and seven female children; mean age, 4.56 years ± 0.97 [standard deviation]) and 21 children with TD (11 males and 10 females; mean age, 5.13 years ± 0.82). The diagnosis of ASD was determined according to the Diagnostic and Statistical Manual of Mental Disorders Global Assessment of Functioning scores (mean score, 8.00 ± 0.50). All participants underwent diffusion-tensor imaging (DTI) and T2-weighted imaging on a 3-T magnetic resonance system. A graph theoretical analysis was applied to investigate the topologic organization of the brain network including global and local topologic parameters. Statistical analysis was then performed for the comparison between the groups. Results Compared with the TD group, children with ASD demonstrated shortened characteristic path length (t 1 = 0.536, t 2 = 0.534, t 3 = 0.523, t 4 = 0.510, and t 5 = 0.501; P < .05) and increased global efficiency (t 1 = 0.499, t 2 = 0.497, t 3 = 0.486, t 4 = 0.473, and t 5 = 0.465; P < .05) and clustering coefficient (t 1 = 0.673, t 2 = 0.750, t 3 = 0.757, t 4 = 0.738, and t 5 = 0.741; P < .05). Significant increases in nodal efficiency were mainly found in left pallidum (0.037 vs 0.032, respectively; P < .01) and right caudate nucleus (0.037 vs 0.032, respectively; P < .01) of the basal ganglia network. Conclusion Significantly altered patterns of global and local brain network topography may underlie the abnormal brain development in preschool children with ASD compared with those who have TD. The identification of altered structural connectivity in basal ganglia and paralimbic-limbic networks may point toward potential imaging biomarkers for preschool-age patients with ASD.

  16. Chronic cannabis users show altered neurophysiological functioning on Stroop task conflict resolution.

    Science.gov (United States)

    Battisti, Robert A; Roodenrys, Steven; Johnstone, Stuart J; Pesa, Nicole; Hermens, Daniel F; Solowij, Nadia

    2010-12-01

    Chronic cannabis use has been related to deficits in cognition (particularly memory) and the normal functioning of brain structures sensitive to cannabinoids. There is increasing evidence that conflict monitoring and resolution processes (i.e. the ability to detect and respond to change) may be affected. This study examined the ability to inhibit an automatic reading response in order to activate a more difficult naming response (i.e. conflict resolution) in a variant of the discrete trial Stroop colour-naming task. Event-related brain potentials to neutral, congruent and incongruent trials were compared between 21 cannabis users (mean 16.4 years of near daily use) in the unintoxicated state and 19 non-using controls. Cannabis users showed increased errors on colour-incongruent trials (e.g. "RED" printed in blue ink) but no performance differences from controls on colour congruent (e.g. "RED" printed in red ink) or neutral trials (e.g. "*****" printed in green ink). Poorer incongruent trial performance was predicted by an earlier age of onset of regular cannabis use. Users showed altered expression of a late sustained potential related to conflict resolution, evident by opposite patterns of activity between trial types at midline and central sites, and altered relationships between neurophysiological and behavioural outcome measures not evident in the control group. These findings indicate that chronic use of cannabis may impair the brain's ability to respond optimally in the presence of events that require conflict resolution and hold implications for the ability to refrain from substance misuse and/or maintain substance abstention behaviours.

  17. Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality.

    Science.gov (United States)

    Metzger, Michael W; Walser, Sandra M; Dedic, Nina; Aprile-Garcia, Fernando; Jakubcakova, Vladimira; Adamczyk, Marek; Webb, Katharine J; Uhr, Manfred; Refojo, Damian; Schmidt, Mathias V; Friess, Elisabeth; Steiger, Axel; Kimura, Mayumi; Chen, Alon; Holsboer, Florian; Arzt, Eduardo; Wurst, Wolfgang; Deussing, Jan M

    2017-11-29

    A single nucleotide polymorphism substitution from glutamine (Gln, Q) to arginine (Arg, R) at codon 460 of the purinergic P2X7 receptor (P2X7R) has repeatedly been associated with mood disorders. The P2X7R-Gln460Arg variant per se is not compromised in its function. However, heterologous expression of P2X7R-Gln460Arg together with wild-type P2X7R has recently been demonstrated to impair receptor function. Here we show that this also applies to humanized mice coexpressing both human P2X7R variants. Primary hippocampal cells derived from heterozygous mice showed an attenuated calcium uptake upon agonist stimulation. While humanized mice were unaffected in their behavioral repertoire under basal housing conditions, mice that harbor both P2X7R variants showed alterations in their sleep quality resembling signs of a prodromal disease stage. Also healthy heterozygous human subjects showed mild changes in sleep parameters. These results indicate that heterozygosity for the wild-type P2X7R and its mood disorder-associated variant P2X7R-Gln460Arg represents a genetic risk factor, which is potentially able to convey susceptibility to mood disorders. SIGNIFICANCE STATEMENT Depression and bipolar disorder are the most common mood disorders. The P2X7 receptor (P2X7R) regulates many cellular functions. Its polymorphic variant Gln460Arg has repeatedly been associated with mood disorders. Genetically engineered mice, with human P2X7R, revealed that heterozygous mice (i.e., they coexpress the disease-associated Gln460Arg variant together with its normal version) have impaired receptor function and showed sleep disturbances. Human participants with the heterozygote genotype also had subtle alterations in their sleep profile. Our findings suggest that altered P2X7R function in heterozygote individuals disturbs sleep and might increase the risk for developing mood disorders. Copyright © 2017 the authors 0270-6474/17/3711688-13$15.00/0.

  18. Alterations in Normal Aging Revealed by Cortical Brain Network Constructed Using IBASPM.

    Science.gov (United States)

    Li, Wan; Yang, Chunlan; Shi, Feng; Wang, Qun; Wu, Shuicai; Lu, Wangsheng; Li, Shaowu; Nie, Yingnan; Zhang, Xin

    2018-04-16

    Normal aging has been linked with the decline of cognitive functions, such as memory and executive skills. One of the prominent approaches to investigate the age-related alterations in the brain is by examining the cortical brain connectome. IBASPM is a toolkit to realize individual atlas-based volume measurement. Hence, this study seeks to determine what further alterations can be revealed by cortical brain networks formed by IBASPM-extracted regional gray matter volumes. We found the reduced strength of connections between the superior temporal pole and middle temporal pole in the right hemisphere, global hubs as the left fusiform gyrus and right Rolandic operculum in the young and aging groups, respectively, and significantly reduced inter-module connection of one module in the aging group. These new findings are consistent with the phenomenon of normal aging mentioned in previous studies and suggest that brain network built with the IBASPM could provide supplementary information to some extent. The individualization of morphometric features extraction deserved to be given more attention in future cortical brain network research.

  19. Environmental exposure and altered menstrual function

    Energy Technology Data Exchange (ETDEWEB)

    Keye, W.R. Jr.

    1984-01-01

    The impact of environmental agents and occupational factors on hypothalamic and pituitary function and menstruation are poorly understood. To date, most research related to environment, occupation, and reproduction has focused on pregnancy outcome, not menstrual function. It is imperative, however, that menstrual function be considered as an outcome variable in the study of reproduction and occupation.

  20. [Aberrant topological properties of whole-brain functional network in chronic right-sided sensorineural hearing loss: a resting-state functional MRI study].

    Science.gov (United States)

    Zhang, Lingling; Liu, Bin; Xu, Yangwen; Yang, Ming; Feng, Yuan; Huang, Yaqing; Huan, Zhichun; Hou, Zhaorui

    2015-02-03

    To investigate the topological properties of the functional brain network in unilateral sensorineural hearing loss patients. In this study, we acquired resting-state BOLD- fMRI data from 19 right-sided SNHL patients and 31 healthy controls with normal hearing and constructed their whole brain functional networks. Two-sample two-tailed t-tests were performed to investigate group differences in topological parameters between the USNHL patients and the controls. Partial correlation analysis was conducted to determine the relationships between the network metrics and USNHL-related variables. Both USNHL patients and controls exhibited small-word architecture in their brain functional networks within the range 0. 1 - 0. 2 of sparsity. Compared to the controls, USNHL patients showed significant increase in characteristic path length and normalized characteristic path length, but significant decrease in global efficiency. Clustering coefficient, local efficiency and normalized clustering coefficient demonstrated no significant difference. Furthermore, USNHL patients exhibited no significant association between the altered network metrics and the duration of USNHL or the severity of hearing loss. Our results indicated the altered topological properties of whole brain functional networks in USNHL patients, which may help us to understand pathophysiologic mechanism of USNHL patients.

  1. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    Energy Technology Data Exchange (ETDEWEB)

    Blossom, Sarah J., E-mail: blossomsarah@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, College of Medicine, Arkansas Children' s Hospital Research Institute, 13 Children' s Way, Little Rock, AR 72202 (United States); Cooney, Craig A. [Department of Research and Development, Central Arkansas Veterans Healthcare System, John L. McClellan Memorial Veterans Hospital, 4300 West 7th St., Little Rock, AR 72205-5484 (United States); Melnyk, Stepan B.; Rau, Jenny L.; Swearingen, Christopher J. [Department of Pediatrics, University of Arkansas for Medical Sciences, College of Medicine, Arkansas Children' s Hospital Research Institute, 13 Children' s Way, Little Rock, AR 72202 (United States); Wessinger, William D. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, College of Medicine, 4301 West Markham St., Little Rock, AR 72205 (United States)

    2013-06-15

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL +/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. - Highlights: • We exposed male mice to low-level trichloroethylene from postnatal days 1 through 42. • This exposure altered redox potential and increased oxidative stress in cerebellum. • This exposure altered metabolites important in cellular methylation in cerebellum. • This exposure promoted DNA hypomethylation in cerebellum. • This exposure enhanced locomotor

  2. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    International Nuclear Information System (INIS)

    Blossom, Sarah J.; Cooney, Craig A.; Melnyk, Stepan B.; Rau, Jenny L.; Swearingen, Christopher J.; Wessinger, William D.

    2013-01-01

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL +/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. - Highlights: • We exposed male mice to low-level trichloroethylene from postnatal days 1 through 42. • This exposure altered redox potential and increased oxidative stress in cerebellum. • This exposure altered metabolites important in cellular methylation in cerebellum. • This exposure promoted DNA hypomethylation in cerebellum. • This exposure enhanced locomotor

  3. Altered Function and Expression of ABC Transporters at the Blood–Brain Barrier and Increased Brain Distribution of Phenobarbital in Acute Liver Failure Mice

    Directory of Open Access Journals (Sweden)

    Li Liu

    2018-03-01

    Full Text Available This study investigated alterations in the function and expression of P-glycoprotein (P-GP, breast cancer resistance protein (BCRP, and multidrug resistance-associated protein 2 (MRP2 at the blood–brain barrier (BBB of acute liver failure (ALF mice and its clinical significance. ALF mice were developed using intraperitoneal injection of thioacetamide. P-GP, BCRP, and MRP2 functions were determined by measuring the ratios of brain-to-plasma concentration of rhodamine 123, prazosin, and dinitrophenyl-S-glutathione, respectively. The mRNA and proteins expression levels of P-GP, BCRP, and MRP2 were evaluated with quantitative real-time PCR and western blot, respectively. MDCK-MDR1 and HCMEC/D3 cells were used to document the effects of the abnormally altered components in serum of ALF mice on the function and expression of P-GP. The clinical significance of alteration in P-GP function and expression was investigated by determining the distribution of the P-GP substrate phenobarbital (60 mg/kg, intravenous administration in the brain and loss of righting reflex (LORR induced by the drug (100 mg/kg. The results showed that ALF significantly downregulated the function and expression of both P-GP and BCRP, but increased the function and expression of MRP2 in the brain of mice. Cell study showed that increased chenodeoxycholic acid may be a reason behind the downregulated P-GP function and expression. Compared with control mice, ALF mice showed a significantly higher brain concentration of phenobarbital and higher brain-to-plasma concentration ratios. In accordance, ALF mice showed a significantly larger duration of LORR and shorter latency time of LORR by phenobarbital, inferring the enhanced pharmacological effect of phenobarbital on the central nervous system (CNS. In conclusion, the function and expression of P-GP and BCRP decreased, while the function and expression of MRP2 increased in the brain of ALF mice. The attenuated function and expression

  4. Global meta-analysis of leaf area index in wetlands indicates uncertainties in understanding of their ecosystem function

    Science.gov (United States)

    Dronova, I.; Taddeo, S.; Foster, K.

    2017-12-01

    Projecting ecosystem responses to global change relies on the accurate understanding of properties governing their functions in different environments. An important variable in models of ecosystem function is canopy leaf area index (LAI; leaf area per unit ground area) declared as one of the Essential Climate Variables in the Global Climate Observing System and extensively measured in terrestrial landscapes. However, wetlands have been largely under-represented in these efforts, which globally limits understanding of their contribution to carbon sequestration, climate regulation and resilience to natural and anthropogenic disturbances. This study provides a global synthesis of >350 wetland-specific LAI observations from 182 studies and compares LAI among wetland ecosystem and vegetation types, biomes and measurement approaches. Results indicate that most wetland types and even individual locations show a substantial local dispersion of LAI values (average coefficient of variation 65%) due to heterogeneity of environmental properties and vegetation composition. Such variation indicates that mean LAI values may not sufficiently represent complex wetland environments, and the use of this index in ecosystem function models needs to incorporate within-site variation in canopy properties. Mean LAI did not significantly differ between direct and indirect measurement methods on a pooled global sample; however, within some of the specific biomes and wetland types significant contrasts between these approaches were detected. These contrasts highlight unique aspects of wetland vegetation physiology and canopy structure affecting measurement principles that need to be considered in generalizing canopy properties in ecosystem models. Finally, efforts to assess wetland LAI using remote sensing strongly indicate the promise of this technology for cost-effective regional-scale modeling of canopy properties similar to terrestrial systems. However, such efforts urgently require more

  5. Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study.

    Science.gov (United States)

    van Veenendaal, Tamar M; IJff, Dominique M; Aldenkamp, Albert P; Lazeron, Richard H C; Hofman, Paul A M; de Louw, Anton J A; Backes, Walter H; Jansen, Jacobus F A

    2017-06-28

    To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment. The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category (lamotrigine or levetiracetam, n = 16), an "intermediate risk" category (carbamazepine, oxcarbazepine, phenytoin, or valproate, n = 34) and a "high risk" category (topiramate, n = 5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment. Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant ( P effect on the clustering coefficient (ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient (linear regression analysis, P > 0.15) were observed. Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.

  6. Multi-ethnic reference values for spirometry for the 3-95-yr age range: The global lung function 2012 equations

    NARCIS (Netherlands)

    P.H. Quanjer (Philip); S. Stanojevic (Sanja); T.J. Cole (Tim); X. Baur (Xaver); G.L. Hall (G. L.); B.H. Culver (Bruce); P.L. Enright (Paul); J.L. Hankinson; M.S.M. Ip; J. Zheng (Jinping); J. Stocks (Janet); C. Schindler (C.)

    2012-01-01

    textabstractThe aim of the Task Force was to derive continuous prediction equations and their lower limits of normal for spirometric indices, which are applicable globally. Over 160,000 data points from 72 centres in 33 countries were shared with the European Respiratory Society Global Lung Function

  7. Altered brain network topology in left-behind children: A resting-state functional magnetic resonance imaging study.

    Science.gov (United States)

    Zhao, Youjin; Du, Meimei; Gao, Xin; Xiao, Yuan; Shah, Chandan; Sun, Huaiqiang; Chen, Fuqin; Yang, Lili; Yan, Zhihan; Fu, Yuchuan; Lui, Su

    2016-12-01

    Whether a lack of direct parental care affects brain function in children is an important question, particularly in developing countries where hundreds of millions of children are left behind when their parents migrate for economic or political reasons. In this study, we investigated changes in the topological architectures of brain functional networks in left-behind children (LBC). Resting-state functional magnetic resonance imaging data were obtained from 26 LBC and 21 children living within their nuclear family (non-LBC). LBC showed a significant increase in the normalized characteristic path length (λ), suggesting a decrease in efficiency in information access, and altered nodal centralities in the fronto-limbic regions and motor and sensory systems. Moreover, a decreased nodal degree and the nodal betweenness of the right rectus gyrus were positively correlated with annual family income. The present study provides the first empirical evidence that suggests that a lack of direct parental care could affect brain functional development in children, particularly involving emotional networks. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

    Science.gov (United States)

    Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

    2017-07-04

    This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

  9. Interaction of a common painkiller piroxicam and copper-piroxicam with chromatin causes structural alterations accompanied by modulation at the epigenomic/genomic level.

    Science.gov (United States)

    Goswami, Sathi; Sanyal, Sulagna; Chakraborty, Payal; Das, Chandrima; Sarkar, Munna

    2017-08-01

    NSAIDs are the most common class of painkillers and anti-inflammatory agents. They also show other functions like chemoprevention and chemosuppression for which they act at the protein but not at the genome level since they are mostly anions at physiological pH, which prohibit their approach to the poly-anionic DNA. Complexing the drugs with bioactive metal obliterate their negative charge and allow them to bind to the DNA, thereby, opening the possibility of genome level interaction. To test this hypothesis, we present the interaction of a traditional NSAID, Piroxicam and its copper complex with core histone and chromatin. Spectroscopy, DLS, and SEM studies were applied to see the effect of the interaction on the structure of histone/chromatin. This was coupled with MTT assay, immunoblot analysis, confocal microscopy, micro array analysis and qRT-PCR. The interaction of Piroxicam and its copper complex with histone/chromatin results in structural alterations. Such structural alterations can have different biological manifestations, but to test our hypothesis, we have focused only on the accompanied modulations at the epigenomic/genomic level. The complex, showed alteration of key epigenetic signatures implicated in transcription in the global context, although Piroxicam caused no significant changes. We have correlated such alterations caused by the complex with the changes in global gene expression and validated the candidate gene expression alterations. Our results provide the proof of concept that DNA binding ability of the copper complexes of a traditional NSAID, opens up the possibility of modulations at the epigenomic/genomic level. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Impact of global climate change and fire on the occurrence and function of understorey legumes in forest ecosystems

    Energy Technology Data Exchange (ETDEWEB)

    Reverchon, Frederique; Xu, Zhihong; Blumfield, Timothy J.; Chen, Chengrong; Abdullah, Kadum M. [Griffith Univ., Nathan, QLD (Australia). Environmental Futures Centre and School of Biomolecular and Physical Sciences

    2012-02-15

    The objective of this review was to provide a better understanding of how global climate change and fire influence the occurrence of understorey legumes and thereby biological nitrogen (N) fixation rates in forest ecosystems. Legumes are interesting models since they represent an interface between the soil, plant, and microbial compartments, and are directly linked to nutrient cycles through their ability to fix N. As such, they are likely to be affected by environmental changes. Biological N fixation has been shown to increase under enriched CO{sub 2} conditions, but is constrained by the availability of phosphorus and water. Climate change can also influence the species composition of legumes and their symbionts through warming, altered rainfall patterns, or changes in soil physicochemistry, which could modify the effectiveness of the symbiosis. Additionally, global climate change may increase the occurrence and intensity of forest wildfires thereby further influencing the distribution of legumes. The establishment of leguminous species is generally favored by fire, as is N{sub 2} fixation. This fixed N could therefore replenish the N lost through volatilization during the fire. However, fire may also generate shifts in the associated microbial community which could affect the outcome of the symbiosis. Understorey legumes are important functional species, and even when they cannot reasonably be expected to reestablish the nutrient balance in forest soils, they may be used as indicators to monitor nutrient fluxes and the response of forest ecosystems to changing environmental conditions. This would be helpful to accurately model ecosystem N budgets, and since N is often a limiting factor to plant growth and a major constraint on C storage in ecosystems, would allow us to assess more precisely the potential of these forests for C sequestration. (orig.)

  11. Calculation of probability density functions for temperature and precipitation change under global warming

    International Nuclear Information System (INIS)

    Watterson, Ian G.

    2007-01-01

    Full text: he IPCC Fourth Assessment Report (Meehl ef al. 2007) presents multi-model means of the CMIP3 simulations as projections of the global climate change over the 21st century under several SRES emission scenarios. To assess the possible range of change for Australia based on the CMIP3 ensemble, we can follow Whetton etal. (2005) and use the 'pattern scaling' approach, which separates the uncertainty in the global mean warming from that in the local change per degree of warming. This study presents several ways of representing these two factors as probability density functions (PDFs). The beta distribution, a smooth, bounded, function allowing skewness, is found to provide a useful representation of the range of CMIP3 results. A weighting of models based on their skill in simulating seasonal means in the present climate over Australia is included. Dessai ef al. (2005) and others have used Monte-Carlo sampling to recombine such global warming and scaled change factors into values of net change. Here, we use a direct integration of the product across the joint probability space defined by the two PDFs. The result is a cumulative distribution function (CDF) for change, for each variable, location, and season. The median of this distribution provides a best estimate of change, while the 10th and 90th percentiles represent a likely range. The probability of exceeding a specified threshold can also be extracted from the CDF. The presentation focuses on changes in Australian temperature and precipitation at 2070 under the A1B scenario. However, the assumption of linearity behind pattern scaling allows results for different scenarios and times to be simply obtained. In the case of precipitation, which must remain non-negative, a simple modification of the calculations (based on decreases being exponential with warming) is used to avoid unrealistic results. These approaches are currently being used for the new CSIRO/ Bureau of Meteorology climate projections

  12. Global marine plankton functional type biomass distributions : Phaeocystis spp

    NARCIS (Netherlands)

    Vogt, M.; O'Brien, C.; Peloquin, J.; Schoemann, V.; Breton, E.; Estrada, M.; Gibson, J.; Karentz, D.; van Leeuwe, M. A.; Stefels, J.; Widdicombe, C.; Peperzak, L.

    2012-01-01

    The planktonic haptophyte Phaeocystis has been suggested to play a fundamental role in the global biogeochemical cycling of carbon and sulphur, but little is known about its global biomass distribution. We have collected global microscopy data of the genus Phaeocystis and converted abundance data to

  13. Reduced loss aversion in pathological gambling and alcohol dependence is associated with differential alterations in amygdala and prefrontal functioning.

    Science.gov (United States)

    Genauck, Alexander; Quester, Saskia; Wüstenberg, Torsten; Mörsen, Chantal; Heinz, Andreas; Romanczuk-Seiferth, Nina

    2017-11-24

    Diagnostic criteria for pathological gambling and alcohol dependence (AD) include repeated addictive behavior despite severe negative consequences. However, the concept of loss aversion (LA) as a facet of value-based decision making has not yet been used to directly compare these disorders. We hypothesized reduced LA in pathological gamblers (PG) and AD patients, correlation of LA with disorder severity, and reduced loss-related modulation of brain activity. 19 PG subjects, 15 AD patients and 17 healthy controls (HC) engaged in a LA task in a functional magnetic resonance imaging setting. Imaging analyses focused on neural gain and loss sensitivity in the meso-cortico-limbic network of the brain. Both PG and AD subjects showed reduced LA. AD subjects showed altered loss-related modulation of activity in lateral prefrontal regions. PG subjects showed indication of altered amygdala-prefrontal functional connectivity. Although we observed reduced LA in both a behavioral addiction and a substance-related disorder our neural findings might challenge the notion of complete neuro-behavioral congruence of substance-use disorders and behavioral addictions.

  14. Role of dopaminergic and serotonergic neurotransmitters in behavioral alterations observed in rodent model of hepatic encephalopathy.

    Science.gov (United States)

    Dhanda, Saurabh; Sandhir, Rajat

    2015-06-01

    The present study was designed to evaluate the role of biogenic amines in behavioral alterations observed in rat model of hepatic encephalopathy (HE) following bile duct ligation (BDL). Male Wistar rats subjected to BDL developed biliary fibrosis after four weeks which was supported by altered liver function tests, increased ammonia levels and histological staining (Sirius red). Animals were assessed for their behavioral performance in terms of cognitive, anxiety and motor functions. The levels of dopamine (DA), serotonin (5-HT), epinephrine and norepinephrine (NE) were estimated in different regions of brain viz. cortex, hippocampus, striatum and cerebellum using HPLC along with activity of monoamine oxidase (MAO). Cognitive assessment of BDL rats revealed a progressive decline in learning, memory formation, retrieval, exploration of novel environment and spontaneous locomotor activity along with decrease in 5-HT and NE levels. This was accompanied by an increase in MAO activity. Motor functions of BDL rats were also altered which were evident from decrease in the time spent on the rotating rod and higher foot faults assessed using narrow beam walk task. A global decrease was observed in the DA content along with an increase in MAO activity. Histopathological studies using hematoxylin-eosin (H&E) and cresyl violet exhibited marked neuronal degeneration, wherein neurons appeared more pyknotic, condensed and damaged. The results reveal that dopaminergic and serotonergic pathways are disturbed in chronic liver failure post-BDL which may be responsible for behavioral impairments observed in HE. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The Risk Management Functions in the Conditions of Globalization: Case Study of the Republic of Serbia

    Directory of Open Access Journals (Sweden)

    Zlatija Jelenković

    2016-09-01

    Full Text Available Globalization, which represents an important transmission mechanism of the crisis, has led to the necessity for controlling various risks of business, setting a new line of management in companies, regardless of the main business activity they are engaged in. The economic crisis in general, and especially the global financial crises (2007 and the present one led to bankruptcy, and thus to loss of funds of many businesses and individuals. Therefore, it was necessary, on the one hand, to ensure confidence in the financial system and to maintain its stability. On the other hand, the development of corporate governance and separation of functions of ownership and management insisted on the creation of functions that directly report to the owners of capital, such as risk management and internal audit. The value of this paper is in emphasizing the new management function and raising awareness of the scientific public and businesses about the need for introduction of risk management functions in order to facilitate effective management of enterprises, although the survey (2012-2015 has shown that the existence of legal obligations, in this regard penal policy, is the only thing that effectively establishes and promotes this area.

  16. Species replacement by a nonnative salmonid alters ecosystem function by reducing prey subsidies that support riparian spiders

    Science.gov (United States)

    Benjamin, J.R.; Fausch, K.D.; Baxter, C.V.

    2011-01-01

    Replacement of a native species by a nonnative can have strong effects on ecosystem function, such as altering nutrient cycling or disturbance frequency. Replacements may cause shifts in ecosystem function because nonnatives establish at different biomass, or because they differ from native species in traits like foraging behavior. However, no studies have compared effects of wholesale replacement of a native by a nonnative species on subsidies that support consumers in adjacent habitats, nor quantified the magnitude of these effects. We examined whether streams invaded by nonnative brook trout (Salvelinus fontinalis) in two regions of the Rocky Mountains, USA, produced fewer emerging adult aquatic insects compared to paired streams with native cutthroat trout (Oncorhynchus clarkii), and whether riparian spiders that depend on these prey were less abundant along streams with lower total insect emergence. As predicted, emergence density was 36% lower from streams with the nonnative fish. Biomass of brook trout was higher than the cutthroat trout they replaced, but even after accounting for this difference, emergence was 24% lower from brook trout streams. More riparian spiders were counted along streams with greater total emergence across the water surface. Based on these results, we predicted that brook trout replacement would result in 6-20% fewer spiders in the two regions. When brook trout replace cutthroat trout, they reduce cross-habitat resource subsidies and alter ecosystem function in stream-riparian food webs, not only owing to increased biomass but also because traits apparently differ from native cutthroat trout. ?? 2011 Springer-Verlag.

  17. Global change impacts on mangrove ecosystems

    Science.gov (United States)

    McKee, Karen L.

    2004-01-01

    Mangroves are tropical/subtropical communities of primarily tree species that grow in the intertidal zone. These tidal forests are important coastal ecosystems that are valued for a variety of ecological and societal goods and services. Major local threats to mangrove ecosystems worldwide include clearcutting and trimming of forests for urban, agricultural, or industrial expansion; hydrological alterations; toxic chemical spills; and eutrophication. In many countries with mangroves, much of the human population resides in the coastal zone, and their activities often negatively impact the integrity of mangrove forests. In addition, eutrophication, which is the process whereby nutrients build up to higher than normal levels in a natural system, is possibly one of the most serious threats to mangroves and associated ecosystems such as coral reefs. Scientists with the U.S. Geological Survey (USGS) at the National Wetlands Research Center are working to more fully understand global impacts on these significant ecosystems.Changes in climate and other factors may also affect mangroves, but in complex ways. Global warming may promote expansion of mangrove forests to higher latitudes and accelerate sea-level rise through melting of polar ice or steric expansion of oceans. Changes in sea level would alter flooding patterns and the structure and areal extent of mangroves. Climate change may also alter rainfall patterns, which would in turn change local salinity regimes and competitive interactions of mangroves with other wetland species. Increases in frequency or intensity of tropical storms and hurricanes in combination with sea-level rise may alter erosion and sedimentation rates in mangrove forests. Another global change factor that may directly affect mangrove growth is increased atmospheric carbon dioxide (CO2), caused by burning of fossil fuels and other factors. Elevated CO2 concentration may increase mangrove growth by stimulating photosynthesis or improving water use

  18. Disrupted functional connectome in antisocial personality disorder.

    Science.gov (United States)

    Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen; Wang, Wei; Shen, Dinggang

    2017-08-01

    Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD.

  19. Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice

    International Nuclear Information System (INIS)

    Urióstegui-Acosta, Mayrut; Hernández-Ochoa, Isabel; Sánchez-Gutiérrez, Manuel; Piña-Guzmán, Belem; Rafael-Vázquez, Leticia; Solís-Heredia, M.J.; Martínez-Aguilar, Gerardo; Quintanilla-Vega, Betzabet

    2014-01-01

    Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5 mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis–vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43–57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5 mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5 mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5 mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation. - Highlights: • Methamidophos alters sperm cell function at different stages of spermatogenesis. • Testicular stages of spermatogenesis are more sensitive to

  20. Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Urióstegui-Acosta, Mayrut; Hernández-Ochoa, Isabel [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico); Sánchez-Gutiérrez, Manuel [Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Hidalgo (Mexico); Piña-Guzmán, Belem [Instituto Politécnico Nacional-UPIBI, D.F. (Mexico); Rafael-Vázquez, Leticia; Solís-Heredia, M.J.; Martínez-Aguilar, Gerardo [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico); Quintanilla-Vega, Betzabet, E-mail: mquintan@cinvestav.mx [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico)

    2014-09-15

    Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5 mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis–vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43–57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5 mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5 mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5 mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation. - Highlights: • Methamidophos alters sperm cell function at different stages of spermatogenesis. • Testicular stages of spermatogenesis are more sensitive to

  1. Altered Mycobacterium tuberculosis Cell Wall Metabolism and Physiology Associated With RpoB Mutation H526D

    Directory of Open Access Journals (Sweden)

    Victoria L. Campodónico

    2018-03-01

    Full Text Available Background:Mycobacterium tuberculosis (Mtb rpoB mutations are associated with global metabolic remodeling. However, the net effects of rpoB mutations on Mtb physiology, metabolism and function are not completely understood. Based on previous work, we hypothesized that changes in the expression of cell wall molecules in Mtb mutant RpoB 526D lead to changes in cell wall permeability and to altered resistance to environmental stresses and drugs.Methods: The phenotypes of a fully drug-susceptible clinical strain of Mtb and its paired rifampin-monoresistant, RpoB H526D mutant progeny strain were compared.Results: The rpoB mutant showed altered colony morphology, bacillary length and cell wall thickness, which were associated with increased cell wall permeability and susceptibility to the cell wall detergent sodium dodecyl sulfate (SDS after exposure to nutrient starvation. Relative to the isogenic rifampin-susceptible strain, the RpoB H526D mutant showed altered bacterial cellular metabolic activity and an eightfold increase in susceptibility to the cell-wall acting drug vancomycin.Conclusion: Our data suggest that RpoB mutation H526D is associated with altered cell wall physiology and resistance to cell wall-related stress. These findings are expected to contribute to an improved understanding of the pathogenesis of drug-resistant M. tuberculosis infections.

  2. Altered default network resting-state functional connectivity in adolescents with Internet gaming addiction.

    Science.gov (United States)

    Ding, Wei-na; Sun, Jin-hua; Sun, Ya-wen; Zhou, Yan; Li, Lei; Xu, Jian-rong; Du, Ya-song

    2013-01-01

    Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA). Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC) connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS) and Barratt Impulsiveness Scale-11 (BIS-11) and their hours of Internet use per week. There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours) (paddiction, they support the hypothesis that IGA as a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders.

  3. General, crystallized and fluid intelligence are not associated with functional global network efficiency: A replication study with the human connectome project 1200 data set.

    Science.gov (United States)

    Kruschwitz, J D; Waller, L; Daedelow, L S; Walter, H; Veer, I M

    2018-05-01

    One hallmark example of a link between global topological network properties of complex functional brain connectivity and cognitive performance is the finding that general intelligence may depend on the efficiency of the brain's intrinsic functional network architecture. However, although this association has been featured prominently over the course of the last decade, the empirical basis for this broad association of general intelligence and global functional network efficiency is quite limited. In the current study, we set out to replicate the previously reported association between general intelligence and global functional network efficiency using the large sample size and high quality data of the Human Connectome Project, and extended the original study by testing for separate association of crystallized and fluid intelligence with global efficiency, characteristic path length, and global clustering coefficient. We were unable to provide evidence for the proposed association between general intelligence and functional brain network efficiency, as was demonstrated by van den Heuvel et al. (2009), or for any other association with the global network measures employed. More specifically, across multiple network definition schemes, ranging from voxel-level networks to networks of only 100 nodes, no robust associations and only very weak non-significant effects with a maximal R 2 of 0.01 could be observed. Notably, the strongest (non-significant) effects were observed in voxel-level networks. We discuss the possibility that the low power of previous studies and publication bias may have led to false positive results fostering the widely accepted notion of general intelligence being associated to functional global network efficiency. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. White matter alterations and their associations with motor function in young adults born preterm with very low birth weight

    Directory of Open Access Journals (Sweden)

    Ingrid Marie Husby Hollund

    2018-01-01

    Full Text Available Very low birth weight (VLBW: ≤1500 g individuals have an increased risk of white matter alterations and neurodevelopmental problems, including fine and gross motor problems. In this hospital-based follow-up study, the main aim was to examine white matter microstructure and its relationship to fine and gross motor function in 31 VLBW young adults without cerebral palsy compared with 31 term-born controls, at mean age 22.6 ± 0.7 years. The participants were examined with tests of fine and gross motor function (Trail Making Test-5: TMT-5, Grooved Pegboard, Triangle from Movement Assessment Battery for Children-2: MABC-2 and High-level Mobility Assessment Tool: HiMAT and diffusion tensor imaging (DTI. Probabilistic tractography of motor pathways of the corticospinal tract (CST and corpus callosum (CC was performed. Fractional anisotropy (FA was calculated in non-crossing (capsula interna in CST, body of CC and crossing (centrum semiovale fibre regions along the tracts and examined for group differences. Associations between motor test scores and FA in the CST and CC were investigated with linear regression. Tract-based spatial statistics (TBSS was used to examine group differences in DTI metrics in all major white matter tracts. The VLBW group had lower scores on all motor tests compared with controls, however, only statistically significant for TMT-5. Based on tractography, FA in the VLBW group was lower in non-crossing fibre regions and higher in crossing fibre regions of the CST compared with controls. Within the VLBW group, poorer fine motor function was associated with higher FA in crossing fibre regions of the CST, and poorer bimanual coordination was additionally associated with lower FA in crossing fibre regions of the CC. Poorer gross motor function was associated with lower FA in crossing fibre regions of the CST and CC. There were no associations between motor function and FA in non-crossing fibre regions of the CST and CC within

  5. White matter alterations and their associations with motor function in young adults born preterm with very low birth weight.

    Science.gov (United States)

    Hollund, Ingrid Marie Husby; Olsen, Alexander; Skranes, Jon; Brubakk, Ann-Mari; Håberg, Asta K; Eikenes, Live; Evensen, Kari Anne I

    2018-01-01

    Very low birth weight (VLBW: ≤ 1500 g) individuals have an increased risk of white matter alterations and neurodevelopmental problems, including fine and gross motor problems. In this hospital-based follow-up study, the main aim was to examine white matter microstructure and its relationship to fine and gross motor function in 31 VLBW young adults without cerebral palsy compared with 31 term-born controls, at mean age 22.6 ± 0.7 years. The participants were examined with tests of fine and gross motor function (Trail Making Test-5: TMT-5, Grooved Pegboard, Triangle from Movement Assessment Battery for Children-2: MABC-2 and High-level Mobility Assessment Tool: HiMAT) and diffusion tensor imaging (DTI). Probabilistic tractography of motor pathways of the corticospinal tract (CST) and corpus callosum (CC) was performed. Fractional anisotropy (FA) was calculated in non-crossing (capsula interna in CST, body of CC) and crossing (centrum semiovale) fibre regions along the tracts and examined for group differences. Associations between motor test scores and FA in the CST and CC were investigated with linear regression. Tract-based spatial statistics (TBSS) was used to examine group differences in DTI metrics in all major white matter tracts. The VLBW group had lower scores on all motor tests compared with controls, however, only statistically significant for TMT-5. Based on tractography, FA in the VLBW group was lower in non-crossing fibre regions and higher in crossing fibre regions of the CST compared with controls. Within the VLBW group, poorer fine motor function was associated with higher FA in crossing fibre regions of the CST, and poorer bimanual coordination was additionally associated with lower FA in crossing fibre regions of the CC. Poorer gross motor function was associated with lower FA in crossing fibre regions of the CST and CC. There were no associations between motor function and FA in non-crossing fibre regions of the CST and CC within the VLBW

  6. Alterations of global histone H4K20 methylation during prostate carcinogenesis

    Directory of Open Access Journals (Sweden)

    Behbahani Turang E

    2012-03-01

    Full Text Available Abstract Background Global histone modifications have been implicated in the progression of various tumour entities. Our study was designed to assess global methylation levels of histone 4 lysine 20 (H4K20me1-3 at different stages of prostate cancer (PCA carcinogenesis. Methods Global H4K20 methylation levels were evaluated using a tissue microarray in patients with clinically localized PCA (n = 113, non-malignant prostate disease (n = 27, metastatic hormone-naive PCA (mPCA, n = 30 and castration-resistant PCA (CRPC, n = 34. Immunohistochemistry was performed to assess global levels of H4K20 methylation levels. Results Similar proportions of the normal, PCA, and mPCA prostate tissues showed strong H4K20me3 staining. CRPC tissue analysis showed the weakest immunostaining levels of H4K20me1 and H4K20me2, compared to other prostate tissues. H4K20me2 methylation levels indicated significant differences in examined tissues except for normal prostate versus PCA tissue. H4K20me1 differentiates CRPC from other prostate tissues. H4K20me1 was significantly correlated with lymph node metastases, and H4K20me2 showed a significant correlation with the Gleason score. However, H4K20 methylation levels failed to predict PSA recurrence after radical prostatectomy. Conclusions H4K20 methylation levels constitute valuable markers for the dynamic process of prostate cancer carcinogenesis.

  7. Soil bacterial community and functional shifts in response to altered snowpack in moist acidic tundra of northern Alaska

    Science.gov (United States)

    Ricketts, Michael P.; Poretsky, Rachel S.; Welker, Jeffrey M.; Gonzalez-Meler, Miquel A.

    2016-09-01

    Soil microbial communities play a central role in the cycling of carbon (C) in Arctic tundra ecosystems, which contain a large portion of the global C pool. Climate change predictions for Arctic regions include increased temperature and precipitation (i.e. more snow), resulting in increased winter soil insulation, increased soil temperature and moisture, and shifting plant community composition. We utilized an 18-year snow fence study site designed to examine the effects of increased winter precipitation on Arctic tundra soil bacterial communities within the context of expected ecosystem response to climate change. Soil was collected from three pre-established treatment zones representing varying degrees of snow accumulation, where deep snow ˜ 100 % and intermediate snow ˜ 50 % increased snowpack relative to the control, and low snow ˜ 25 % decreased snowpack relative to the control. Soil physical properties (temperature, moisture, active layer thaw depth) were measured, and samples were analysed for C concentration, nitrogen (N) concentration, and pH. Soil microbial community DNA was extracted and the 16S rRNA gene was sequenced to reveal phylogenetic community differences between samples and determine how soil bacterial communities might respond (structurally and functionally) to changes in winter precipitation and soil chemistry. We analysed relative abundance changes of the six most abundant phyla (ranging from 82 to 96 % of total detected phyla per sample) and found four (Acidobacteria, Actinobacteria, Verrucomicrobia, and Chloroflexi) responded to deepened snow. All six phyla correlated with at least one of the soil chemical properties (% C, % N, C : N, pH); however, a single predictor was not identified, suggesting that each bacterial phylum responds differently to soil characteristics. Overall, bacterial community structure (beta diversity) was found to be associated with snow accumulation treatment and all soil chemical properties. Bacterial

  8. Morphologic and functional alterations induced by low doses of mercuric chloride in the kidney OK cell line: ultrastructural evidence for an apoptotic mechanism of damage

    International Nuclear Information System (INIS)

    Carranza-Rosales, Pilar; Said-Fernandez, Salvador; Sepulveda-Saavedra, Julio; Cruz-Vega, Delia E.; Gandolfi, A. Jay

    2005-01-01

    Mercury produces acute renal failure in experimental animal models, but the mechanism of tubular injury has not completely been clarified. There is an increased interest in the role of apoptosis in the pathogenesis of renal diseases that result primarily from injury to renal tubular epithelial cells. However, detailed studies of morpho-functional alterations induced by mercuric chloride in kidney cell lines are scarce. This work characterizes these alterations in OK cell cultures. Morphological alterations were profiled using light microscopy, transmission electron microscopy, and confocal microscopy, as well as mitochondrial functional assays in the cells exposed to low concentrations of HgCl 2 . At concentrations of 1 and 10 μM of HgCl 2 there were no morphological or ultrastructural alterations, but the mitochondrial function (MTT assay) and intracellular ATP content was increased, especially at longer incubation times (6 and 9 h). At 15 μM HgCl 2 , both the mitochondrial activity and the endogenous ATP decreased significantly. At this concentration the OK cells rounded up, had increased number of cytoplasmic vacuoles, and detached from the cell monolayer. At 15 μM HgCl 2 ultrastructural changes were characterized by dispersion of the ribosomes, dilatation of the cisterns of the rough endoplasmic reticulum, increase of number of cytoplasmic vacuoles, chromatin condensation, invaginations of the nuclear envelope, presence of cytoplasmic inclusion bodies, and alterations in the size and morphology of mitochondria. At 15 μM HgCl 2 apoptotic signs included membrane blebbing, chromatin condensation, mitochondrial alterations, apoptotic bodies, and nuclear envelope rupture. Using confocal microscopy and the mitochondrial specific dye MitoTracker Red, it was possible to establish qualitative changes induced by mercury on the mitochondrial membrane potential after incubation of the cells for 6 and 9 h with 15 μM HgCl 2 . This effect was not observed at short times

  9. A comparison of global optimization algorithms with standard benchmark functions and real-world applications using Energy Plus

    Energy Technology Data Exchange (ETDEWEB)

    Kamph, Jerome Henri; Robinson, Darren; Wetter, Michael

    2009-09-01

    There is an increasing interest in the use of computer algorithms to identify combinations of parameters which optimise the energy performance of buildings. For such problems, the objective function can be multi-modal and needs to be approximated numerically using building energy simulation programs. As these programs contain iterative solution algorithms, they introduce discontinuities in the numerical approximation to the objective function. Metaheuristics often work well for such problems, but their convergence to a global optimum cannot be established formally. Moreover, different algorithms tend to be suited to particular classes of optimization problems. To shed light on this issue we compared the performance of two metaheuristics, the hybrid CMA-ES/HDE and the hybrid PSO/HJ, in minimizing standard benchmark functions and real-world building energy optimization problems of varying complexity. From this we find that the CMA-ES/HDE performs well on more complex objective functions, but that the PSO/HJ more consistently identifies the global minimum for simpler objective functions. Both identified similar values in the objective functions arising from energy simulations, but with different combinations of model parameters. This may suggest that the objective function is multi-modal. The algorithms also correctly identified some non-intuitive parameter combinations that were caused by a simplified control sequence of the building energy system that does not represent actual practice, further reinforcing their utility.

  10. Antibody to gp41 MPER alters functional properties of HIV-1 Env without complete neutralization.

    Directory of Open Access Journals (Sweden)

    Arthur S Kim

    2014-07-01

    Full Text Available Human antibody 10E8 targets the conserved membrane proximal external region (MPER of envelope glycoprotein (Env subunit gp41 and neutralizes HIV-1 with exceptional potency. Remarkably, HIV-1 containing mutations that reportedly knockout 10E8 binding to linear MPER peptides are partially neutralized by 10E8, producing a local plateau in the dose response curve. Here, we found that virus partially neutralized by 10E8 becomes significantly less neutralization sensitive to various MPER antibodies and to soluble CD4 while becoming significantly more sensitive to antibodies and fusion inhibitors against the heptad repeats of gp41. Thus, 10E8 modulates sensitivity of Env to ligands both pre- and post-receptor engagement without complete neutralization. Partial neutralization by 10E8 was influenced at least in part by perturbing Env glycosylation. With unliganded Env, 10E8 bound with lower apparent affinity and lower subunit occupancy to MPER mutant compared to wild type trimers. However, 10E8 decreased functional stability of wild type Env while it had an opposite, stabilizing effect on MPER mutant Envs. Clade C isolates with natural MPER polymorphisms also showed partial neutralization by 10E8 with altered sensitivity to various gp41-targeted ligands. Our findings suggest a novel mechanism of virus neutralization by demonstrating how antibody binding to the base of a trimeric spike cross talks with adjacent subunits to modulate Env structure and function. The ability of an antibody to stabilize, destabilize, partially neutralize as well as alter neutralization sensitivity of a virion spike pre- and post-receptor engagement may have implications for immunotherapy and vaccine design.

  11. Tributyltin exposure alters cytokine levels in mouse serum.

    Science.gov (United States)

    Lawrence, Shanieek; Pellom, Samuel T; Shanker, Anil; Whalen, Margaret M

    2016-11-01

    Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, keratinocyte chemoattractant (KC), macrophage inflammatory protein 1β (MIP), MIP2 and regulated on activation normal T-cell-expressed and secreted (RANTES) was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40 and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in the serum of mice exposed to TBT for less than 24 h. Levels of IL1β, IL-12 βp40, IL-5 and IL-15 were also modulated in mouse serum, depending on the specific experiment and exposure level. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines.

  12. Altered intrinsic functional coupling between core neurocognitive networks in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Deepti Putcha

    2015-01-01

    Full Text Available Parkinson's disease (PD is largely attributed to disruptions in the nigrostriatal dopamine system. These neurodegenerative changes may also have a more global effect on intrinsic brain organization at the cortical level. Functional brain connectivity between neurocognitive systems related to cognitive processing is critical for effective neural communication, and is disrupted across neurological disorders. Three core neurocognitive networks have been established as playing a critical role in the pathophysiology of many neurological disorders: the default-mode network (DMN, the salience network (SN, and the central executive network (CEN. In healthy adults, DMN–CEN interactions are anti-correlated while SN–CEN interactions are strongly positively correlated even at rest, when individuals are not engaging in any task. These intrinsic between-network interactions at rest are necessary for efficient suppression of the DMN and activation of the CEN during a range of cognitive tasks. To identify whether these network interactions are disrupted in individuals with PD, we used resting state functional magnetic resonance imaging (rsfMRI to compare between-network connectivity between 24 PD participants and 20 age-matched controls (MC. In comparison to the MC, individuals with PD showed significantly less SN–CEN coupling and greater DMN–CEN coupling during rest. Disease severity, an index of striatal dysfunction, was related to reduced functional coupling between the striatum and SN. These results demonstrate that individuals with PD have a dysfunctional pattern of interaction between core neurocognitive networks compared to what is found in healthy individuals, and that interaction between the SN and the striatum is even more profoundly disrupted in those with greater disease severity.

  13. Mutations in the catalytic loop HRD motif alter the activity and function of Drosophila Src64.

    Directory of Open Access Journals (Sweden)

    Taylor C Strong

    Full Text Available The catalytic loop HRD motif is found in most protein kinases and these amino acids are predicted to perform functions in catalysis, transition to, and stabilization of the active conformation of the kinase domain. We have identified mutations in a Drosophila src gene, src64, that alter the three HRD amino acids. We have analyzed the mutants for both biochemical activity and biological function during development. Mutation of the aspartate to asparagine eliminates biological function in cytoskeletal processes and severely reduces fertility, supporting the amino acid's critical role in enzymatic activity. The arginine to cysteine mutation has little to no effect on kinase activity or cytoskeletal reorganization, suggesting that the HRD arginine may not be critical for coordinating phosphotyrosine in the active conformation. The histidine to leucine mutant retains some kinase activity and biological function, suggesting that this amino acid may have a biochemical function in the active kinase that is independent of its side chain hydrogen bonding interactions in the active site. We also describe the phenotypic effects of other mutations in the SH2 and tyrosine kinase domains of src64, and we compare them to the phenotypic effects of the src64 null allele.

  14. Brain Oscillatory Correlates of Altered Executive Functioning in Positive and Negative Symptomatic Schizophrenia Patients and Healthy Controls.

    Science.gov (United States)

    Berger, Barbara; Minarik, Tamas; Griesmayr, Birgit; Stelzig-Schoeler, Renate; Aichhorn, Wolfgang; Sauseng, Paul

    2016-01-01

    Working Memory and executive functioning deficits are core characteristics of patients suffering from schizophrenia. Electrophysiological research indicates that altered patterns of neural oscillatory mechanisms underpinning executive functioning are associated with the psychiatric disorder. Such brain oscillatory changes have been found in local amplitude differences at gamma and theta frequencies in task-specific cortical areas. Moreover, interregional interactions are also disrupted as signified by decreased phase coherence of fronto-posterior theta activity in schizophrenia patients. However, schizophrenia is not a one-dimensional psychiatric disorder but has various forms and expressions. A common distinction is between positive and negative symptomatology but most patients have both negative and positive symptoms to some extent. Here, we examined three groups-healthy controls, predominantly negative, and predominantly positive symptomatic schizophrenia patients-when performing a working memory task with increasing cognitive demand and increasing need for executive control. We analyzed brain oscillatory activity in the three groups separately and investigated how predominant symptomatology might explain differences in brain oscillatory patterns. Our results indicate that differences in task specific fronto-posterior network activity (i.e., executive control network) expressed by interregional phase synchronization are able to account for working memory dysfunctions between groups. Local changes in the theta and gamma frequency range also show differences between patients and healthy controls, and more importantly, between the two patient groups. We conclude that differences in oscillatory brain activation patterns related to executive processing can be an indicator for positive and negative symptomatology in schizophrenia. Furthermore, changes in cognitive and especially executive functioning in patients are expressed by alterations in a task-specific fronto

  15. Short-term parasite-infection alters already the biomass, activity and functional diversity of soil microbial communities

    Science.gov (United States)

    Li, Jun-Min; Jin, Ze-Xin; Hagedorn, Frank; Li, Mai-He

    2014-11-01

    Native parasitic plants may be used to infect and control invasive plants. We established microcosms with invasive Mikania micrantha and native Coix lacryma-jobi growing in mixture on native soils, with M. micrantha being infected by parasitic Cuscuta campestris at four intensity levels for seven weeks to estimate the top-down effects of plant parasitism on the biomass and functional diversity of soil microbial communities. Parasitism significantly decreased root biomass and altered soil microbial communities. Soil microbial biomass decreased, but soil respiration increased at the two higher infection levels, indicating a strong stimulation of soil microbial metabolic activity (+180%). Moreover, a Biolog assay showed that the infection resulted in a significant change in the functional diversity indices of soil microbial communities. Pearson correlation analysis indicated that microbial biomass declined significantly with decreasing root biomass, particularly of the invasive M. micrantha. Also, the functional diversity indices of soil microbial communities were positively correlated with soil microbial biomass. Therefore, the negative effects on the biomass, activity and functional diversity of soil microbial community by the seven week long plant parasitism was very likely caused by decreased root biomass and root exudation of the invasive M. micrantha.

  16. Sport-specific endurance plank test for evaluation of global core muscle function.

    Science.gov (United States)

    Tong, Tom K; Wu, Shing; Nie, Jinlei

    2014-02-01

    To examine the validity and reliability of a sports-specific endurance plank test for the evaluation of global core muscle function. Repeated-measures study. Laboratory environment. Twenty-eight male and eight female young athletes. Surface electromyography (sEMG) of selected trunk flexors and extensors, and an intervention of pre-fatigue core workout were applied for test validation. Intraclass correlation coefficient (ICC), coefficient of variation (CV), and the measurement bias ratio */÷ ratio limits of agreement (LOA) were calculated to assess reliability and measurement error. Test validity was shown by the sEMG of selected core muscles, which indicated >50% increase in muscle activation during the test; and the definite discrimination of the ∼30% reduction in global core muscle endurance subsequent to a pre-fatigue core workout. For test-retest reliability, when the first attempt of three repeated trials was considered as familiarisation, the ICC was 0.99 (95% CI: 0.98-0.99), CV was 2.0 ± 1.56% and the measurement bias ratio */÷ ratio LOA was 0.99 */÷ 1.07. The findings suggest that the sport-specific endurance plank test is a valid, reliable and practical method for assessing global core muscle endurance in athletes given that at least one familiarisation trial takes place prior to measurement. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Towards Finding the Global Minimum of the D-Wave Objective Function for Improved Neural Network Regressions

    Science.gov (United States)

    Dorband, J. E.

    2017-12-01

    The D-Wave 2X has successfully been used for regression analysis to derive carbon flux data from OCO-2 CO2 concentration using neural networks. The samples returned from the D-Wave should represent the minimum of an objective function presented to it. An accurate as possible minimum function value is needed for this analysis. Samples from the D-Wave are near minimum, but seldom are the global minimum of the function due to quantum noise. Two methods for improving the accuracy of minimized values represented by the samples returned from the D-Wave are presented. The first method finds a new sample with a minimum value near each returned D-Wave sample. The second method uses all the returned samples to find a more global minimum sample. We present three use-cases performed using the former method. In the first use case, it is demonstrated that an objective function with random qubits and coupler coefficients had an improved minimum. In the second use case, the samples corrected by the first method can improve the training of a Boltzmann machine neural network. The third use case demonstrated that using the first method can improve virtual qubit accuracy.The later method was also performed on the first use case.

  18. Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID.

    Science.gov (United States)

    Sauer, Aisha V; Brigida, Immacolata; Carriglio, Nicola; Hernandez, Raisa Jofra; Scaramuzza, Samantha; Clavenna, Daniela; Sanvito, Francesca; Poliani, Pietro L; Gagliani, Nicola; Carlucci, Filippo; Tabucchi, Antonella; Roncarolo, Maria Grazia; Traggiai, Elisabetta; Villa, Anna; Aiuti, Alessandro

    2012-02-09

    Adenosine acts as anti-inflammatory mediator on the immune system and has been described in regulatory T cell (Treg)-mediated suppression. In the absence of adenosine deaminase (ADA), adenosine and other purine metabolites accumulate, leading to severe immunodeficiency with recurrent infections (ADA-SCID). Particularly ADA-deficient patients with late-onset forms and after enzyme replacement therapy (PEG-ADA) are known to manifest immune dysregulation. Herein we provide evidence that alterations in the purine metabolism interfere with Treg function, thereby contributing to autoimmune manifestations in ADA deficiency. Tregs isolated from PEG-ADA-treated patients are reduced in number and show decreased suppressive activity, whereas they are corrected after gene therapy. Untreated murine ADA(-/-) Tregs show alterations in the plasma membrane CD39/CD73 ectonucleotidase machinery and limited suppressive activity via extracellular adenosine. PEG-ADA-treated mice developed multiple autoantibodies and hypothyroidism in contrast to mice treated with bone marrow transplantation or gene therapy. Tregs isolated from PEG-ADA-treated mice lacked suppressive activity, suggesting that this treatment interferes with Treg functionality. The alterations in the CD39/CD73 adenosinergic machinery and loss of function in ADA-deficient Tregs provide new insights into a predisposition to autoimmunity and the underlying mechanisms causing defective peripheral tolerance in ADA-SCID.

  19. The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in Vivo

    Directory of Open Access Journals (Sweden)

    Yubang Wang

    2015-12-01

    Full Text Available This study was aimed to investigate whether vitamin A deficiency could alter P-GP expression and function in tissues of rats and whether such effects affected the drug distribution in vivo of vitamin A-deficient rats. We induced vitamin A-deficient rats by giving them a vitamin A-free diet for 12 weeks. Then, Abcb1/P-GP expression was evaluated by qRT-PCR and Western blot. qRT-PCR analysis revealed that Abcb1a mRNA levels were increased in hippocampus and liver. In kidney, it only showed an upward trend. Abcb1b mRNA levels were increased in hippocampus, but decreased in cerebral cortex, liver and kidney. Western blot results were in good accordance with the alterations of Abcb1b mRNA levels. P-GP function was investigated through tissue distribution and body fluid excretion of rhodamine 123 (Rho123, and the results proclaimed that P-GP activities were also in good accordance with P-GP expression in cerebral cortex, liver and kidney. The change of drug distribution was also investigated through the tissue distribution of vincristine, and the results showed a significantly upward trend in all indicated tissues of vitamin A-deficient rats. In conclusion, vitamin A deficiency may alter Abcb1/P-GP expression and function in rat tissues, and the alterations may increase drug activity/toxicity through the increase of tissue accumulation.

  20. Alteration of rhythmic unimanual tapping and anti-phase bimanual coordination in Alzheimer's disease: A sign of inter-hemispheric disconnection?

    Science.gov (United States)

    Martin, Elodie; Blais, Mélody; Albaret, Jean-Michel; Pariente, Jérémie; Tallet, Jessica

    2017-10-01

    Little attention is paid to motor control in Alzheimer's disease (AD) although it is a relevant sign of central nervous system integrity and functioning. In particular, unimanual and bimanual tapping is a relevant paradigm because it requires intra- and inter-hemispheric transfer (IHT). Previous results indicate that both unimanual and anti-phase tapping requires more IHT than in-phase tapping, especially produced without external stimulation. The aim of the present study was to test the production of unimanual, bimanual in-phase and anti-phase tapping with a synchronization-continuation paradigm with and without visual stimulation in AD patients (N=9) and control participants (N=12). In accordance with our hypothesis, these results suggest that unimanual and anti-phase tapping is more altered in AD than in control participants. Moreover, performance is globally more variable in the AD group. These alterations are discussed in terms of possible IHT modulation, in line with functional and structural findings in AD, revealing changes in the connectivity of brain regions across hemispheres and white matter damage. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Modeling resting-state functional networks when the cortex falls asleep: local and global changes.

    Science.gov (United States)

    Deco, Gustavo; Hagmann, Patric; Hudetz, Anthony G; Tononi, Giulio

    2014-12-01

    The transition from wakefulness to sleep represents the most conspicuous change in behavior and the level of consciousness occurring in the healthy brain. It is accompanied by similarly conspicuous changes in neural dynamics, traditionally exemplified by the change from "desynchronized" electroencephalogram activity in wake to globally synchronized slow wave activity of early sleep. However, unit and local field recordings indicate that the transition is more gradual than it might appear: On one hand, local slow waves already appear during wake; on the other hand, slow sleep waves are only rarely global. Studies with functional magnetic resonance imaging also reveal changes in resting-state functional connectivity (FC) between wake and slow wave sleep. However, it remains unclear how resting-state networks may change during this transition period. Here, we employ large-scale modeling of the human cortico-cortical anatomical connectivity to evaluate changes in resting-state FC when the model "falls asleep" due to the progressive decrease in arousal-promoting neuromodulation. When cholinergic neuromodulation is parametrically decreased, local slow waves appear, while the overall organization of resting-state networks does not change. Furthermore, we show that these local slow waves are structured macroscopically in networks that resemble the resting-state networks. In contrast, when the neuromodulator decrease further to very low levels, slow waves become global and resting-state networks merge into a single undifferentiated, broadly synchronized network. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Structural connectivity in schizophrenia and its impact on the dynamics of spontaneous functional networks

    International Nuclear Information System (INIS)

    Cabral, Joana; Fernandes, Henrique M.; Van Hartevelt, Tim J.; Kringelbach, Morten L.; James, Anthony C.; Deco, Gustavo

    2013-01-01

    The neuropathology of schizophrenia remains unclear. Some insight has come from modern neuroimaging techniques, which offer an unparalleled opportunity to explore in vivo the structure and function of the brain. Using functional magnetic resonance imaging, it has been found that the large-scale resting-state functional connectivity (rsFC) in schizophrenia — measured as the temporal correlations of the blood-oxygen-level-dependent (BOLD) signal — exhibit altered network topology, with lower small-world index. The origin of these rsFC alterations and link with the underlying structural connectivity remain unclear. In this work, we used a computational model of spontaneous large-scale brain activity to explore the role of the structural connectivity in the large-scale dynamics of the brain in health and schizophrenia. The structural connectomes from 15 adolescent patients with early-onset schizophrenia and 15 age- and gender-matched controls were built from diffusion tensor imaging data to detect the white matter tracts between 90 brain areas. Brain areas, simulated using a reduced dynamic mean-field model, receive excitatory input from other areas in proportion to the number of fibre tracts between them. The simulated mean field activity was transformed into BOLD signal, and the properties of the simulated functional networks were analyzed. Our results suggest that the functional alterations observed in schizophrenia are not directly linked to alterations in the structural topology. Instead, subtly randomized and less small-world functional networks appear when the brain operates with lower global coupling, which shifts the dynamics from the optimal healthy regime

  3. Structural connectivity in schizophrenia and its impact on the dynamics of spontaneous functional networks

    Energy Technology Data Exchange (ETDEWEB)

    Cabral, Joana [Theoretical and Computational Neuroscience Group, Center of Brain and Cognition, Universitat Pompeu Fabra, Barcelona 08018 (Spain); Department of Psychiatry, University of Oxford, Oxford OX3 7JX (United Kingdom); Fernandes, Henrique M.; Van Hartevelt, Tim J.; Kringelbach, Morten L. [Department of Psychiatry, University of Oxford, Oxford OX3 7JX (United Kingdom); Center of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus (Denmark); James, Anthony C. [Department of Psychiatry, University of Oxford, Oxford OX3 7JX (United Kingdom); Highfield Unit, Warneford Hospital, Oxford OX3 7JX (United Kingdom); Deco, Gustavo [Theoretical and Computational Neuroscience Group, Center of Brain and Cognition, Universitat Pompeu Fabra, Barcelona 08018 (Spain); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010 (Spain)

    2013-12-15

    The neuropathology of schizophrenia remains unclear. Some insight has come from modern neuroimaging techniques, which offer an unparalleled opportunity to explore in vivo the structure and function of the brain. Using functional magnetic resonance imaging, it has been found that the large-scale resting-state functional connectivity (rsFC) in schizophrenia — measured as the temporal correlations of the blood-oxygen-level-dependent (BOLD) signal — exhibit altered network topology, with lower small-world index. The origin of these rsFC alterations and link with the underlying structural connectivity remain unclear. In this work, we used a computational model of spontaneous large-scale brain activity to explore the role of the structural connectivity in the large-scale dynamics of the brain in health and schizophrenia. The structural connectomes from 15 adolescent patients with early-onset schizophrenia and 15 age- and gender-matched controls were built from diffusion tensor imaging data to detect the white matter tracts between 90 brain areas. Brain areas, simulated using a reduced dynamic mean-field model, receive excitatory input from other areas in proportion to the number of fibre tracts between them. The simulated mean field activity was transformed into BOLD signal, and the properties of the simulated functional networks were analyzed. Our results suggest that the functional alterations observed in schizophrenia are not directly linked to alterations in the structural topology. Instead, subtly randomized and less small-world functional networks appear when the brain operates with lower global coupling, which shifts the dynamics from the optimal healthy regime.

  4. The ecological limits of hydrologic alteration (ELOHA): A new framework for developing regional environmental flow standards

    Science.gov (United States)

    Poff, N.L.; Richter, B.D.; Arthington, A.H.; Bunn, S.E.; Naiman, R.J.; Kendy, E.; Acreman, M.; Apse, C.; Bledsoe, B.P.; Freeman, Mary C.; Henriksen, J.; Jacobson, R.B.; Kennen, J.G.; Merritt, D.M.; O'Keeffe, J. H.; Olden, J.D.; Rogers, K.; Tharme, R.E.; Warner, A.

    2010-01-01

    The flow regime is a primary determinant of the structure and function of aquatic and riparian ecosystems for streams and rivers. Hydrologic alteration has impaired riverine ecosystems on a global scale, and the pace and intensity of human development greatly exceeds the ability of scientists to assess the effects on a river-by-river basis. Current scientific understanding of hydrologic controls on riverine ecosystems and experience gained from individual river studies support development of environmental flow standards at the regional scale. 2. This paper presents a consensus view from a group of international scientists on a new framework for assessing environmental flow needs for many streams and rivers simultaneously to foster development and implementation of environmental flow standards at the regional scale. This framework, the ecological limits of hydrologic alteration (ELOHA), is a synthesis of a number of existing hydrologic techniques and environmental flow methods that are currently being used to various degrees and that can support comprehensive regional flow management. The flexible approach allows scientists, water-resource managers and stakeholders to analyse and synthesise available scientific information into ecologically based and socially acceptable goals and standards for management of environmental flows. 3. The ELOHA framework includes the synthesis of existing hydrologic and ecological databases from many rivers within a user-defined region to develop scientifically defensible and empirically testable relationships between flow alteration and ecological responses. These relationships serve as the basis for the societally driven process of developing regional flow standards. This is to be achieved by first using hydrologic modelling to build a 'hydrologic foundation' of baseline and current hydrographs for stream and river segments throughout the region. Second, using a set of ecologically relevant flow variables, river segments within the

  5. Global equivalent magnetization of the oceanic lithosphere

    Science.gov (United States)

    Dyment, J.; Choi, Y.; Hamoudi, M.; Lesur, V.; Thebault, E.

    2015-11-01

    As a by-product of the construction of a new World Digital Magnetic Anomaly Map over oceanic areas, we use an original approach based on the global forward modeling of seafloor spreading magnetic anomalies and their comparison to the available marine magnetic data to derive the first map of the equivalent magnetization over the World's ocean. This map reveals consistent patterns related to the age of the oceanic lithosphere, the spreading rate at which it was formed, and the presence of mantle thermal anomalies which affects seafloor spreading and the resulting lithosphere. As for the age, the equivalent magnetization decreases significantly during the first 10-15 Myr after its formation, probably due to the alteration of crustal magnetic minerals under pervasive hydrothermal alteration, then increases regularly between 20 and 70 Ma, reflecting variations in the field strength or source effects such as the acquisition of a secondary magnetization. As for the spreading rate, the equivalent magnetization is twice as strong in areas formed at fast rate than in those formed at slow rate, with a threshold at ∼40 km/Myr, in agreement with an independent global analysis of the amplitude of Anomaly 25. This result, combined with those from the study of the anomalous skewness of marine magnetic anomalies, allows building a unified model for the magnetic structure of normal oceanic lithosphere as a function of spreading rate. Finally, specific areas affected by thermal mantle anomalies at the time of their formation exhibit peculiar equivalent magnetization signatures, such as the cold Australian-Antarctic Discordance, marked by a lower magnetization, and several hotspots, marked by a high magnetization.

  6. Explicit verbal memory impairments associated with brain functional deficits and morphological alterations in patients with generalized anxiety disorder.

    Science.gov (United States)

    Moon, Chung-Man; Yang, Jong-Chul; Jeong, Gwang-Woo

    2015-11-01

    Generalized anxiety disorder (GAD) is associated with brain function and morphological alterations. This study investigated explicit verbal memory impairment in patients with GAD in terms of brain functional deficits in combination with morphologic changes. Seventeen patients with GAD and 17 healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted MRI and fMR imaging at 3 T during explicit verbal memory tasks with emotionally neutral and anxiety-inducing words. In response to the neutral words, the patients showed significantly lower activities in the regions of the hippocampus (Hip), middle cingulate gyrus (MCG), putamen (Pu) and head of the caudate nucleus (HCd) compared with healthy controls. In response to the anxiety-inducing words, the patients showed significantly higher activities in the ventrolateral prefrontal cortex and precentral gyrus. However, they showed lower activities in the Hip, MCG, Pu and HCd. In addition, patients with GAD showed a significant reduction in gray matter volumes, especially in the regions of the Hip, midbrain, thalamus, insula and superior temporal gyrus, compared with healthy controls. This study examined a small sample sizes in each of the groups, and there was no consideration of a medication effect on brain activity and volume changes. This study provides evidence for the association between brain functional deficits and morphometric alterations in an explicit verbal memory task for patients with GAD. This finding is helpful for understanding explicit verbal memory impairment in connection with GAD symptoms. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Disrupted functional connectome in antisocial personality disorder

    Science.gov (United States)

    Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen

    2017-01-01

    Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD. PMID:27541949

  8. [Brain plastic alterations in subjects with chronic right-sided sensorineural hearing loss: a resting-state MRI study].

    Science.gov (United States)

    Zhang, L L; Gong, J P; Xu, Y W; Liu, B

    2016-06-21

    To investigate the nodal properties and reorganization of whole-brain functional network in subjects with severe right-sided SNHL. From June 2012 to June 2013, a total of 19 patients with severe right-sided SNHL were collected from Zhongda Hospital or the recruitment advertising along with 31 healthy controls.Based on the graph-theoretical analysis, the whole-brain functional networks were constructed using the BOLD-fMRI data of all subjects.Two sample two-tailed t-tests were used to investigate the differences between two groups in nodal metrics, such as node degree, node betweenness, node global efficiency and node local efficiency.All metrics were corrected by multiple comparisons.Partial correlation analysis was used to estimate the relationship between the significant metrics and the duration or severity of hearing loss. The right-sided SNHL showed significantly increased betweenness centrality in left supramarginal gyrus and right fusiform.However, other nodal parameters showed no statistical difference.Besides, patients exhibited no significant association between the altered metrics and clinical variables. Alterations of local topological properties may underlie cerebral cross-modal plastic reorganization in visual or speech-related regions in severe right-sided SNHL patients.

  9. Transient global amnesia and functional retrograde amnesia: contrasting examples of episodic memory loss.

    OpenAIRE

    Kritchevsky, M; Zouzounis, J; Squire, L R

    1997-01-01

    We studied 11 patients with transient global amnesia (TGA) and ten patients with functional retrograde amnesia (FRA). Patients with TGA had a uniform clinical picture: a severe, relatively isolated amnesic syndrome that started suddenly, persisted for 4-12 h, and then gradually improved to essentially normal over the next 12-24 h. During the episode, the patients had severe anterograde amnesia for verbal and non-verbal material and retrograde amnesia that typically covered at least two decade...

  10. Global warming alters sound transmission: differential impact on the prey detection ability of echolocating bats

    Science.gov (United States)

    Luo, Jinhong; Koselj, Klemen; Zsebők, Sándor; Siemers, Björn M.; Goerlitz, Holger R.

    2014-01-01

    Climate change impacts the biogeography and phenology of plants and animals, yet the underlying mechanisms are little known. Here, we present a functional link between rising temperature and the prey detection ability of echolocating bats. The maximum distance for echo-based prey detection is physically determined by sound attenuation. Attenuation is more pronounced for high-frequency sound, such as echolocation, and is a nonlinear function of both call frequency and ambient temperature. Hence, the prey detection ability, and thus possibly the foraging efficiency, of echolocating bats and susceptible to rising temperatures through climate change. Using present-day climate data and projected temperature rises, we modelled this effect for the entire range of bat call frequencies and climate zones around the globe. We show that depending on call frequency, the prey detection volume of bats will either decrease or increase: species calling above a crossover frequency will lose and species emitting lower frequencies will gain prey detection volume, with crossover frequency and magnitude depending on the local climatic conditions. Within local species assemblages, this may cause a change in community composition. Global warming can thus directly affect the prey detection ability of individual bats and indirectly their interspecific interactions with competitors and prey. PMID:24335559

  11. Global warming alters sound transmission: differential impact on the prey detection ability of echolocating bats.

    Science.gov (United States)

    Luo, Jinhong; Koselj, Klemen; Zsebok, Sándor; Siemers, Björn M; Goerlitz, Holger R

    2014-02-06

    Climate change impacts the biogeography and phenology of plants and animals, yet the underlying mechanisms are little known. Here, we present a functional link between rising temperature and the prey detection ability of echolocating bats. The maximum distance for echo-based prey detection is physically determined by sound attenuation. Attenuation is more pronounced for high-frequency sound, such as echolocation, and is a nonlinear function of both call frequency and ambient temperature. Hence, the prey detection ability, and thus possibly the foraging efficiency, of echolocating bats and susceptible to rising temperatures through climate change. Using present-day climate data and projected temperature rises, we modelled this effect for the entire range of bat call frequencies and climate zones around the globe. We show that depending on call frequency, the prey detection volume of bats will either decrease or increase: species calling above a crossover frequency will lose and species emitting lower frequencies will gain prey detection volume, with crossover frequency and magnitude depending on the local climatic conditions. Within local species assemblages, this may cause a change in community composition. Global warming can thus directly affect the prey detection ability of individual bats and indirectly their interspecific interactions with competitors and prey.

  12. Global alteration of microRNAs and transposon-derived small RNAs in cotton (Gossypium hirsutum) during Cotton leafroll dwarf polerovirus (CLRDV) infection.

    Science.gov (United States)

    Romanel, Elisson; Silva, Tatiane F; Corrêa, Régis L; Farinelli, Laurent; Hawkins, Jennifer S; Schrago, Carlos E G; Vaslin, Maite F S

    2012-11-01

    Small RNAs (sRNAs) are a class of non-coding RNAs ranging from 20- to 40-nucleotides (nts) that are present in most eukaryotic organisms. In plants, sRNAs are involved in the regulation of development, the maintenance of genome stability and the antiviral response. Viruses, however, can interfere with and exploit the silencing-based regulatory networks, causing the deregulation of sRNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs). To understand the impact of viral infection on the plant sRNA pathway, we deep sequenced the sRNAs in cotton leaves infected with Cotton leafroll dwarf virus (CLRDV), which is a member of the economically important virus family Luteoviridae. A total of 60 putative conserved cotton miRNAs were identified, including 19 new miRNA families that had not been previously described in cotton. Some of these miRNAs were clearly misregulated during viral infection, and their possible role in symptom development and disease progression is discussed. Furthermore, we found that the 24-nt heterochromatin-associated siRNAs were quantitatively and qualitatively altered in the infected plant, leading to the reactivation of at least one cotton transposable element. This is the first study to explore the global alterations of sRNAs in virus-infected cotton plants. Our results indicate that some CLRDV-induced symptoms may be correlated with the deregulation of miRNA and/or epigenetic networks.

  13. Tai Ji Quan and global cognitive function in older adults with cognitive impairment: a pilot study.

    Science.gov (United States)

    Li, Fuzhong; Harmer, Peter; Liu, Yu; Chou, Li-Shan

    2014-01-01

    This study evaluated whether Tai Ji Quan: Moving for Better Balance (TJQMBB) could improve global cognitive function in older adults with cognitive impairment. Using a nonrandomized control group pretest-posttest design, participants aged ≥65 years who scored between 20 and 25 on the Mini-Mental State Examination (MMSE) were allocated into either a 14-week TJQMBB program (n=22) or a control group (n=24). The primary outcome was MMSE as a measure of global cognitive function with secondary outcomes of 50-ft speed walk, Timed Up&Go, and Activities-Specific Balance Confidence (ABC) scale. At 14 weeks, Tai Ji Quan participants showed significant improvement on MMSE (mean=2.26, pJi Quan participants performed significantly better compared to the controls in both physical performance and balance efficacy measures (p<0.05). Improvement in cognition as measured by MMSE was related to improved physical performance and balance efficacy. These results provide preliminary evidence of the utility of the TJQMBB program to promote cognitive function in older adults in addition to physical benefits. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  14. Modeling large-scale human alteration of land surface hydrology and climate

    Science.gov (United States)

    Pokhrel, Yadu N.; Felfelani, Farshid; Shin, Sanghoon; Yamada, Tomohito J.; Satoh, Yusuke

    2017-12-01

    Rapidly expanding human activities have profoundly affected various biophysical and biogeochemical processes of the Earth system over a broad range of scales, and freshwater systems are now amongst the most extensively altered ecosystems. In this study, we examine the human-induced changes in land surface water and energy balances and the associated climate impacts using a coupled hydrological-climate model framework which also simulates the impacts of human activities on the water cycle. We present three sets of analyses using the results from two model versions—one with and the other without considering human activities; both versions are run in offline and coupled mode resulting in a series of four experiments in total. First, we examine climate and human-induced changes in regional water balance focusing on the widely debated issue of the desiccation of the Aral Sea in central Asia. Then, we discuss the changes in surface temperature as a result of changes in land surface energy balance due to irrigation over global and regional scales. Finally, we examine the global and regional climate impacts of increased atmospheric water vapor content due to irrigation. Results indicate that the direct anthropogenic alteration of river flow in the Aral Sea basin resulted in the loss of 510 km3 of water during the latter half of the twentieth century which explains about half of the total loss of water from the sea. Results of irrigation-induced changes in surface energy balance suggest a significant surface cooling of up to 3.3 K over 1° grids in highly irrigated areas but a negligible change in land surface temperature when averaged over sufficiently large global regions. Results from the coupled model indicate a substantial change in 2 m air temperature and outgoing longwave radiation due to irrigation, highlighting the non-local (regional and global) implications of irrigation. These results provide important insights on the direct human alteration of land surface

  15. Altered neuromuscular control and ankle joint kinematics during walking in subjects with functional instability of the ankle joint.

    Science.gov (United States)

    Delahunt, Eamonn; Monaghan, Kenneth; Caulfield, Brian

    2006-12-01

    The ankle joint requires very precise neuromuscular control during the transition from terminal swing to the early stance phase of the gait cycle. Altered ankle joint arthrokinematics and muscular activity have been cited as potential factors that may lead to an inversion sprain during the aforementioned time periods. However, to date, no study has investigated patterns of muscle activity and 3D joint kinematics simultaneously in a group of subjects with functional instability compared with a noninjured control group during these phases of the gait cycle. To compare the patterns of lower limb 3D joint kinematics and electromyographic activity during treadmill walking in a group of subjects with functional instability with those observed in a control group. Controlled laboratory study. Three-dimensional angular velocities and displacements of the hip, knee, and ankle joints, as well as surface electromyography of the rectus femoris, peroneus longus, tibialis anterior, and soleus muscles, were recorded simultaneously while subjects walked on a treadmill at a velocity of 4 km/h. Before heel strike, subjects with functional instability exhibited a decrease in vertical foot-floor clearance (12.62 vs 22.84 mm; P joint before, at, and immediately after heel strike (1.69 degrees , 2.10 degrees , and -0.09 degrees vs -1.43 degrees , -1.43 degrees , and -2.78 degrees , respectively [minus value = eversion]; P < .05) compared with controls. Subjects with functional instability were also observed to have an increase in peroneus longus integral electromyography during the post-heel strike time period (107.91%.millisecond vs 64.53%.millisecond; P < .01). The altered kinematics observed in this study could explain the reason subjects with functional instability experience repeated episodes of ankle inversion injury in situations with only slight or no external provocation. It is hypothesized that the observed increase in peroneus longus activity may be the result of a change in

  16. Alterations of White Matter Integrity and Hippocampal Functional Connectivity in Type 2 Diabetes Without Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Qian Sun

    2018-03-01

    Full Text Available Aims: To investigate the white matter (WM integrity and hippocampal functional connectivity (FC in type 2 diabetes mellitus (T2DM patients without mild cognitive impairment (MCI by using diffusion tensor imaging (DTI and resting-state functional magnetic resonance imaging (rs-fMRI, respectively.Methods: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS combining region of interests (ROIs analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA, mean diffusivity (MD, λ1 and λ23 and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE and Montreal Cognitive Assessment (MoCA. Brain volumes were also evaluated among these participants.Results: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC. Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex.Conclusions: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated.Highlights-T2DM patients without MCI demonstrated no obvious brain volume decrease.-Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients.-Despite no MCI in T2

  17. Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects

    DEFF Research Database (Denmark)

    Gliemann, Lasse; Rytter, Nicolai; Lindskrog, Mads

    2017-01-01

    Endothelial mechanotransduction is important for vascular function but alterations and activation of vascular mechanosensory proteins have not been investigated in humans. In endothelial cell culture, simple sugars effectively impair mechanosensor proteins. To study mechanosensor- and vascular...... by ultrasound doppler. A muscle biopsy was obtained from the thigh muscle before and after acute passive leg movement, to asses the protein amount and phosphorylation status of mechanosensory proteins and NADPH oxidase. The sucrose intervention led to a reduced flow response to passive movement (by 17 ± 2...... %) and to 12 watts of active exercise (by 9 ± 1 %), indicating impaired vascular function. Reduced flow response to passive and active exercise was paralleled by a significant upregulation of Platelet endothelial cell adhesion molecule (PECAM-1), endothelial nitric oxide synthase, NADPH oxidase and the Rho...

  18. One digit interruption: the altered force patterns during functionally cylindrical grasping tasks in patients with trigger digits.

    Directory of Open Access Journals (Sweden)

    Po-Tsun Chen

    Full Text Available Most trigger digit (TD patients complain that they have problems using their hand in daily or occupational tasks due to single or multiple digits being affected. Unfortunately, clinicians do not know much about how this disease affects the subtle force coordination among digits during manipulation. Thus, this study examined the differences in force patterns during cylindrical grasp between TD and healthy subjects. Forty-two TD patients with single digit involvement were included and sorted into four groups based on the involved digits, including thumb, index, middle and ring fingers. Twelve healthy subjects volunteered as healthy controls. Two testing tasks, holding and drinking, were performed by natural grasping with minimal forces. The relations between the force of the thumb and each finger were examined by Pearson correlation coefficients. The force amount and contribution of each digit were compared between healthy controls and each TD group by the independent t test. The results showed all TD groups demonstrated altered correlation patterns of the thumb relative to each finger. Larger forces and higher contributions of the index finger were found during holding by patients with index finger involved, and also during drinking by patients with affected thumb and with affected middle finger. Although no triggering symptom occurred during grasping, the patients showed altered force patterns which may be related to the role of the affected digit in natural grasping function. In conclusion, even if only one digit was affected, the subtle force coordination of all the digits was altered during simple tasks among the TD patients. This study provides the information for the future studies to further comprehend the possible injuries secondary to the altered finger coordination and also to adopt suitable treatment strategies.

  19. One digit interruption: the altered force patterns during functionally cylindrical grasping tasks in patients with trigger digits.

    Science.gov (United States)

    Chen, Po-Tsun; Lin, Chien-Ju; Jou, I-Ming; Chieh, Hsiao-Feng; Su, Fong-Chin; Kuo, Li-Chieh

    2013-01-01

    Most trigger digit (TD) patients complain that they have problems using their hand in daily or occupational tasks due to single or multiple digits being affected. Unfortunately, clinicians do not know much about how this disease affects the subtle force coordination among digits during manipulation. Thus, this study examined the differences in force patterns during cylindrical grasp between TD and healthy subjects. Forty-two TD patients with single digit involvement were included and sorted into four groups based on the involved digits, including thumb, index, middle and ring fingers. Twelve healthy subjects volunteered as healthy controls. Two testing tasks, holding and drinking, were performed by natural grasping with minimal forces. The relations between the force of the thumb and each finger were examined by Pearson correlation coefficients. The force amount and contribution of each digit were compared between healthy controls and each TD group by the independent t test. The results showed all TD groups demonstrated altered correlation patterns of the thumb relative to each finger. Larger forces and higher contributions of the index finger were found during holding by patients with index finger involved, and also during drinking by patients with affected thumb and with affected middle finger. Although no triggering symptom occurred during grasping, the patients showed altered force patterns which may be related to the role of the affected digit in natural grasping function. In conclusion, even if only one digit was affected, the subtle force coordination of all the digits was altered during simple tasks among the TD patients. This study provides the information for the future studies to further comprehend the possible injuries secondary to the altered finger coordination and also to adopt suitable treatment strategies.

  20. Rib cage deformities alter respiratory muscle action and chest wall function in patients with severe osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Antonella LoMauro

    Full Text Available BACKGROUND: Osteogenesis imperfecta (OI is an inherited connective tissue disorder characterized by bone fragility, multiple fractures and significant chest wall deformities. Cardiopulmonary insufficiency is the leading cause of death in these patients. METHODS: Seven patients with severe OI type III, 15 with moderate OI type IV and 26 healthy subjects were studied. In addition to standard spirometry, rib cage geometry, breathing pattern and regional chest wall volume changes at rest in seated and supine position were assessed by opto-electronic plethysmography to investigate if structural modifications of the rib cage in OI have consequences on ventilatory pattern. One-way or two-way analysis of variance was performed to compare the results between the three groups and the two postures. RESULTS: Both OI type III and IV patients showed reduced FVC and FEV(1 compared to predicted values, on condition that updated reference equations are considered. In both positions, ventilation was lower in OI patients than control because of lower tidal volume (p<0.01. In contrast to OI type IV patients, whose chest wall geometry and function was normal, OI type III patients were characterized by reduced (p<0.01 angle at the sternum (pectus carinatum, paradoxical inspiratory inward motion of the pulmonary rib cage, significant thoraco-abdominal asynchronies and rib cage distortions in supine position (p<0.001. CONCLUSIONS: In conclusion, the restrictive respiratory pattern of Osteogenesis Imperfecta is closely related to the severity of the disease and to the sternal deformities. Pectus carinatum characterizes OI type III patients and alters respiratory muscles coordination, leading to chest wall and rib cage distortions and an inefficient ventilator pattern. OI type IV is characterized by lower alterations in the respiratory function. These findings suggest that functional assessment and treatment of OI should be differentiated in these two forms of the

  1. Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronary-artery disease

    International Nuclear Information System (INIS)

    Borer, J.S.; Bacharach, S.L.; Green, M.V.; Kent, K.M.; Epstein, S.E.; Johnston, G.S.

    1977-01-01

    Although coronary angiography defines regions of potential ischemia in patients with coronary-artery disease, accurate assessment of the presence and functional importance of ischemia requires appraisal of regional and global left ventricular function during stress. To perform such assessment, we developed a noninvasive real-time radionuclide cineangiographic procedure permitting continuous monitoring and analysis of left ventricular function during exercise. In 11 patients with coronary disease who had normal regional and global ventricular function at rest, new regions of dysfunction developed during exercise (P less than 0.001), and in 10, global ejection fraction dropped 7 to 47 percent. Fourteen age-matched normal subjects were studied; during exercise none had regional dysfunction, and each increased global ejection fraction (average increase, 23 +- 3 percent [+-S.E.], P less than 0.001 as compared with patients with coronary disease). Radionuclide cineangiography during exercise permits accurate assessment of the presence and functional severity of ischemic heart disease

  2. Cosmic microwave background constraints for global strings and global monopoles

    International Nuclear Information System (INIS)

    Lopez-Eiguren, Asier; Lizarraga, Joanes; Urrestilla, Jon; Hindmarsh, Mark

    2017-01-01

    We present the first cosmic microwave background (CMB) power spectra from numerical simulations of the global O( N ) linear σ-model, with N =2,3, which have global strings and monopoles as topological defects. In order to compute the CMB power spectra we compute the unequal time correlators (UETCs) of the energy-momentum tensor, showing that they fall off at high wave number faster than naive estimates based on the geometry of the defects, indicating non-trivial (anti-)correlations between the defects and the surrounding Goldstone boson field. We obtain source functions for Einstein-Boltzmann solvers from the UETCs, using a recently developed method that improves the modelling at the radiation-matter transition. We show that the interpolation function that mimics the transition is similar to other defect models, but not identical, confirming the non-universality of the interpolation function. The CMB power spectra for global strings and global monopoles have the same overall shape as those obtained using the non-linear σ-model approximation, which is well captured by a large- N calculation. However, the amplitudes are larger than the large- N calculation would naively predict, and in the case of global strings much larger: a factor of 20 at the peak. Finally we compare the CMB power spectra with the latest CMB data in other to put limits on the allowed contribution to the temperature power spectrum at multipole l = 10 of 1.7% for global strings and 2.4% for global monopoles. These limits correspond to symmetry-breaking scales of 2.9× 10 15 GeV (6.3× 10 14 GeV with the expected logarithmic scaling of the effective string tension between the simulation time and decoupling) and 6.4× 10 15 GeV respectively. The bound on global strings is a significant one for the ultra-light axion scenario with axion masses m a ∼< 10 −28 eV . These upper limits indicate that gravitational waves from global topological defects will not be observable at the gravitational wave

  3. Proteome analysis demonstrates profound alterations in human dendritic cell nature by TX527, an analogue of vitamin D

    DEFF Research Database (Denmark)

    Ferreira, G. B.; van Etten, E.; Lage, K.

    2009-01-01

    Structural analogues of vitamin D have been put forward as therapeutic agents able to exploit the immunomodulatory effects of vitamin D, without its undesired calcemic side effects. We have demonstrated that TX527 affects dendritic cell (DC) maturation in vitro, resulting in the generation...... of a tolerogenic cell. In the present study, we aimed to explore the global protein changes induced by the analogue in immature DC (iDC) and mature human DC and to correlate them with alterations in DC morphology and function. Human CD14(+) monocytes were differentiated toward iDC or mature DCs, in the presence...

  4. Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID

    Science.gov (United States)

    Sauer, Aisha V.; Brigida, Immacolata; Carriglio, Nicola; Jofra Hernandez, Raisa; Scaramuzza, Samantha; Clavenna, Daniela; Sanvito, Francesca; Poliani, Pietro L.; Gagliani, Nicola; Carlucci, Filippo; Tabucchi, Antonella; Roncarolo, Maria Grazia; Traggiai, Elisabetta; Villa, Anna

    2012-01-01

    Adenosine acts as anti-inflammatory mediator on the immune system and has been described in regulatory T cell (Treg)–mediated suppression. In the absence of adenosine deaminase (ADA), adenosine and other purine metabolites accumulate, leading to severe immunodeficiency with recurrent infections (ADA-SCID). Particularly ADA-deficient patients with late-onset forms and after enzyme replacement therapy (PEG-ADA) are known to manifest immune dysregulation. Herein we provide evidence that alterations in the purine metabolism interfere with Treg function, thereby contributing to autoimmune manifestations in ADA deficiency. Tregs isolated from PEG-ADA–treated patients are reduced in number and show decreased suppressive activity, whereas they are corrected after gene therapy. Untreated murine ADA−/− Tregs show alterations in the plasma membrane CD39/CD73 ectonucleotidase machinery and limited suppressive activity via extracellular adenosine. PEG-ADA–treated mice developed multiple autoantibodies and hypothyroidism in contrast to mice treated with bone marrow transplantation or gene therapy. Tregs isolated from PEG-ADA–treated mice lacked suppressive activity, suggesting that this treatment interferes with Treg functionality. The alterations in the CD39/CD73 adenosinergic machinery and loss of function in ADA-deficient Tregs provide new insights into a predisposition to autoimmunity and the underlying mechanisms causing defective peripheral tolerance in ADA-SCID. Trials were registered at www.clinicaltrials.gov as NCT00598481/NCT00599781. PMID:22184407

  5. Air Pollution Impacts on Global Crop Productivity and Nitrogen Depositio

    Science.gov (United States)

    Heald, C. L.; Tai, A. P. K.; Val Martin, M.

    2014-12-01

    The biosphere is undeniably transformed by air pollution. Emissions, climate change, and land use change are all expected to substantially alter future air quality. In this presentation, we discuss near-term projections (2050) of air quality impacts on both crop productivity and nitrogen deposition. First, we contrast the relative impacts of ozone air pollution and a warming climate on global crop yields. To do so, we define statistical crop yield functions to a warming climate based on the historical record. We combine these relationships with ozone-damage estimates and apply these to future air quality and climate projections from a global coupled chemistry-climate model (CESM). We find substantial variability in the response, with certain regions or crops more sensitive to ozone pollution and others more sensitive to warming. This work demonstrates that air quality management is a key element to ensuring global food security. Second, we examine the relative impacts of anthropogenic emissions, climate change, and land use change on global nitrogen deposition. Nitrogen deposition has rapidly increased over the Anthropocene. Excess deposition of nitrogen to ecosystems can lead to eutrophication of waters, and a decrease in biodiversity. We use the CESM to investigate two scenarios (RCP 4.5 and RCP8.5) and focus our analysis on the impacts on diverse ecoregions in North America, Europe, and Asia.

  6. Indirect Effects of Global Change: From Physiological and Behavioral Mechanisms to Ecological Consequences.

    Science.gov (United States)

    Gunderson, Alex R; Tsukimura, Brian; Stillman, Jonathon H

    2017-07-01

    A major focus of current ecological research is to understand how global change makes species vulnerable to extirpation. To date, mechanistic ecophysiological analyses of global change vulnerability have focused primarily on the direct effects of changing abiotic conditions on whole-organism physiological traits, such as metabolic rate, locomotor performance, cardiac function, and critical thermal limits. However, species do not live in isolation within their physical environments, and direct effects of climate change are likely to be compounded by indirect effects that result from altered interactions with other species, such as competitors and predators. The Society for Integrative and Comparative Biology 2017 Symposium "Indirect Effects of Global Change: From Physiological and Behavioral Mechanisms to Ecological Consequences" was designed to synthesize multiple approaches to investigating the indirect effects of global change by bringing together researchers that study the indirect effects of global change from multiple perspectives across habitat, type of anthropogenic change, and level of biological organization. Our goal in bringing together researchers from different backgrounds was to foster cross-disciplinary insights into the mechanistic bases and higher-order ecological consequences of indirect effects of global change, and to promote collaboration among fields. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  7. Characteristics of brain functional alterations and task functional magnetic resonance imaging in patients with Cushing’s disease

    Directory of Open Access Journals (Sweden)

    Dan-dan LIU

    2017-08-01

    Full Text Available Objective To analyze the relationship between the brain functional alterations of patients with Cushing's disease (CD and patients' mental symptom by applying the Evaluating Emotional Scales and task functional magnetic resonance imaging (Task fMRI. Methods Task fMRI was performed on 8 patients with diagnosed CD admitted in the Department of Endocrinology of Chinese PLA General Hospital from Nov. 2015 to Nov. 2016 and 21 healthy people with matched age, gender and education level as control. Meanwhile, Self-Rating Depression Scale (SDS, Self-Rating Anxiety Scale (SAS, Positive and Negative Affective Scale (PANAS and Cushing Quality of Life Scale (Cushing QOL were obtained to assess the brain functions. Results Significant depression and anxiety were observed in patients with CD, and their positive affective score was substantially lower while the negative affective score was relatively higher compared with that in the controls. Task fMRI revealed that, when watching the positive pictures, the activation degree of left cerebellum and right postcentral gyrus weakened in CD patients than in the controls, and the positive correlations existed between the activation degree of left cerebellum and the 16 o'clock adrenocorticotrophic hormone (ACTH level, and between the activation degree of right postcentral gyrus and the urinary free cortisol (UFC level in CD patients. In contrast, when watching the negative pictures, the activation degree of left cerebellum, bilateral parahippocampal gyrus and left inferior frontal gyrus was weakened in CD patients than in the controls, and the activation degree of left cerebellum was negatively correlated to the 0 o'clock cortisol level and SAS score, but is positively correlated to the UFC level. When watching the neutral pictures, the activation degree of left cerebellum and left parahippocampal gyrus was weakened in CD patients than in the controls. Conclusions CD patients may have impaired brain function with

  8. Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression.

    Science.gov (United States)

    Zhu, Xi; Helpman, Liat; Papini, Santiago; Schneier, Franklin; Markowitz, John C; Van Meter, Page E; Lindquist, Martin A; Wager, Tor D; Neria, Yuval

    2017-07-01

    Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD-MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD-MDD is associated with different network connectivity abnormalities than PTSD alone. We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs-FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD-alone (n = 27), PTSD-MDD (n = 21), and trauma-exposed healthy controls (TEHCs, n = 34). Based on previous research, seeds included basolateral amygdala (BLA), centromedial amygdala (CMA), and nucleus accumbens (NAcc). Regardless of MDD comorbidity, PTSD was associated with decreased connectivity of BLA-orbitalfrontal cortex (OFC) and CMA-thalamus pathways, key to fear processing, and fear expression, respectively. PTSD-MDD, compared to PTSD-alone and TEHC, was associated with decreased connectivity across multiple amygdala and striatal-subcortical pathways: BLA-OFC, NAcc-thalamus, and NAcc-hippocampus. Further, while both the BLA-OFC and the NAcc-thalamus pathways were correlated with MDD symptoms, PTSD symptoms correlated with the amygdala pathways (BLA-OFC; CMA-thalamus) only. Comorbid PTSD-MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed. © 2016 Wiley Periodicals, Inc.

  9. Altered expression pattern of molecular factors involved in colonic smooth muscle functions: an immunohistochemical study in patients with diverticular disease.

    Science.gov (United States)

    Mattii, Letizia; Ippolito, Chiara; Segnani, Cristina; Battolla, Barbara; Colucci, Rocchina; Dolfi, Amelio; Bassotti, Gabrio; Blandizzi, Corrado; Bernardini, Nunzia

    2013-01-01

    The pathogenesis of diverticular disease (DD) is thought to result from complex interactions among dietary habits, genetic factors and coexistence of other bowel abnormalities. These conditions lead to alterations in colonic pressure and motility, facilitating the formation of diverticula. Although electrophysiological studies on smooth muscle cells (SMCs) have investigated colonic motor dysfunctions, scarce attention has been paid to their molecular abnormalities, and data on SMCs in DD are lacking. Accordingly, the main purpose of this study was to evaluate the expression patterns of molecular factors involved in the contractile functions of SMCs in the tunica muscularis of colonic specimens from patients with DD. By means of immunohistochemistry and image analysis, we examined the expression of Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs, as well as pS368-Cx43, PKCps, RhoA and αSMA, all known to regulate the functions of gap junctions and the contractile activity of SMCs. The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors. This study demonstrates, for the first time, that an altered pattern of factors involved in SMC contractility is present at level of the tunica muscularis of DD patients. Moreover, considering that our analysis was conducted on colonic tissues not directly affected by diverticular lesions or inflammatory reactions, it is conceivable that these molecular alterations may precede and predispose to the formation of diverticula, rather than being mere consequences of the disease.

  10. Global climate change--The technology challenge: China

    Science.gov (United States)

    Population growth and developmental pressures, spawned by an increasing demand for resource intensive goods, foods and services, are altering the planet in ways that threaten the long-term well-being of humans and other species. Global climate change and its associated impacts is...

  11. A lake classification concept for a more accurate global estimate of the dissolved inorganic carbon export from terrestrial ecosystems to inland waters

    Science.gov (United States)

    Engel, Fabian; Farrell, Kaitlin J.; McCullough, Ian M.; Scordo, Facundo; Denfeld, Blaize A.; Dugan, Hilary A.; de Eyto, Elvira; Hanson, Paul C.; McClure, Ryan P.; Nõges, Peeter; Nõges, Tiina; Ryder, Elizabeth; Weathers, Kathleen C.; Weyhenmeyer, Gesa A.

    2018-04-01

    The magnitude of lateral dissolved inorganic carbon (DIC) export from terrestrial ecosystems to inland waters strongly influences the estimate of the global terrestrial carbon dioxide (CO2) sink. At present, no reliable number of this export is available, and the few studies estimating the lateral DIC export assume that all lakes on Earth function similarly. However, lakes can function along a continuum from passive carbon transporters (passive open channels) to highly active carbon transformers with efficient in-lake CO2 production and loss. We developed and applied a conceptual model to demonstrate how the assumed function of lakes in carbon cycling can affect calculations of the global lateral DIC export from terrestrial ecosystems to inland waters. Using global data on in-lake CO2 production by mineralization as well as CO2 loss by emission, primary production, and carbonate precipitation in lakes, we estimated that the global lateral DIC export can lie within the range of {0.70}_{-0.31}^{+0.27} to {1.52}_{-0.90}^{+1.09} Pg C yr-1 depending on the assumed function of lakes. Thus, the considered lake function has a large effect on the calculated lateral DIC export from terrestrial ecosystems to inland waters. We conclude that more robust estimates of CO2 sinks and sources will require the classification of lakes into their predominant function. This functional lake classification concept becomes particularly important for the estimation of future CO2 sinks and sources, since in-lake carbon transformation is predicted to be altered with climate change.

  12. Network organization is globally atypical in autism: A graph theory study of intrinsic functional connectivity.

    Science.gov (United States)

    Keown, Christopher L; Datko, Michael C; Chen, Colleen P; Maximo, José Omar; Jahedi, Afrooz; Müller, Ralph-Axel

    2017-01-01

    Despite abundant evidence of brain network anomalies in autism spectrum disorder (ASD), findings have varied from broad functional underconnectivity to broad overconnectivity. Rather than pursuing overly simplifying general hypotheses ('under' vs. 'over'), we tested the hypothesis of atypical network distribution in ASD (i.e., participation of unusual loci in distributed functional networks). We used a selective high-quality data subset from the ABIDE datashare (including 111 ASD and 174 typically developing [TD] participants) and several graph theory metrics. Resting state functional MRI data were preprocessed and analyzed for detection of low-frequency intrinsic signal correlations. Groups were tightly matched for available demographics and head motion. As hypothesized, the Rand Index (reflecting how similar network organization was to a normative set of networks) was significantly lower in ASD than TD participants. This was accounted for by globally reduced cohesion and density, but increased dispersion of networks. While differences in hub architecture did not survive correction, rich club connectivity (among the hubs) was increased in the ASD group. Our findings support the model of reduced network integration (connectivity with networks) and differentiation (or segregation; based on connectivity outside network boundaries) in ASD. While the findings applied at the global level, they were not equally robust across all networks and in one case (greater cohesion within ventral attention network in ASD) even reversed.

  13. Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation.

    Directory of Open Access Journals (Sweden)

    Jean-François Gautier

    Full Text Available Fetal exposure to hyperglycemia impacts negatively kidney development and function.Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring.Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D (case group were matched with 28 offspring of T1D fathers (control group for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium. In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR and Effective Renal Plasma Flow (ERPF at baseline and during vasodilatation produced by amino acid infusion.Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1--a key enzyme involved in gene expression during early development--was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls.Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function.

  14. Polyhedral Lyapunov functions structurally ensure global asymptotic stability of dynamical networks iff the Jacobian is non-singular

    NARCIS (Netherlands)

    Blanchini, Franco; Giordano, G.

    2017-01-01

    For a vast class of dynamical networks, including chemical reaction networks (CRNs) with monotonic reaction rates, the existence of a polyhedral Lyapunov function (PLF) implies structural (i.e., parameter-free) local stability. Global structural stability is ensured under the additional

  15. NASA: Black soot fuels global warming

    CERN Multimedia

    2003-01-01

    New research from NASA's Goddard Space Center scientists suggests emissions of black soot have been altering the way sunlight reflects off Earth's snow. The research indicates the soot could be responsible for as much as 25 percent of global warming over the past century (assorted news items, 1 paragraph each).

  16. Local and global processing of music in high-functioning persons with autism: beyond central coherence?

    Science.gov (United States)

    Mottron, L; Peretz, I; Ménard, E

    2000-11-01

    A multi-modal abnormality in the integration of parts and whole has been proposed to account for a bias toward local stimuli in individuals with autism (Frith, 1989; Mottron & Belleville, 1993). In the current experiment, we examined the utility of hierarchical models in characterising musical information processing in autistic individuals. Participants were 13 high-functioning individuals with autism and 13 individuals of normal intelligence matched on chronological age, nonverbal IQ, and laterality, and without musical experience. The task consisted of same-different judgements of pairs of melodies. Differential local and global processing was assessed by manipulating the level, local or global, at which modifications occurred. No deficit was found in the two measures of global processing. In contrast, the clinical group performed better than the comparison group in the detection of change in nontransposed, contour-preserved melodies that tap local processing. These findings confirm the existence of a "local bias" in music perception in individuals with autism, but challenge the notion that it is accounted for by a deficit in global music processing. The present study suggests that enhanced processing of elementary physical properties of incoming stimuli, as found previously in the visual modality, may also exist in the auditory modality.

  17. Altered sensorimotor activation patterns in idiopathic dystonia-an activation likelihood estimation meta-analysis of functional brain imaging studies

    DEFF Research Database (Denmark)

    Løkkegaard, Annemette; Herz, Damian M; Haagensen, Brian Numelin

    2016-01-01

    Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements or postures. Functional neuroimaging studies have yielded abnormal task-related sensorimotor activation in dystonia, but the results appear to be rather variable across studies....... Further, study size was usually small including different types of dystonia. Here we performed an activation likelihood estimation (ALE) meta-analysis of functional neuroimaging studies in patients with primary dystonia to test for convergence of dystonia-related alterations in task-related activity...... postcentral gyrus, right superior temporal gyrus and dorsal midbrain. Apart from the midbrain cluster, all between-group differences in task-related activity were retrieved in a sub-analysis including only the 14 studies on patients with focal dystonia. For focal dystonia, an additional cluster of increased...

  18. Alterations in emotion generation and regulation neurocircuitry in depression and eating disorders: A comparative review of structural and functional neuroimaging studies.

    Science.gov (United States)

    Donofry, Shannon D; Roecklein, Kathryn A; Wildes, Jennifer E; Miller, Megan A; Erickson, Kirk I

    2016-09-01

    Major depression and eating disorders (EDs) are highly co-morbid and may share liability. Impaired emotion regulation may represent a common etiological or maintaining mechanism. Research has demonstrated that depressed individuals and individuals with EDs exhibit impaired emotion regulation, with these impairments being associated with changes in brain structure and function. The goal of this review was to evaluate findings from neuroimaging studies of depression and EDs to determine whether there are overlapping alterations in the brain regions known to be involved in emotion regulation, evidence of which would aid in the diagnosis and treatment of these conditions. Our review of the literature suggests that depression and EDs exhibit common structural and functional alterations in brain regions involved in emotion regulation, including the amygdala, ventral striatum and nucleus accumbens, anterior cingulate cortex, insula, and dorsolateral prefrontal cortex. We present preliminary support for a shared etiological mechanism. Future studies should consider manipulating emotion regulation in a sample of individuals with depression and EDs to better characterize abnormalities in these brain circuits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. A Direct Search Algorithm for Global Optimization

    Directory of Open Access Journals (Sweden)

    Enrique Baeyens

    2016-06-01

    Full Text Available A direct search algorithm is proposed for minimizing an arbitrary real valued function. The algorithm uses a new function transformation and three simplex-based operations. The function transformation provides global exploration features, while the simplex-based operations guarantees the termination of the algorithm and provides global convergence to a stationary point if the cost function is differentiable and its gradient is Lipschitz continuous. The algorithm’s performance has been extensively tested using benchmark functions and compared to some well-known global optimization algorithms. The results of the computational study show that the algorithm combines both simplicity and efficiency and is competitive with the heuristics-based strategies presently used for global optimization.

  20. A generalized quantitative antibody homeostasis model: maintenance of global antibody equilibrium by effector functions.

    Science.gov (United States)

    Prechl, József

    2017-11-01

    The homeostasis of antibodies can be characterized as a balanced production, target-binding and receptor-mediated elimination regulated by an interaction network, which controls B-cell development and selection. Recently, we proposed a quantitative model to describe how the concentration and affinity of interacting partners generates a network. Here we argue that this physical, quantitative approach can be extended for the interpretation of effector functions of antibodies. We define global antibody equilibrium as the zone of molar equivalence of free antibody, free antigen and immune complex concentrations and of dissociation constant of apparent affinity: [Ab]=[Ag]=[AbAg]= K D . This zone corresponds to the biologically relevant K D range of reversible interactions. We show that thermodynamic and kinetic properties of antibody-antigen interactions correlate with immunological functions. The formation of stable, long-lived immune complexes correspond to a decrease of entropy and is a prerequisite for the generation of higher-order complexes. As the energy of formation of complexes increases, we observe a gradual shift from silent clearance to inflammatory reactions. These rules can also be applied to complement activation-related immune effector processes, linking the physicochemical principles of innate and adaptive humoral responses. Affinity of the receptors mediating effector functions shows a wide range of affinities, allowing the continuous sampling of antibody-bound antigen over the complete range of concentrations. The generation of multivalent, multicomponent complexes triggers effector functions by crosslinking these receptors on effector cells with increasing enzymatic degradation potential. Thus, antibody homeostasis is a thermodynamic system with complex network properties, nested into the host organism by proper immunoregulatory and effector pathways. Maintenance of global antibody equilibrium is achieved by innate qualitative signals modulating a

  1. Chronic radiation-induced leukemogenesis: alterations of hematopoietic progenitor repair functions during preclinical phases

    International Nuclear Information System (INIS)

    Seed, T.M.; Kaspar, L.V.; Grdina, D.J.; Frazier, M.E.

    1987-01-01

    Chronic exposure to low daily doses of whole-body gamma irradiation elicits a high incidence of myeloid leukemia (ML) and related myeloproliferative diseases (MPD) in beagles. Previously, the authors identified and partially characterized a four-phase sequence of evolving MPD as a consequence of chronic radiation exposure. With a focus on preclinical alterations in granulocyte/monocyte-committed stem cells, they have identified two critical events in the process: (i) an early event, involving the coupling of acquired radioresistance of the stem cell with renewed proliferative capacity; and (ii) a late event, involving acquired autocrine functions and associated change in stem cell clonality. In terms of the early event, repair-associated parameters are currently being examined on the cellular level by both split-dose and low dose-rate-type assays with survival enhancement used as the measured end point. On the molecular level, these parameters are examined by microfluorometric alkaline elution assays with DNA damage and repair used as end points

  2. Reductions in soil surface albedo as a function of biochar application rate: implications for global radiative forcing

    International Nuclear Information System (INIS)

    Verheijen, Frank G A; Bastos, Ana Catarina; Keizer, Jan Jacob; Jeffery, Simon; Van der Velde, Marijn; Penížek, Vít; Beland, Martin

    2013-01-01

    Biochar can be defined as pyrolysed (charred) biomass produced for application to soils with the aim of mitigating global climate change while improving soil functions. Sustainable biochar application to soils has been estimated to reduce global greenhouse gas emissions by 71–130 Pg CO 2 -C e over 100 years, indicating an important potential to mitigate climate change. However, these estimates ignored changes in soil surface reflection by the application of dark-coloured biochar. Through a laboratory experiment we show a strong tendency for soil surface albedo to decrease as a power decay function with increasing biochar application rate, depending on soil moisture content, biochar application method and land use. Surface application of biochar resulted in strong reductions in soil surface albedo even at relatively low application rates. As a first assessment of the implications for climate change mitigation of these biochar–albedo relationships, we applied a first order global energy balance model to compare negative radiative forcings (from avoided CO 2 emissions) with positive radiative forcings (from reduced soil surface albedos). For a global-scale biochar application equivalent to 120 t ha −1 , we obtained reductions in negative radiative forcings of 5 and 11% for croplands and 11 and 23% for grasslands, when incorporating biochar into the topsoil or applying it to the soil surface, respectively. For a lower global biochar application rate (equivalent to 10 t ha −1 ), these reductions amounted to 13 and 44% for croplands and 28 and 94% for grasslands. Thus, our findings revealed the importance of including changes in soil surface albedo in studies assessing the net climate change mitigation potential of biochar, and we discuss the urgent need for field studies and more detailed spatiotemporal modelling. (letter)

  3. The helical ventricular myocardial band: global, three-dimensional, functional architecture of the ventricular myocardium.

    Science.gov (United States)

    Kocica, Mladen J; Corno, Antonio F; Carreras-Costa, Francesc; Ballester-Rodes, Manel; Moghbel, Mark C; Cueva, Clotario N C; Lackovic, Vesna; Kanjuh, Vladimir I; Torrent-Guasp, Francisco

    2006-04-01

    We are currently witnessing the advent of new diagnostic tools and therapies for heart diseases, but, without serious scientific consensus on fundamental questions about normal and diseased heart structure and function. During the last decade, three successive, international, multidisciplinary symposia were organized in order to setup fundamental research principles, which would allow us to make a significant step forward in understanding heart structure and function. Helical ventricular myocardial band of Torrent-Guasp is the revolutionary new concept in understanding global, three-dimensional, functional architecture of the ventricular myocardium. This concept defines the principal, cumulative vectors, integrating the tissue architecture (i.e. form) and net forces developed (i.e. function) within the ventricular mass. Here we expose the compendium of Torrent-Guasp's half-century long functional anatomical investigations in the light of ongoing efforts to define the integrative approach, which would lead to new understanding of the ventricular form and function by linking across multiple scales of biological organization, as defined in ongoing Physiome project. Helical ventricular myocardial band of Torrent-Guasp may also, hopefully, allow overcoming some difficulties encountered in contemporary efforts to create a comprehensive mathematical model of the heart.

  4. Altered Functional Connectivity of the Default Mode Network in Patients With Schizo-obsessive Comorbidity: A Comparison Between Schizophrenia and Obsessive-compulsive Disorder

    DEFF Research Database (Denmark)

    Wang, Yongming; Zou, Lai-quan; Xie, Wen-lan

    2018-01-01

    increased rsFC between subregions of the DMN and the middle temporal gyrus, but the OCD group exhibited decreased rsFC between them. These findings highlight a specific alteration in functional connectivity in the DMN in patients with SOC, and provide new insights into the dysfunctional brain organization...

  5. Alteration of intestinal barrier function during activity-based anorexia in mice.

    Science.gov (United States)

    Jésus, Pierre; Ouelaa, Wassila; François, Marie; Riachy, Lina; Guérin, Charlène; Aziz, Moutaz; Do Rego, Jean-Claude; Déchelotte, Pierre; Fetissov, Sergueï O; Coëffier, Moïse

    2014-12-01

    Anorexia nervosa is a severe eating disorder often leading to malnutrition and cachexia, but its pathophysiology is still poorly defined. Chronic food restriction during anorexia nervosa may induce gut barrier dysfunction, which may contribute to disease development and its complications. Here we have characterized intestinal barrier function in mice with activity-based anorexia (ABA), an animal model of anorexia nervosa. Male C57Bl/6 ABA or limited food access (LFA) mice were placed respectively in cages with or without activity wheel. After 5 days of acclimatization, both ABA and LFA mice had progressively limited access to food from 6 h/d at day 6 to 3 h/d at day 9 and until the end of experiment at day 17. A group of pair-fed mice (PF) was also compared to ABA. On day 17, food intake was lower in ABA than LFA mice (2.0 ± 0.18 g vs. 3.0 ± 0.14 g, p anorexia nervosa. The role of these alterations in the pathophysiology of anorexia nervosa should be further evaluated. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  6. Altered hypothalamic protein expression in a rat model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

  7. Needle puncture in rabbit functional spinal units alters rotational biomechanics.

    Science.gov (United States)

    Hartman, Robert A; Bell, Kevin M; Quan, Bichun; Nuzhao, Yao; Sowa, Gwendolyn A; Kang, James D

    2015-04-01

    An in vitro biomechanical study for rabbit lumbar functional spinal units (FSUs) using a robot-based spine testing system. To elucidate the effect of annular puncture with a 16 G needle on mechanical properties in flexion/extension, axial rotation, and lateral bending. Needle puncture of the intervertebral disk has been shown to alter mechanical properties of the disk in compression, torsion, and bending. The effect of needle puncture in FSUs, where intact spinal ligaments and facet joints may mitigate or amplify these changes in the disk, on spinal motion segment stability subject to physiological rotations remains unknown. Rabbit FSUs were tested using a robot testing system whose force/moment and position precision were assessed to demonstrate system capability. Flexibility testing methods were developed by load-to-failure testing in flexion/extension, axial rotation, and lateral bending. Subsequent testing methods were used to examine a 16 G needle disk puncture and No. 11 blade disk stab (positive control for mechanical disruption). Flexibility testing was used to assess segmental range-of-motion (degrees), neutral zone stiffness (N m/degrees) and width (degrees and N m), and elastic zone stiffness before and after annular injury. The robot-based system was capable of performing flexibility testing on FSUs-mean precision of force/moment measurements and robot system movements were elastic zone stiffness in flexion and lateral bending. These findings suggest that disk puncture and stab can destabilize FSUs in primary rotations.

  8. Altered structural covariance of the striatum in functional dyspepsia patients.

    Science.gov (United States)

    Liu, P; Zeng, F; Yang, F; Wang, J; Liu, X; Wang, Q; Zhou, G; Zhang, D; Zhu, M; Zhao, R; Wang, A; Gong, Q; Liang, F

    2014-08-01

    Functional dyspepsia (FD) is thought to be involved in dysregulation within the brain-gut axis. Recently, altered striatum activation has been reported in patients with FD. However, the gray matter (GM) volumes in the striatum and structural covariance patterns of this area are rarely explored. The purpose of this study was to examine the GM volumes and structural covariance patterns of the striatum between FD patients and healthy controls (HCs). T1-weighted magnetic resonance images were obtained from 44 FD patients and 39 HCs. Voxel-based morphometry (VBM) analysis was adopted to examine the GM volumes in the two groups. The caudate- or putamen-related regions identified from VBM analysis were then used as seeds to map the whole brain voxel-wise structural covariance patterns. Finally, a correlation analysis was used to investigate the effects of FD symptoms on the striatum. The results showed increased GM volumes in the bilateral putamen and right caudate. Compared with the structural covariance patterns of the HCs, the FD-related differences were mainly located in the amygdala, hippocampus/parahippocampus (HIPP/paraHIPP), thalamus, lingual gyrus, and cerebellum. And significant positive correlations were found between the volumes in the striatum and the FD duration in the patients. These findings provided preliminary evidence for GM changes in the striatum and different structural covariance patterns in patients with FD. The current results might expand our understanding of the pathophysiology of FD. © 2014 John Wiley & Sons Ltd.

  9. Knee posture during gait and global functioning post-stroke: a theoretical ICF framework using current measures in stroke rehabilitation

    OpenAIRE

    Neves Rosa, Marlene Cristina; Marques, Alda; Demain, Sara; Metcalf, Cheryl D.

    2015-01-01

    Purpose: To characterise the global functioning post-stroke in patients with normal knee posture (NKP) and abnormal knee posture (AKP) during loading-response. Methods: 35 people, 6 months post-stroke. with NKP and AKP were identified and assessed using clinical measures classified into the corresponding International Classification of Functioning, Disability and Health (ICF) domains: weight function (body mass index); muscle power (knee isometric strength); muscle tone (Modified Ashworth Sca...

  10. Inactivation of the Ecs ABC transporter of Staphylococcus aureus attenuates virulence by altering composition and function of bacterial wall.

    Directory of Open Access Journals (Sweden)

    Ing-Marie Jonsson

    2010-12-01

    Full Text Available Ecs is an ATP-binding cassette (ABC transporter present in aerobic and facultative anaerobic gram-positive Firmicutes. Inactivation of Bacillus subtilis Ecs causes pleiotropic changes in the bacterial phenotype including inhibition of intramembrane proteolysis. The molecule(s transported by Ecs is (are still unknown.In this study we mutated the ecsAB operon in two Staphylococcus aureus strains, Newman and LS-1. Phenotypic and functional characterization of these Ecs deficient mutants revealed a defect in growth, increased autolysis and lysostaphin sensitivity, altered composition of cell wall proteins including the precursor form of staphylokinase and an altered bacterial surface texture. DNA microarray analysis indicated that the Ecs deficiency changed expression of the virulence factor regulator protein Rot accompanied by differential expression of membrane transport proteins, particularly ABC transporters and phosphate-specific transport systems, protein A, adhesins and capsular polysaccharide biosynthesis proteins. Virulence of the ecs mutants was studied in a mouse model of hematogenous S. aureus infection. Mice inoculated with the ecs mutant strains developed markedly milder infections than those inoculated with the wild-type strains and had consequently lower mortality, less weight loss, milder arthritis and decreased persistence of staphylococci in the kidneys. The ecs mutants had higher susceptibility to ribosomal antibiotics and plant alkaloids chelerythrine and sanguinarine.Our results show that Ecs is essential for staphylococcal virulence and antimicrobial resistance probably since the transport function of Ecs is essential for the normal structure and function of the cell wall. Thus targeting Ecs may be a new approach in combating staphylococcal infection.

  11. Inactivation of the Ecs ABC transporter of Staphylococcus aureus attenuates virulence by altering composition and function of bacterial wall.

    Science.gov (United States)

    Jonsson, Ing-Marie; Juuti, Jarmo T; François, Patrice; AlMajidi, Rana; Pietiäinen, Milla; Girard, Myriam; Lindholm, Catharina; Saller, Manfred J; Driessen, Arnold J M; Kuusela, Pentti; Bokarewa, Maria; Schrenzel, Jacques; Kontinen, Vesa P

    2010-12-02

    Ecs is an ATP-binding cassette (ABC) transporter present in aerobic and facultative anaerobic gram-positive Firmicutes. Inactivation of Bacillus subtilis Ecs causes pleiotropic changes in the bacterial phenotype including inhibition of intramembrane proteolysis. The molecule(s) transported by Ecs is (are) still unknown. In this study we mutated the ecsAB operon in two Staphylococcus aureus strains, Newman and LS-1. Phenotypic and functional characterization of these Ecs deficient mutants revealed a defect in growth, increased autolysis and lysostaphin sensitivity, altered composition of cell wall proteins including the precursor form of staphylokinase and an altered bacterial surface texture. DNA microarray analysis indicated that the Ecs deficiency changed expression of the virulence factor regulator protein Rot accompanied by differential expression of membrane transport proteins, particularly ABC transporters and phosphate-specific transport systems, protein A, adhesins and capsular polysaccharide biosynthesis proteins. Virulence of the ecs mutants was studied in a mouse model of hematogenous S. aureus infection. Mice inoculated with the ecs mutant strains developed markedly milder infections than those inoculated with the wild-type strains and had consequently lower mortality, less weight loss, milder arthritis and decreased persistence of staphylococci in the kidneys. The ecs mutants had higher susceptibility to ribosomal antibiotics and plant alkaloids chelerythrine and sanguinarine. Our results show that Ecs is essential for staphylococcal virulence and antimicrobial resistance probably since the transport function of Ecs is essential for the normal structure and function of the cell wall. Thus targeting Ecs may be a new approach in combating staphylococcal infection.

  12. Altered dynamic functional connectivity in the default mode network in patients with cirrhosis and minimal hepatic encephalopathy

    International Nuclear Information System (INIS)

    Chen, Hua-Jun; Lin, Hai-Long; Chen, Qiu-Feng; Liu, Peng-Fei

    2017-01-01

    Abnormal brain intrinsic functional connectivity (FC) has been documented in minimal hepatic encephalopathy (MHE) by static connectivity analysis. However, changes in dynamic FC (dFC) remain unknown. We aimed to identify altered dFC within the default mode network (DMN) associated with MHE. Resting-state functional MRI data were acquired from 20 cirrhotic patients with MHE and 24 healthy controls. DMN seed regions were defined using seed-based FC analysis (centered on the posterior cingulate cortex (PCC)). Dynamic FC architecture was calculated using a sliding time-window method. K-means clustering (number of clusters = 2-4) was applied to estimate FC states. When the number of clusters was 2, MHE patients presented weaker connectivity strengths compared with controls in states 1 and 2. In state 1, decreased FC strength was found between the PCC/precuneus (PCUN) and right medial temporal lobe (MTL)/bilateral lateral temporal cortex (LTC); left inferior parietal lobule (IPL) and right MTL/left LTC; right IPL and right MTL/bilateral LTC; right MTL and right LTC; and medial prefrontal cortex (MPFC) and right MTL/bilateral LTC. In state 2, reduced FC strength was observed between the PCC/PCUN and bilateral MTL/bilateral LTC; left IPL and left MTL/bilateral LTC/MPFC; and left LTC and right LTC. Altered connectivities from state 1 were correlated with patient cognitive performance. Similar findings were observed when the number of clusters was set to 3 or 4. Aberrant dynamic DMN connectivity is an additional characteristic of MHE. Dynamic connectivity analysis offers a novel paradigm for understanding MHE-related mechanisms. (orig.)

  13. Altered dynamic functional connectivity in the default mode network in patients with cirrhosis and minimal hepatic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Hua-Jun; Lin, Hai-Long [Fujian Medical University Union Hospital, Department of Radiology, Fuzhou (China); Chen, Qiu-Feng; Liu, Peng-Fei [Central South University, School of Information Science and Engineering, Changsha (China)

    2017-09-15

    Abnormal brain intrinsic functional connectivity (FC) has been documented in minimal hepatic encephalopathy (MHE) by static connectivity analysis. However, changes in dynamic FC (dFC) remain unknown. We aimed to identify altered dFC within the default mode network (DMN) associated with MHE. Resting-state functional MRI data were acquired from 20 cirrhotic patients with MHE and 24 healthy controls. DMN seed regions were defined using seed-based FC analysis (centered on the posterior cingulate cortex (PCC)). Dynamic FC architecture was calculated using a sliding time-window method. K-means clustering (number of clusters = 2-4) was applied to estimate FC states. When the number of clusters was 2, MHE patients presented weaker connectivity strengths compared with controls in states 1 and 2. In state 1, decreased FC strength was found between the PCC/precuneus (PCUN) and right medial temporal lobe (MTL)/bilateral lateral temporal cortex (LTC); left inferior parietal lobule (IPL) and right MTL/left LTC; right IPL and right MTL/bilateral LTC; right MTL and right LTC; and medial prefrontal cortex (MPFC) and right MTL/bilateral LTC. In state 2, reduced FC strength was observed between the PCC/PCUN and bilateral MTL/bilateral LTC; left IPL and left MTL/bilateral LTC/MPFC; and left LTC and right LTC. Altered connectivities from state 1 were correlated with patient cognitive performance. Similar findings were observed when the number of clusters was set to 3 or 4. Aberrant dynamic DMN connectivity is an additional characteristic of MHE. Dynamic connectivity analysis offers a novel paradigm for understanding MHE-related mechanisms. (orig.)

  14. Perturbations of carotenoid and tetrapyrrole biosynthetic pathways result in differential alterations in chloroplast function and plastid signaling

    International Nuclear Information System (INIS)

    Park, Joon-Heum; Jung, Sunyo

    2017-01-01

    In this study, we used the biosynthetic inhibitors of carotenoid and tetrapyrrole biosynthetic pathways, norflurazon (NF) and oxyfluorfen (OF), as tools to gain insight into mechanisms of photooxidation in rice plants. NF resulted in bleaching symptom on leaves of the treated plants, whereas OF treatment developed a fast symptom of an apparent necrotic phenotype. Both plants exhibited decreases in photosynthetic efficiency, as indicated by F v /F m . NF caused severe disruption in thylakoid membranes, whereas OF-treated plants exhibited disruption of chloroplast envelope and plasma membrane. Levels of Lhca and Lhcb proteins in photosystem I (PSI) and PSII were reduced by photooxidative stress in NF- and OF-treated plants, with a greater decrease in NF plants. The down-regulation of nuclear-encoded photosynthesis genes Lhcb and rbcS was also found in both NF- and OF-treated plants, whereas plastid-encoded photosynthetic genes including RbcL, PsaC, and PsbD accumulated normally in NF plants but decreased drastically in OF plants. This proposes that the plastids in NF plants retain their potential to develop thylakoid membranes and that photobleaching is mainly controlled by nuclear genes. Distinct photooxidation patterns between NF- and OF-treated plants developed differential signaling, which might enable the plant to coordinate the expression of photosynthetic genes from the nuclear and plastidic genomes. - Highlights: • Two modes of photooxidation by carotenoid and tetrapyrrole biosynthetic inhibitors. • We examine differential alterations in chloroplast function and plastid signaling. • NF and OF cause differential alterations in chloroplast ultrastructure and function. • Photooxidation coordinates photosynthetic gene expression from nucleus and plastid.

  15. Cities, Networks, and Global Environmental Governance - Spaces of Innovation, Places of Leadership

    NARCIS (Netherlands)

    Bouteligier, S.

    2012-01-01

    As a result of global dynamics—the increasing interconnection of people and places—innovations in global environmental governance haved altered the role of cities in shaping the future of the planet. This book is a timely study of the importance of these social transformations in our increasingly

  16. Altered free radical metabolism in acute mountain sickness: implications for dynamic cerebral autoregulation and blood-brain barrier function

    DEFF Research Database (Denmark)

    Bailey, D M; Evans, K A; James, P E

    2008-01-01

    We tested the hypothesis that dynamic cerebral autoregulation (CA) and blood-brain barrier (BBB) function would be compromised in acute mountain sickness (AMS) subsequent to a hypoxia-mediated alteration in systemic free radical metabolism. Eighteen male lowlanders were examined in normoxia (21% O...... developed clinical AMS (AMS+) and were more hypoxaemic relative to subjects without AMS (AMS-). A more marked increase in the venous concentration of the ascorbate radical (A(*-)), lipid hydroperoxides (LOOH) and increased susceptibility of low-density lipoprotein (LDL) to oxidation was observed during...

  17. Uncertainty of Monetary Valued Ecosystem Services - Value Transfer Functions for Global Mapping.

    Directory of Open Access Journals (Sweden)

    Stefan Schmidt

    Full Text Available Growing demand of resources increases pressure on ecosystem services (ES and biodiversity. Monetary valuation of ES is frequently seen as a decision-support tool by providing explicit values for unconsidered, non-market goods and services. Here we present global value transfer functions by using a meta-analytic framework for the synthesis of 194 case studies capturing 839 monetary values of ES. For 12 ES the variance of monetary values could be explained with a subset of 93 study- and site-specific variables by utilizing boosted regression trees. This provides the first global quantification of uncertainties and transferability of monetary valuations. Models explain from 18% (water provision to 44% (food provision of variance and provide statistically reliable extrapolations for 70% (water provision to 91% (food provision of the terrestrial earth surface. Although the application of different valuation methods is a source of uncertainty, we found evidence that assuming homogeneity of ecosystems is a major error in value transfer function models. Food provision is positively correlated with better life domains and variables indicating positive conditions for human well-being. Water provision and recreation service show that weak ownerships affect valuation of other common goods negatively (e.g. non-privately owned forests. Furthermore, we found support for the shifting baseline hypothesis in valuing climate regulation. Ecological conditions and societal vulnerability determine valuation of extreme event prevention. Valuation of habitat services is negatively correlated with indicators characterizing less favorable areas. Our analysis represents a stepping stone to establish a standardized integration of and reporting on uncertainties for reliable and valid benefit transfer as an important component for decision support.

  18. Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism.

    Directory of Open Access Journals (Sweden)

    David John Kennaway

    Full Text Available The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight. Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured. Glucose, insulin and pyruvate tolerance tests were conducted and the expression of liver glycolytic and gluconeogenic enzyme mRNA determined. Bmal1 null mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 null male and female mice displayed increased adiposity (1.8 fold and 2.3 fold respectively on the normal diet, but the high fat diet did not exaggerate these differences. Despite normal glucose and insulin tolerance, Bmal1 null mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 null mice had arrhythmic clock gene expression in epigonadal fat and liver, and loss of rhythmic transcription of a range of metabolic genes. Furthermore, the expression of epigonadal fat Adipoq, Retn, Nampt, AdipoR1 and AdipoR2 and liver Pfkfb3 mRNA were down-regulated. These results show for the first time that global loss of Bmal1, and the consequent arrhythmicity, results in compensatory changes in adipokines involved in the cellular control of glucose metabolism.

  19. Selective alterations of NMDAR function and plasticity in D1 and D2 medium spiny neurons in the nucleus accumbens shell following chronic intermittent ethanol exposure.

    Science.gov (United States)

    Renteria, Rafael; Maier, Esther Y; Buske, Tavanna R; Morrisett, Richard A

    2017-01-01

    A major mouse model widely adopted in recent years to induce pronounced ethanol intake is the ethanol vapor model known as "CIE" or "Chronic Intermittent Ethanol." One critical question concerning this model is whether the rapid induction of high blood ethanol levels for such short time periods is sufficient to induce alterations in N-methyl-d-aspartate receptor (NMDAR) function which may contribute to excessive ethanol intake. In this study, we determined whether such short term intermittent ethanol exposure modulates NMDAR function as well as other prominent electrophysiological properties and the expression of plasticity in both D1 (D1+) and D2 (D1-) dopamine receptor expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell. To distinguish between the two subtypes of MSNs in the NAc we treated Drd1a-TdTomato transgenic mice with CIE vapor and electrophysiological recordings were conducted 24 h after the last vapor exposure. To investigate CIE induced alterations in plasticity, long-term depression (LTD) was induced by pairing low frequency stimulation (LFS) with post synaptic depolarization. In ethanol naïve mice, LFS induced synaptic depression (LTD) was apparent exclusively in D1+ MSNs. Whereas in slices prepared from CIE treated mice, LFS induced synaptic potentiation (LTP) in D1+ MSNs. Furthermore, following CIE exposure, LFS now produced LTD in D1- MSNs. We found that CIE exposure induced an increase in excitability in D1+ MSNs with no change in D1- MSNs. After CIE, we found a significant increase in spontaneous EPSCs (sEPSCs) frequency in D1+ but not D1- MSNs suggesting alterations in baseline α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) mediated signaling. CIE induced changes in NMDAR function were measured using the NMDA/AMPA ratio and input-output curves of isolated NMDAR currents. We observed a significant increase in NMDAR function in D1+ MSNs and a decrease in D1- MSNs after ethanol vapor exposure. The

  20. A global overview of drought and heat-induced tree mortality reveals emerging climate change risks for forests

    Science.gov (United States)

    Allen, Craig D.; Macalady, A.K.; Chenchouni, H.; Bachelet, D.; McDowell, N.; Vennetier, Michel; Kitzberger, T.; Rigling, A.; Breshears, D.D.; Hogg, E.H.(T.); Gonzalez, P.; Fensham, R.; Zhang, Z.; Castro, J.; Demidova, N.; Lim, J.-H.; Allard, G.; Running, S.W.; Semerci, A.; Cobb, N.

    2010-01-01

    Greenhouse gas emissions have significantly altered global climate, and will continue to do so in the future. Increases in the frequency, duration, and/or severity of drought and heat stress associated with climate change could fundamentally alter the composition, structure, and biogeography of forests in many regions. Of particular concern are potential increases in tree mortality associated with climate-induced physiological stress and interactions with other climate-mediated processes such as insect outbreaks and wildfire. Despite this risk, existing projections of tree mortality are based on models that lack functionally realistic mortality mechanisms, and there has been no attempt to track observations of climate-driven tree mortality globally. Here we present the first global assessment of recent tree mortality attributed to drought and heat stress. Although episodic mortality occurs in the absence of climate change, studies compiled here suggest that at least some of the world's forested ecosystems already may be responding to climate change and raise concern that forests may become increasingly vulnerable to higher background tree mortality rates and die-off in response to future warming and drought, even in environments that are not normally considered water-limited. This further suggests risks to ecosystem services, including the loss of sequestered forest carbon and associated atmospheric feedbacks. Our review also identifies key information gaps and scientific uncertainties that currently hinder our ability to predict tree mortality in response to climate change and emphasizes the need for a globally coordinated observation system. Overall, our review reveals the potential for amplified tree mortality due to drought and heat in forests worldwide.

  1. Cosmic microwave background constraints for global strings and global monopoles

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Eiguren, Asier; Lizarraga, Joanes; Urrestilla, Jon [Department of Theoretical Physics, University of the Basque Country UPV/EHU, 48080 Bilbao (Spain); Hindmarsh, Mark, E-mail: asier.lopez@ehu.eus, E-mail: joanes.lizarraga@ehu.eus, E-mail: m.b.hindmarsh@sussex.ac.uk, E-mail: jon.urrestilla@ehu.eus [Department of Physics and Astronomy, University of Sussex, Brighton, BN1 9QH (United Kingdom)

    2017-07-01

    We present the first cosmic microwave background (CMB) power spectra from numerical simulations of the global O( N ) linear σ-model, with N =2,3, which have global strings and monopoles as topological defects. In order to compute the CMB power spectra we compute the unequal time correlators (UETCs) of the energy-momentum tensor, showing that they fall off at high wave number faster than naive estimates based on the geometry of the defects, indicating non-trivial (anti-)correlations between the defects and the surrounding Goldstone boson field. We obtain source functions for Einstein-Boltzmann solvers from the UETCs, using a recently developed method that improves the modelling at the radiation-matter transition. We show that the interpolation function that mimics the transition is similar to other defect models, but not identical, confirming the non-universality of the interpolation function. The CMB power spectra for global strings and global monopoles have the same overall shape as those obtained using the non-linear σ-model approximation, which is well captured by a large- N calculation. However, the amplitudes are larger than the large- N calculation would naively predict, and in the case of global strings much larger: a factor of 20 at the peak. Finally we compare the CMB power spectra with the latest CMB data in other to put limits on the allowed contribution to the temperature power spectrum at multipole l = 10 of 1.7% for global strings and 2.4% for global monopoles. These limits correspond to symmetry-breaking scales of 2.9× 10{sup 15} GeV (6.3× 10{sup 14} GeV with the expected logarithmic scaling of the effective string tension between the simulation time and decoupling) and 6.4× 10{sup 15} GeV respectively. The bound on global strings is a significant one for the ultra-light axion scenario with axion masses m {sub a} ∼< 10{sup −28} eV . These upper limits indicate that gravitational waves from global topological defects will not be observable at

  2. Evaluation of bentonite alteration due to interactions with iron. Sensitivity analyses to identify the important factors for the bentonite alteration

    International Nuclear Information System (INIS)

    Sasamoto, Hiroshi; Wilson, James; Sato, Tsutomu

    2013-01-01

    Performance assessment of geological disposal systems for high-level radioactive waste requires a consideration of long-term systems behaviour. It is possible that the alteration of swelling clay present in bentonite buffers might have an impact on buffer functions. In the present study, iron (as a candidate overpack material)-bentonite (I-B) interactions were evaluated as the main buffer alteration scenario. Existing knowledge on alteration of bentonite during I-B interactions was first reviewed, then the evaluation methodology was developed considering modeling techniques previously used overseas. A conceptual model for smectite alteration during I-B interactions was produced. The following reactions and processes were selected: 1) release of Fe 2+ due to overpack corrosion; 2) diffusion of Fe 2+ in compacted bentonite; 3) sorption of Fe 2+ on smectite edge and ion exchange in interlayers; 4) dissolution of primary phases and formation of alteration products. Sensitivity analyses were performed to identify the most important factors for the alteration of bentonite by I-B interactions. (author)

  3. Satellite Global and Hemispheric Lower Tropospheric Temperature Annual Temperature Cycle

    Directory of Open Access Journals (Sweden)

    Michael A. Brunke

    2010-11-01

    Full Text Available Previous analyses of the Earth’s annual cycle and its trends have utilized surface temperature data sets. Here we introduce a new analysis of the global and hemispheric annual cycle using a satellite remote sensing derived data set during the period 1979–2009, as determined from the lower tropospheric (LT channel of the MSU satellite. While the surface annual cycle is tied directly to the heating and cooling of the land areas, the tropospheric annual cycle involves additionally the gain or loss of heat between the surface and atmosphere. The peak in the global tropospheric temperature in the 30 year period occurs on 10 July and the minimum on 9 February in response to the larger land mass in the Northern Hemisphere. The actual dates of the hemispheric maxima and minima are a complex function of many variables which can change from year to year thereby altering these dates.Here we examine the time of occurrence of the global and hemispheric maxima and minima lower tropospheric temperatures, the values of the annual maxima and minima, and the slopes and significance of the changes in these metrics.  The statistically significant trends are all relatively small. The values of the global annual maximum and minimum showed a small, but significant trend. Northern and Southern Hemisphere maxima and minima show a slight trend toward occurring later in the year. Most recent analyses of trends in the global annual cycle using observed surface data have indicated a trend toward earlier maxima and minima.

  4. Abnormal rich club organization and functional brain dynamics in schizophrenia.

    Science.gov (United States)

    van den Heuvel, Martijn P; Sporns, Olaf; Collin, Guusje; Scheewe, Thomas; Mandl, René C W; Cahn, Wiepke; Goñi, Joaquín; Hulshoff Pol, Hilleke E; Kahn, René S

    2013-08-01

    The human brain forms a large-scale structural network of regions and interregional pathways. Recent studies have reported the existence of a selective set of highly central and interconnected hub regions that may play a crucial role in the brain's integrative processes, together forming a central backbone for global brain communication. Abnormal brain connectivity may have a key role in the pathophysiology of schizophrenia. To examine the structure of the rich club in schizophrenia and its role in global functional brain dynamics. Structural diffusion tensor imaging and resting-state functional magnetic resonance imaging were performed in patients with schizophrenia and matched healthy controls. Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands. Forty-eight patients and 45 healthy controls participated in the study. An independent replication data set of 41 patients and 51 healthy controls was included to replicate and validate significant findings. MAIN OUTCOME(S) AND MEASURES: Measures of rich club organization, connectivity density of rich club connections and connections linking peripheral regions to brain hubs, measures of global brain network efficiency, and measures of coupling between brain structure and functional dynamics. Rich club organization between high-degree hub nodes was significantly affected in patients, together with a reduced density of rich club connections predominantly comprising the white matter pathways that link the midline frontal, parietal, and insular hub regions. This reduction in rich club density was found to be associated with lower levels of global communication capacity, a relationship that was absent for other white matter pathways. In addition, patients had an increase in the strength of structural connectivity-functional connectivity coupling. Our findings provide novel biological evidence that schizophrenia is characterized by a selective

  5. Altered neuronal excitability underlies impaired hippocampal function in an animal model of psychosis

    Directory of Open Access Journals (Sweden)

    Thomas eGrüter

    2015-05-01

    Full Text Available Psychosis is accompanied by severe attentional deficits, and impairments in associational-memory processing and sensory information processing that are ascribed to dysfunctions in prefrontal and hippocampal function. Disruptions of glutamatergic signalling may underlie these alterations: Antagonism of the N-methyl-D-aspartate receptor (NMDAR results in similar molecular, cellular, cognitive and behavioural changes in rodents and/or humans as those that occur in psychosis, raising the question as to whether changes in glutamatergic transmission may be intrinsic to the pathophysiology of the disease. In an animal model of psychosis that comprises treatment with the irreversible NMDAR-antagonist, MK801, we explored the cellular mechanisms that may underlie hippocampal dysfunction in psychosis. MK801-treatment resulted in a profound loss of hippocampal LTP that was evident 4 weeks after treatment. Whereas neuronal expression of the immediate early gene, Arc, was enhanced in the hippocampus by spatial learning in controls, MK801-treated animals failed to show activity-dependent increases in Arc expression. By contrast, a significant increase in basal Arc expression in the absence of learning was evident compared to controls. Paired-pulse facilitation was increased at the 40 ms interval indicating that NMDAR and/or fast GABAergic-mediated neurotransmission was disrupted. In line with this, MK801-treatment resulted in a significant decrease in GABA(A, and increase in GABA(B-receptor-expression in PFC, along with a significant increase of GABA(B- and NMDAR-GluN2B expression in the dentate gyrus. NMDAR-GluN1 or GluN2A subunit expression was unchanged. These data suggest that in psychosis, deficits in hippocampus-dependent memory may be caused by a loss of hippocampal LTP that arises through enhanced hippocampal neuronal excitability, altered GluN2B and GABA receptor expression and an uncoupling of the hippocampus-prefrontal cortex circuitry.

  6. SNPs altering ammonium transport activity of human Rhesus factors characterized by a yeast-based functional assay.

    Directory of Open Access Journals (Sweden)

    Aude Deschuyteneer

    Full Text Available Proteins of the conserved Mep-Amt-Rh family, including mammalian Rhesus factors, mediate transmembrane ammonium transport. Ammonium is an important nitrogen source for the biosynthesis of amino acids but is also a metabolic waste product. Its disposal in urine plays a critical role in the regulation of the acid/base homeostasis, especially with an acid diet, a trait of Western countries. Ammonium accumulation above a certain concentration is however pathologic, the cytotoxicity causing fatal cerebral paralysis in acute cases. Alteration in ammonium transport via human Rh proteins could have clinical outcomes. We used a yeast-based expression assay to characterize human Rh variants resulting from non synonymous single nucleotide polymorphisms (nsSNPs with known or unknown clinical phenotypes and assessed their ammonium transport efficiency, protein level, localization and potential trans-dominant impact. The HsRhAG variants (I61R, F65S associated to overhydrated hereditary stomatocytosis (OHSt, a disease affecting erythrocytes, proved affected in intrinsic bidirectional ammonium transport. Moreover, this study reveals that the R202C variant of HsRhCG, the orthologue of mouse MmRhcg required for optimal urinary ammonium excretion and blood pH control, shows an impaired inherent ammonium transport activity. Urinary ammonium excretion was RHcg gene-dose dependent in mouse, highlighting MmRhcg as a limiting factor. HsRhCG(R202C may confer susceptibility to disorders leading to metabolic acidosis for instance. Finally, the analogous R211C mutation in the yeast ScMep2 homologue also impaired intrinsic activity consistent with a conserved functional role of the preserved arginine residue. The yeast expression assay used here constitutes an inexpensive, fast and easy tool to screen nsSNPs reported by high throughput sequencing or individual cases for functional alterations in Rh factors revealing potential causal variants.

  7. Contribution of altered signal transduction associated to glutamate receptors in brain to the neurological alterations of hepatic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Vicente Felipo

    2006-01-01

    Patients with liver disease may present hepatic encephalopathy (HE), a complex neuropsychiatric syndrome covering a wide range of neurological alterations,including cognitive and motor disturbances. HE reduces the quality of life of the patients and is associated with poor prognosis. In the worse cases HE may lead to coma or death.The mechanisms leading to HE which are not well known are being studied using animal models. The neurological alterations in HE are a consequence of impaired cerebral function mainly due to alterations in neurotransmission. We review here some studies indicating that alterations in neurotransmission associated to different types of glutamate receptors are responsible for some of the cognitive and motor alterations present in HE.These studies show that the function of the signal transduction pathway glutamate-nitric oxide-cGMP associated to the NMDA type of glutamate receptors is impaired in brain in vivo in HE animal models as well as in brain of patients died of HE. Activation of NMDA receptors in brain activates this pathway and increases cGMP. In animal models of HE this increase in cGMP induced by activation of NMDA receptors is reduced,which is responsible for the impairment in learning ability in these animal models. Increasing cGMP by pharmacological means restores learning ability in rats with HE and may be a new therapeutic approach to improve cognitive function in patients with HE.However, it is necessary to previously assess the possible secondary effects.Patients with HE may present psychomotor slowing,hypokinesia and bradykinesia. Animal models of HE also show hypolocomotion. It has been shown in rats with HE that hypolocomotion is due to excessive activation of metabotropic glutamate receptors (mGluRs) in substantia nigra pars reticulata. Blocking mGluR1 in this brain area normalizes motor activity in the rats, suggesting that a similar treatment for patients with HE could be useful to treat psychomotor slowing and

  8. Global Human Footprint on the Linkage between Biodiversity and Ecosystem Functioning in Reef Fishes

    Science.gov (United States)

    Mora, Camilo; Aburto-Oropeza, Octavio; Ayala Bocos, Arturo; Ayotte, Paula M.; Banks, Stuart; Bauman, Andrew G.; Beger, Maria; Bessudo, Sandra; Booth, David J.; Brokovich, Eran; Brooks, Andrew; Chabanet, Pascale; Cinner, Joshua E.; Cortés, Jorge; Cruz-Motta, Juan J.; Cupul Magaña, Amilcar; DeMartini, Edward E.; Edgar, Graham J.; Feary, David A.; Ferse, Sebastian C. A.; Friedlander, Alan M.; Gaston, Kevin J.; Gough, Charlotte; Graham, Nicholas A. J.; Green, Alison; Guzman, Hector; Hardt, Marah; Kulbicki, Michel; Letourneur, Yves; López Pérez, Andres; Loreau, Michel; Loya, Yossi; Martinez, Camilo; Mascareñas-Osorio, Ismael; Morove, Tau; Nadon, Marc-Olivier; Nakamura, Yohei; Paredes, Gustavo; Polunin, Nicholas V. C.; Pratchett, Morgan S.; Reyes Bonilla, Héctor; Rivera, Fernando; Sala, Enric; Sandin, Stuart A.; Soler, German; Stuart-Smith, Rick; Tessier, Emmanuel; Tittensor, Derek P.; Tupper, Mark; Usseglio, Paolo; Vigliola, Laurent; Wantiez, Laurent; Williams, Ivor; Wilson, Shaun K.; Zapata, Fernando A.

    2011-01-01

    Difficulties in scaling up theoretical and experimental results have raised controversy over the consequences of biodiversity loss for the functioning of natural ecosystems. Using a global survey of reef fish assemblages, we show that in contrast to previous theoretical and experimental studies, ecosystem functioning (as measured by standing biomass) scales in a non-saturating manner with biodiversity (as measured by species and functional richness) in this ecosystem. Our field study also shows a significant and negative interaction between human population density and biodiversity on ecosystem functioning (i.e., for the same human density there were larger reductions in standing biomass at more diverse reefs). Human effects were found to be related to fishing, coastal development, and land use stressors, and currently affect over 75% of the world's coral reefs. Our results indicate that the consequences of biodiversity loss in coral reefs have been considerably underestimated based on existing knowledge and that reef fish assemblages, particularly the most diverse, are greatly vulnerable to the expansion and intensity of anthropogenic stressors in coastal areas. PMID:21483714

  9. Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.

    Directory of Open Access Journals (Sweden)

    Danny Gauvreau

    Full Text Available BACKGROUND: Obesity is considered as a systemic chronic low grade inflammation characterized by increased serum pro-inflammatory proteins and accumulation of macrophages within white adipose tissue (WAT of obese patients. C5L2, a 7-transmembrane receptor, serves a dual function, binding the lipogenic hormone acylation stimulating protein (ASP, and C5a, involved in innate immunity. AIM: We evaluated the impact of C5L2 on macrophage infiltration in WAT of wildtype (Ctl and C5L2 knock-out (C5L2(-/- mice over 6, 12 and 24 weeks on a chow diet and moderate diet-induced obesity (DIO conditions. RESULTS: In Ctl mice, WAT C5L2 and C5a receptor mRNA increased (up to 10-fold both over time and with DIO. By contrast, in C5L2(-/-, there was no change in C5aR in WAT. C5L2(-/- mice displayed higher macrophage content in WAT, varying by time, fat depot and diet, associated with altered systemic and WAT cytokine patterns compared to Ctl mice. However, in all cases, the M1 (pro- vs M2 (anti-inflammatory macrophage proportion was unchanged but C5L2(-/- adipose tissue secretome appeared to be more chemoattractant. Moreover, C5L2(-/- mice have increased food intake, increased WAT, and altered WAT lipid gene expression, which is reflected systemically. Furthermore, C5L2(-/- mice have altered glucose/insulin metabolism, adiponectin and insulin signalling gene expression in WAT, which could contribute to development of insulin resistance. CONCLUSION: Disruption of C5L2 increases macrophage presence in WAT, contributing to obesity-associated pathologies, and further supports a dual role of complement in WAT. Understanding this effect of the complement system pathway could contribute to targeting treatment of obesity and its comorbidities.

  10. Among Early Appearing Non-Motor Signs of Parkinson’s Disease, Alteration of Olfaction but Not Electroencephalographic Spectrum Correlates with Motor Function

    Directory of Open Access Journals (Sweden)

    Vitalii V. Cozac

    2017-10-01

    Full Text Available Olfactory decline is a frequent and early non-motor symptom in Parkinson’s disease (PD, which is increasingly used for diagnostic purposes. Another early appearing sign of PD consists in electroencephalographic (EEG alterations. The combination of olfactory and EEG assessment may improve the identification of patients with early stages of PD. We hypothesized that olfactory capacity would be correlated with EEG alterations and motor and cognitive impairment in PD patients. To the best of our knowledge, the mutual influence of both markers of PD—olfactory decrease and EEG changes—was not studied before. We assessed the function of odor identification using olfactory “Screening 12 Test” (“Sniffin’ Sticks®”, between two samples: patients with PD and healthy controls (HC. We analyzed correlations between the olfactory function and demographical parameters, Unified Parkinson’s Disease Rating Scale (UPDRS-III, cognitive task performance, and spectral alpha/theta ratio (α/θ. In addition, we used receiver operating characteristic-curve analysis to check the classification capacity (PD vs HC of olfactory function, α/θ, and a combined marker (olfaction and α/θ. Olfactory capacity was significantly decreased in PD patients, and correlated with age, disease duration, UPDRS-III, and with items of UPDRS-III related to gait and axial rigidity. In HC, olfaction correlated with age only. No correlation with α/θ was identified in both samples. Combined marker showed the largest area under the curve. In addition to EEG, the assessment of olfactory function may be a useful tool in the early characterization and follow-up of PD.

  11. Voxel Scale Complex Networks of Functional Connectivity in the Rat Brain: Neurochemical State Dependence of Global and Local Topological Properties

    Directory of Open Access Journals (Sweden)

    Adam J. Schwarz

    2012-01-01

    Full Text Available Network analysis of functional imaging data reveals emergent features of the brain as a function of its topological properties. However, the brain is not a homogeneous network, and the dependence of functional connectivity parameters on neuroanatomical substrate and parcellation scale is a key issue. Moreover, the extent to which these topological properties depend on underlying neurochemical changes remains unclear. In the present study, we investigated both global statistical properties and the local, voxel-scale distribution of connectivity parameters of the rat brain. Different neurotransmitter systems were stimulated by pharmacological challenge (d-amphetamine, fluoxetine, and nicotine to discriminate between stimulus-specific functional connectivity and more general features of the rat brain architecture. Although global connectivity parameters were similar, mapping of local connectivity parameters at high spatial resolution revealed strong neuroanatomical dependence of functional connectivity in the rat brain, with clear differentiation between the neocortex and older brain regions. Localized foci of high functional connectivity independent of drug challenge were found in the sensorimotor cortices, consistent with the high neuronal connectivity in these regions. Conversely, the topological properties and node roles in subcortical regions varied with neurochemical state and were dependent on the specific dynamics of the different functional processes elicited.

  12. Visual feedback alters force control and functional activity in the visuomotor network after stroke

    Directory of Open Access Journals (Sweden)

    Derek B. Archer

    2018-01-01

    Full Text Available Modulating visual feedback may be a viable option to improve motor function after stroke, but the neurophysiological basis for this improvement is not clear. Visual gain can be manipulated by increasing or decreasing the spatial amplitude of an error signal. Here, we combined a unilateral visually guided grip force task with functional MRI to understand how changes in the gain of visual feedback alter brain activity in the chronic phase after stroke. Analyses focused on brain activation when force was produced by the most impaired hand of the stroke group as compared to the non-dominant hand of the control group. Our experiment produced three novel results. First, gain-related improvements in force control were associated with an increase in activity in many regions within the visuomotor network in both the stroke and control groups. These regions include the extrastriate visual cortex, inferior parietal lobule, ventral premotor cortex, cerebellum, and supplementary motor area. Second, the stroke group showed gain-related increases in activity in additional regions of lobules VI and VIIb of the ipsilateral cerebellum. Third, relative to the control group, the stroke group showed increased activity in the ipsilateral primary motor cortex, and activity in this region did not vary as a function of visual feedback gain. The visuomotor network, cerebellum, and ipsilateral primary motor cortex have each been targeted in rehabilitation interventions after stroke. Our observations provide new insight into the role these regions play in processing visual gain during a precisely controlled visuomotor task in the chronic phase after stroke.

  13. CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

    International Nuclear Information System (INIS)

    Horton, Megan K.; Blount, Benjamin C.; Valentin-Blasini, Liza; Wapner, Ronald; Whyatt, Robin; Gennings, Chris; Factor-Litvak, Pam

    2015-01-01

    Background: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy Objectives: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. Methods: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4–0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. - Highlights: • Perchlorate, nitrate, thiocyanate and iodide measured in maternal urine. • Thyroid function (TSH and Free T4) measured in maternal blood

  14. CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

    Energy Technology Data Exchange (ETDEWEB)

    Horton, Megan K., E-mail: megan.horton@mssm.edu [Department of Preventive Medicine, Icahn School of Medicine, New York, New York (United States); Blount, Benjamin C.; Valentin-Blasini, Liza [National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia (United States); Wapner, Ronald [Department of Obstetrics and Gynecology, Columbia University, New York, New York (United States); Whyatt, Robin [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York (United States); Gennings, Chris [Department of Preventive Medicine, Icahn School of Medicine, New York, New York (United States); Factor-Litvak, Pam [Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York (United States)

    2015-11-15

    Background: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy Objectives: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. Methods: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4–0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. - Highlights: • Perchlorate, nitrate, thiocyanate and iodide measured in maternal urine. • Thyroid function (TSH and Free T4) measured in maternal blood

  15. Alteration of plant meristem function by manipulation of the Retinoblastoma-like plant RRB gene

    Science.gov (United States)

    Durfee, Tim [Madison, WI; Feiler, Heidi [Albany, CA; Gruissem, Wilhelm [Forch, CH; Jenkins, Susan [Martinez, CA; Roe, Judith [Manhattan, KS; Zambryski, Patricia [Berkeley, CA

    2007-01-16

    This invention provides methods and compositions for altering the growth, organization, and differentiation of plant tissues. The invention is based on the discovery that, in plants, genetically altering the levels of Retinoblastoma-related gene (RRB) activity produces dramatic effects on the growth, proliferation, organization, and differentiation of plant meristem.

  16. From City-States to Global Cities: the role of Cities in Global Governance

    Directory of Open Access Journals (Sweden)

    Domingos Martins Vaz

    2017-11-01

    Full Text Available Global governance has altered institutional architecture and the systemic and institutional conditions under which power is exercised, as well as the characteristics of the political system, the form of government, and the system of intermediation of interests. However, although it has surpassed the State’s dimension of power, it created new interstate dimensions and new relations between powers, particularly at the level of cities. Cities have helped to solve common problems in a more efficient and effective way by facilitating the exchange of knowledge, sharing of solutions and resources, and building capacity to implement and monitor progress in order to achieve collectively agreed goals, in a bottom-up approach. Cities have the virtue of securing the most direct social and political contract between societies and the notion of authority. This study, therefore, aims to reflect on this emerging, less hierarchical and rigid governance and address complex global challenges such as climate and demographic change; increasing crime rates; disruptive technology; and pressures on resources, infrastructure and energy. As a global/local interface, cities can ensure effective solutions to current challenges and act together in areas where the global agenda has stalled.

  17. Alteration of Fatty-Acid-Metabolizing Enzymes Affects Mitochondrial Form and Function in Hereditary Spastic Paraplegia

    Science.gov (United States)

    Tesson, Christelle; Nawara, Magdalena; Salih, Mustafa A.M.; Rossignol, Rodrigue; Zaki, Maha S.; Al Balwi, Mohammed; Schule, Rebecca; Mignot, Cyril; Obre, Emilie; Bouhouche, Ahmed; Santorelli, Filippo M.; Durand, Christelle M.; Oteyza, Andrés Caballero; El-Hachimi, Khalid H.; Al Drees, Abdulmajeed; Bouslam, Naima; Lamari, Foudil; Elmalik, Salah A.; Kabiraj, Mohammad M.; Seidahmed, Mohammed Z.; Esteves, Typhaine; Gaussen, Marion; Monin, Marie-Lorraine; Gyapay, Gabor; Lechner, Doris; Gonzalez, Michael; Depienne, Christel; Mochel, Fanny; Lavie, Julie; Schols, Ludger; Lacombe, Didier; Yahyaoui, Mohamed; Al Abdulkareem, Ibrahim; Zuchner, Stephan; Yamashita, Atsushi; Benomar, Ali; Goizet, Cyril; Durr, Alexandra; Gleeson, Joseph G.; Darios, Frederic; Brice, Alexis; Stevanin, Giovanni

    2012-01-01

    Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function. PMID:23176821

  18. Altered Potassium Ion Channel Function as a Possible Mechanism of Increased Blood Pressure in Rats Fed Thermally Oxidized Palm Oil Diets.

    Science.gov (United States)

    Nkanu, Etah E; Owu, Daniel U; Osim, Eme E

    2017-12-27

    Intake of thermally oxidized palm oil leads to cytotoxicity and alteration of the potassium ion channel function. This study investigated the effects of fresh and thermally oxidized palm oil diets on blood pressure and potassium ion channel function in blood pressure regulation. Male Wistar rats were randomly divided into three groups of eight rats. Control group received normal feed; fresh palm oil (FPO) and thermally oxidized palm oil (TPO) groups were fed a diet mixed with 15% (weight/weight) fresh palm oil and five times heated palm oil, respectively, for 16 weeks. Blood pressure was measured; blood samples, hearts, and aortas were collected for biochemical and histological analyses. Thermally oxidized palm oil significantly elevated basal mean arterial pressure (MAP). Glibenclamide (10 -5 mmol/L) and tetraethylammonium (TEA; 10 -3 mmol/L) significantly raised blood pressure in TPO compared with FPO and control groups. Levcromakalim (10 -6 mmol/L) significantly (p palm oil increases MAP probably due to the attenuation of adenosine triphosphate-sensitive potassium (K ATP ) and large-conductance calcium-dependent potassium (BK Ca ) channels, tissue peroxidation, and altered histological structures of the heart and blood vessels.

  19. SPM analysis and cognitive dysfunctions in patients with transient global amnesia

    International Nuclear Information System (INIS)

    Jeong, Young Jin; Kang, Do Young; Yun, Go Un; Park, Kyung Won; Kim, Jae Woo

    2004-01-01

    Transient global amnesia (TGA) is known as a disease of benign nature characterized with clinically transient global antegrade amnesia and a variable degree of global retrograde memory impairment, but it usually resolved within 24 hours. The aims of this study are to assess the alterations in regional cerebral blood flow (rCBF) by Tc-99m HMPAO SPECT imaging with statistical parametric mapping (SPM) analysis and to verify the cognitive deficits by neuropsychological test in TGA patients. Twelve patients with TGA and age-matched normal control subjects participated in this study. Tc-99m HMPAO SPECT was performed within 1 to 19 days (mean duration: 7.3:±5.2 days) after the events to measure the rCBF. SPECT images were analyzed using SPM (SPM99) with Matlab 5.3. Seoul Neuropsychological Screening Battery test was also done within 2 to 8 days (mean duration 3.8±2.2 days) for cognitive functions in 8 of 12 patients with TGA. The SPM analysis of SPECT images showed significantly decreased rCBF in the left inferior frontal gyrus (Brodmann area 9), the left supramarginal gyrus (Brodmann area 40), the left postcentral gyrus (Brodmann area 40) and the left precentral gyrus (Brodmann area 4) in patients with TGA (uncorrected p<0.01). Neuropsychological test findings represented that several cognitive functions. such as, verbal memory, visual memory, phonemic fluency and confrontational naming, were impaired in patients with TGA compared with normal control. Additionally, on SPM analysis, we found lesions of hyperperfusion in contralateral cerebral hemisphere. Our study shows perfusion deficits in the left cerebral hemisphere in patients with TGA and several cognitive dysfunctions. And we found after clinical symptoms were completely resolved, the lesions of hypoperfusion were still remained. We found that functional quantitative neuroimaging study and neuropsychological test are useful to understand underlying pathomachanism of TGA

  20. SPM analysis and cognitive dysfunctions in patients with transient global amnesia

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young Jin; Kang, Do Young; Yun, Go Un; Park, Kyung Won; Kim, Jae Woo [School of Medicine, Donga University, Busan (Korea, Republic of)

    2004-07-01

    Transient global amnesia (TGA) is known as a disease of benign nature characterized with clinically transient global antegrade amnesia and a variable degree of global retrograde memory impairment, but it usually resolved within 24 hours. The aims of this study are to assess the alterations in regional cerebral blood flow (rCBF) by Tc-99m HMPAO SPECT imaging with statistical parametric mapping (SPM) analysis and to verify the cognitive deficits by neuropsychological test in TGA patients. Twelve patients with TGA and age-matched normal control subjects participated in this study. Tc-99m HMPAO SPECT was performed within 1 to 19 days (mean duration: 7.3:{+-}5.2 days) after the events to measure the rCBF. SPECT images were analyzed using SPM (SPM99) with Matlab 5.3. Seoul Neuropsychological Screening Battery test was also done within 2 to 8 days (mean duration 3.8{+-}2.2 days) for cognitive functions in 8 of 12 patients with TGA. The SPM analysis of SPECT images showed significantly decreased rCBF in the left inferior frontal gyrus (Brodmann area 9), the left supramarginal gyrus (Brodmann area 40), the left postcentral gyrus (Brodmann area 40) and the left precentral gyrus (Brodmann area 4) in patients with TGA (uncorrected p<0.01). Neuropsychological test findings represented that several cognitive functions. such as, verbal memory, visual memory, phonemic fluency and confrontational naming, were impaired in patients with TGA compared with normal control. Additionally, on SPM analysis, we found lesions of hyperperfusion in contralateral cerebral hemisphere. Our study shows perfusion deficits in the left cerebral hemisphere in patients with TGA and several cognitive dysfunctions. And we found after clinical symptoms were completely resolved, the lesions of hypoperfusion were still remained. We found that functional quantitative neuroimaging study and neuropsychological test are useful to understand underlying pathomachanism of TGA.

  1. A global view of structure-function relationships in the tautomerase superfamily.

    Science.gov (United States)

    Davidson, Rebecca; Baas, Bert-Jan; Akiva, Eyal; Holliday, Gemma L; Polacco, Benjamin J; LeVieux, Jake A; Pullara, Collin R; Zhang, Yan Jessie; Whitman, Christian P; Babbitt, Patricia C

    2018-02-16

    The tautomerase superfamily (TSF) consists of more than 11,000 nonredundant sequences present throughout the biosphere. Characterized members have attracted much attention because of the unusual and key catalytic role of an N-terminal proline. These few characterized members catalyze a diverse range of chemical reactions, but the full scale of their chemical capabilities and biological functions remains unknown. To gain new insight into TSF structure-function relationships, we performed a global analysis of similarities across the entire superfamily and computed a sequence similarity network to guide classification into distinct subgroups. Our results indicate that TSF members are found in all domains of life, with most being present in bacteria. The eukaryotic members of the cis -3-chloroacrylic acid dehalogenase subgroup are limited to fungal species, whereas the macrophage migration inhibitory factor subgroup has wide eukaryotic representation (including mammals). Unexpectedly, we found that 346 TSF sequences lack Pro-1, of which 85% are present in the malonate semialdehyde decarboxylase subgroup. The computed network also enabled the identification of similarity paths, namely sequences that link functionally diverse subgroups and exhibit transitional structural features that may help explain reaction divergence. A structure-guided comparison of these linker proteins identified conserved transitions between them, and kinetic analysis paralleled these observations. Phylogenetic reconstruction of the linker set was consistent with these findings. Our results also suggest that contemporary TSF members may have evolved from a short 4-oxalocrotonate tautomerase-like ancestor followed by gene duplication and fusion. Our new linker-guided strategy can be used to enrich the discovery of sequence/structure/function transitions in other enzyme superfamilies. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Globalization and Firm Competitiveness in the Middle East and North Africa Region

    OpenAIRE

    Fawzy, Samiha

    2002-01-01

    Globalization has increased competitive pressures on firms. Together with rapid technological change, it has altered the environment in which firms operate. While globalization offers unprecedented opportunities for firms to act successfully, it simultaneously heightens the risks for firms lagging behind. In an open and liberalized world, increasing firm competitiveness has become a major ...

  3. Abnormal rich club organization and impaired correlation between structural and functional connectivity in migraine sufferers.

    Science.gov (United States)

    Li, Kang; Liu, Lijun; Yin, Qin; Dun, Wanghuan; Xu, Xiaolin; Liu, Jixin; Zhang, Ming

    2017-04-01

    Because of the unique position of the topologically central role of densely interconnected brain hubs, our study aimed to investigate whether these regions and their related connections would be particularly vulnerable to migraine. In our study, we explored the rich club structure and its role in global functional dynamics in 30 patients with migraine without aura and 30 healthy controls. DTI and resting fMRI were used to construct structural connectivity (SC) and functional connectivity (FC) networks. An independent replication data set of 26 patients and 26 controls was included to replicate and validate significant findings. As compared with the controls, the structural networks of patients exhibited altered rich club organization with higher level of feeder connection density, abnormal small-world organization with increased global efficiency and decreased strength of SC-FC coupling. As these abnormal topological properties and headache attack duration exhibited a significant association with increased density of feeder connections, our results indicated that migraine may be characterized by a selective alteration of the structural connectivity of the rich club regions, tending to have higher 'bridgeness' with non-rich club regions, which may increase the integration among pain-related brain circuits with more excitability but less inhibition for the modulation of migraine.

  4. Alterations of Resting-State Static and Dynamic Functional Connectivity of the Dorsolateral Prefrontal Cortex in Subjects with Internet Gaming Disorder

    Directory of Open Access Journals (Sweden)

    Xu Han

    2018-02-01

    Full Text Available Internet gaming disorder (IGD, a major behavior disorder, has gained increasing attention. Recent studies indicate altered resting-state static functional connectivity (FC of the dorsolateral prefrontal cortex (DLPFC in subjects with IGD. Whereas static FC often provides information on functional changes in subjects with IGD, investigations of temporal changes in FC between the DLPFC and the other brain regions may shed light on the dynamic characteristics of brain function associated with IGD. Thirty subjects with IGD and 30 healthy controls (HCs matched for age, gender and education status were recruited. Using the bilateral DLPFC as seeds, static FC and dynamic FC maps were calculated and compared between groups. Correlations between alterations in static FC and dynamic FC and clinical variables were also investigated within the IGD group. The IGD group showed significantly lower static FC between the right DLPFC and the left rolandic operculum while higher static FC between the right DLPFC and the left pars triangularis when compared to HCs. The IGD group also had significantly decreased dynamic FC between the right DLPFC and the left insula, right putamen and left precentral gyrus, and increased dynamic FC in the left precuneus. Moreover, the dynamic FC between the right DLPFC and the left insula was negatively correlated with the severity of IGD. Dynamic FC can be used as a powerful supplement to static FC, helping us obtain a more comprehensive understanding of large-scale brain network activity in IGD and put forward new ideas for behavioral intervention therapy for it.

  5. Uncertainties of Predictions from Parton Distribution Functions 1, the Lagrange Multiplier Method

    CERN Document Server

    Stump, D R; Brock, R; Casey, D; Huston, J; Kalk, J; Lai, H L; Tung, W K

    2002-01-01

    We apply the Lagrange Multiplier method to study the uncertainties of physical predictions due to the uncertainties of parton distribution functions (PDFs), using the cross section for W production at a hadron collider as an archetypal example. An effective chi-squared function based on the CTEQ global QCD analysis is used to generate a series of PDFs, each of which represents the best fit to the global data for some specified value of the cross section. By analyzing the likelihood of these "alterative hypotheses", using available information on errors from the individual experiments, we estimate that the fractional uncertainty of the cross section due to current experimental input to the PDF analysis is approximately 4% at the Tevatron, and 10% at the LHC. We give sets of PDFs corresponding to these up and down variations of the cross section. We also present similar results on Z production at the colliders. Our method can be applied to any combination of physical variables in precision QCD phenomenology, an...

  6. Comparison of Visuospatial and Verbal Abilities in First Psychotic Episode of Schizophrenia Spectrum Disorder: Impact on Global Functioning and Quality of Life

    Czech Academy of Sciences Publication Activity Database

    Rodriquez, M.; Španiel, F.; Konrádová, L.; Sedláková, K.; Dvorská, K.; Prajsová, J.; Kratochvílová, Z.; Levčík, David; Vlček, Kamil; Fajnerová, Iveta

    2015-01-01

    Roč. 9, Dec 18 (2015), s. 322 ISSN 1662-5153 R&D Projects: GA MZd(CZ) NT13386 Institutional support: RVO:67985823 Keywords : cognitive deficit * first psychotic episode * schizophrenia spectrum disorder * global functioning * quality of life * visuospatial functions * verbal functions * antipsychotic medication Subject RIV: FH - Neurology Impact factor: 3.392, year: 2015

  7. CT14 intrinsic charm parton distribution functions from CTEQ-TEA global analysis

    Science.gov (United States)

    Hou, Tie-Jiun; Dulat, Sayipjamal; Gao, Jun; Guzzi, Marco; Huston, Joey; Nadolsky, Pavel; Schmidt, Carl; Winter, Jan; Xie, Keping; Yuan, C.-P.

    2018-02-01

    We investigate the possibility of a (sizable) nonperturbative contribution to the charm parton distribution function (PDF) in a nucleon, theoretical issues arising in its interpretation, and its potential impact on LHC scattering processes. The "fitted charm" PDF obtained in various QCD analyses contains a process-dependent component that is partly traced to power-suppressed radiative contributions in DIS and is generally different at the LHC. We discuss separation of the universal component of the nonperturbative charm from the rest of the radiative contributions and estimate its magnitude in the CT14 global QCD analysis at the next-to-next-to leading order in the QCD coupling strength, including the latest experimental data from HERA and the Large Hadron Collider. Models for the nonperturbative charm PDF are examined as a function of the charm quark mass and other parameters. The prospects for testing these models in the associated production of a Z boson and a charm jet at the LHC are studied under realistic assumptions, including effects of the final-state parton showering.

  8. Association between structural and functional brain alterations in drug-free patients with schizophrenia: a multimodal meta-analysis.

    Science.gov (United States)

    Gao, Xin; Zhang, Wenjing; Yao, Li; Xiao, Yuan; Liu, Lu; Liu, Jieke; Li, Siyi; Tao, Bo; Shah, Chandan; Gong, Qiyong; Sweeney, John A; Lui, Su

    2018-03-01

    Neuroimaging studies have shown both structural and functional abnormalities in patients with schizophrenia. Recently, studies have begun to explore the association between structural and functional grey matter abnormalities. By conducting a meta-analysis on morphometric and functional imaging studies of grey matter alterations in drug-free patients, the present study aims to examine the degree of overlap between brain regions with anatomic and functional changes in patients with schizophrenia. We performed a systematic search of PubMed, Embase, Web of Science and the Cochrane Library to identify relevant publications. A multimodal analysis was then conducted using Seed-based d Mapping software. Exploratory analyses included jackknife, subgroup and meta-regression analyses. We included 15 structural MRI studies comprising 486 drug-free patients and 485 healthy controls, and 16 functional MRI studies comprising 403 drug-free patients and 428 controls in our meta-analysis. Drug-free patients were examined to reduce pharmacological effects on the imaging data. Multimodal analysis showed considerable overlap between anatomic and functional changes, mainly in frontotemporal regions, bilateral medial posterior cingulate/paracingulate gyrus, bilateral insula, basal ganglia and left cerebellum. There were also brain regions showing only anatomic changes in the right superior frontal gyrus, left supramarginal gyrus, right lingual gyrus and functional alternations involving the right angular gyrus. The methodological aspects, patient characteristics and clinical variables of the included studies were heterogeneous, and we cannot exclude medication effects. The present study showed overlapping anatomic and functional brain abnormalities mainly in the default mode (DMN) and auditory networks (AN) in drug-free patients with schizophrenia. However, the pattern of changes differed in these networks. Decreased grey matter was associated with decreased activation within the DMN

  9. GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Guillermo Gonzalez-Burgos

    2011-01-01

    Full Text Available Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

  10. GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia.

    Science.gov (United States)

    Gonzalez-Burgos, Guillermo; Fish, Kenneth N; Lewis, David A

    2011-01-01

    Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

  11. Plasticity of cardiovascular function in snapping turtle embryos (Chelydra serpentina): chronic hypoxia alters autonomic regulation and gene expression.

    Science.gov (United States)

    Eme, John; Rhen, Turk; Tate, Kevin B; Gruchalla, Kathryn; Kohl, Zachary F; Slay, Christopher E; Crossley, Dane A

    2013-06-01

    Reptile embryos tolerate large decreases in the concentration of ambient oxygen. However, we do not fully understand the mechanisms that underlie embryonic cardiovascular short- or long-term responses to hypoxia in most species. We therefore measured cardiac growth and function in snapping turtle embryos incubated under normoxic (N21; 21% O₂) or chronic hypoxic conditions (H10; 10% O₂). We determined heart rate (fH) and mean arterial pressure (Pm) in acute normoxic (21% O₂) and acute hypoxic (10% O₂) conditions, as well as embryonic responses to cholinergic, adrenergic, and ganglionic pharmacological blockade. Compared with N21 embryos, chronic H10 embryos had smaller bodies and relatively larger hearts and were hypotensive, tachycardic, and following autonomic neural blockade showed reduced intrinsic fH at 90% of incubation. Unlike other reptile embryos, cholinergic and ganglionic receptor blockade both increased fH. β-Adrenergic receptor blockade with propranolol decreased fH, and α-adrenergic blockade with phentolamine decreased Pm. We also measured cardiac mRNA expression. Cholinergic tone was reduced in H10 embryos, but cholinergic receptor (Chrm2) mRNA levels were unchanged. However, expression of adrenergic receptor mRNA (Adrb1, Adra1a, Adra2c) and growth factor mRNA (Igf1, Igf2, Igf2r, Pdgfb) was lowered in H10 embryos. Hypoxia altered the balance between cholinergic receptors, α-adrenoreceptor and β-adrenoreceptor function, which was reflected in altered intrinsic fH and adrenergic receptor mRNA levels. This is the first study to link gene expression with morphological and cardioregulatory plasticity in a developing reptile embryo.

  12. Neonatal seizures alter NMDA glutamate receptor GluN2A and 3A subunit expression and function in hippocampal CA1 neurons

    Science.gov (United States)

    Zhou, Chengwen; Sun, Hongyu; Klein, Peter M.; Jensen, Frances E.

    2015-01-01

    Neonatal seizures are commonly caused by hypoxic and/or ischemic injury during birth and can lead to long-term epilepsy and cognitive deficits. In a rodent hypoxic seizure (HS) model, we have previously demonstrated a critical role for seizure-induced enhancement of the AMPA subtype of glutamate receptor (GluA) in epileptogenesis and cognitive consequences, in part due to GluA maturational upregulation of expression. Similarly, as the expression and function of the N-Methyl-D-aspartate (NMDA) subtype of glutamate receptor (GluN) is also developmentally controlled, we examined how early life seizures during the critical period of synaptogenesis could modify GluN development and function. In a postnatal day (P)10 rat model of neonatal seizures, we found that seizures could alter GluN2/3 subunit composition of GluNs and physiological function of synaptic GluNs. In hippocampal slices removed from rats within 48–96 h following seizures, the amplitudes of synaptic GluN-mediated evoked excitatory postsynaptic currents (eEPSCs) were elevated in CA1 pyramidal neurons. Moreover, GluN eEPSCs showed a decreased sensitivity to GluN2B selective antagonists and decreased Mg2+ sensitivity at negative holding potentials, indicating a higher proportion of GluN2A and GluN3A subunit function, respectively. These physiological findings were accompanied by a concurrent increase in GluN2A phosphorylation and GluN3A protein. These results suggest that altered GluN function and expression could potentially contribute to future epileptogenesis following neonatal seizures, and may represent potential therapeutic targets for the blockade of future epileptogenesis in the developing brain. PMID:26441533

  13. Habitat suitability and ecological niches of different plankton functional types in the global ocean

    Science.gov (United States)

    Vogt, Meike; Brun, Philipp; Payne, Mark R.; O'Brien, Colleen J.; Bednaršek, Nina; Buitenhuis, Erik T.; Doney, Scott C.; Leblanc, Karine; Le Quéré, Corinne; Luo, Yawei; Moriarty, Róisín; O'Brien, Todd D.; Schiebel, Ralf; Swan, Chantal

    2013-04-01

    Marine plankton play a central role in the biogeochemical cycling of important elements such as carbon, nitrogen, and sulphur. While our knowledge about marine ecosystem structure and functioning is still scarce and episodic, several recent observational studies confirm that marine ecosystems have been changing due to recent climate change, overfishing, and coastal eutrophication. In order to better understand marine ecosystem dynamics, the MAREDAT initiative has recently collected abundance and biomass data for 5 autotrophic (diatoms, Phaeocystis, coccolithophores, nitrogen fixers, picophytoplankton), and 6 heterotrophic plankton functional types (PFTs; bacteria, micro-, meso- and macrozooplankton, foraminifera and pteropods). Species distribution models (SDMs) are statistical tools that can be used to derive information about species habitats in space and time. They have been used extensively for a wide range of ecological applications in terrestrial ecosystems, but here we present the first global application in the marine realm, which was made possible by the MAREDAT data synthesis effort. We use a maximum entropy SDM to simulate global habitat suitability, habitat extent and ecological niches for different PFTs in the modern ocean. Present habitat suitability is derived from presence-only MAREDAT data and the observed annual and monthly mean levels of physiologically relevant variables such as SST, nutrient concentration or photosynthetic active radiation received in the mixed layer. This information can then be used to derive ecological niches for different species or taxa within each PFT, and to compare the ecological niches of different PFTs. While these results still need verification because data was not available for all ocean regions for all PFTs, they can give a first indication what present and future plankton habitats may look like, and what consequences we may have to expect for future marine ecosystem functioning and service provision in a warmer

  14. The policy relevance of global environmental change research

    International Nuclear Information System (INIS)

    Yarnal, Brent

    1996-01-01

    Many scientists are striving to identify and promote the policy implications of their global change research. Much basic research on global environmental change cannot advance policy directly, but new projects can determine the relevance of their research to decision makers and build policy-relevant products into the work. Similarly, many ongoing projects can alter or add to the present science design to make the research policy relevant. Thus, this paper shows scientists working on global change how to make their research policy relevant. It demonstrates how research on physical global change relates to human dimensions studies and integrated assessments. It also presents an example of how policy relevance can be fit retroactively into a global change project (in this case, SRBEX-the Susquehanna River Basin Experiment) and how that addition can enhance the project's status and science. The paper concludes that policy relevance is desirable from social and scientific perspectives

  15. Peripheral global neglect in high vs. low autistic tendency

    OpenAIRE

    Crewther, Daniel P.; Crewther, David P.

    2014-01-01

    In addition to its core social deficits, autism is characterized by altered visual perception, with a preference for local percept in those high in autistic tendency. Here, the balance of global vs. local percepts for the perceptually rivalrous diamond illusion was assessed between groups scoring high and low on the Autism Spectrum Quotient (AQ). The global percept of a diamond shape oscillating horizontally behind three occluders can as easily be interpreted as the local percept of four line...

  16. Peripheral global neglect in high versus low autistic tendency

    OpenAIRE

    Daniel Paul Crewther; David Philip Crewther

    2014-01-01

    In addition to its core social deficits, autism is characterised by altered visual perception, with a preference for local percept in those high in autistic tendency. Here, the balance of global versus local percepts for the perceptually rivalrous diamond illusion was assessed between groups scoring high and low on the Autism Spectrum Quotient (AQ). The global percept of a diamond shape oscillating horizontally behind three occluders can as easily be interpreted as the local percept of four l...

  17. Linking models of human behaviour and climate alters projected climate change

    Science.gov (United States)

    Beckage, Brian; Gross, Louis J.; Lacasse, Katherine; Carr, Eric; Metcalf, Sara S.; Winter, Jonathan M.; Howe, Peter D.; Fefferman, Nina; Franck, Travis; Zia, Asim; Kinzig, Ann; Hoffman, Forrest M.

    2018-01-01

    Although not considered in climate models, perceived risk stemming from extreme climate events may induce behavioural changes that alter greenhouse gas emissions. Here, we link the C-ROADS climate model to a social model of behavioural change to examine how interactions between perceived risk and emissions behaviour influence projected climate change. Our coupled climate and social model resulted in a global temperature change ranging from 3.4-6.2 °C by 2100 compared with 4.9 °C for the C-ROADS model alone, and led to behavioural uncertainty that was of a similar magnitude to physical uncertainty (2.8 °C versus 3.5 °C). Model components with the largest influence on temperature were the functional form of response to extreme events, interaction of perceived behavioural control with perceived social norms, and behaviours leading to sustained emissions reductions. Our results suggest that policies emphasizing the appropriate attribution of extreme events to climate change and infrastructural mitigation may reduce climate change the most.

  18. Is Traumatic and Non-Traumatic Neck Pain Associated with Brain Alterations? - A Systematic Review.

    Science.gov (United States)

    DePauw, Robby; Coppieters, Iris; Meeus, Mira; Caeyenberghs, Karen; Danneels, Lieven; Cagnie, Barbara

    2017-05-01

    Chronic neck pain affects 50% - 85% of people who have experienced an acute episode. This transition and the persistence of chronic complaints are believed to be mediated by brain alterations among different central mechanisms. This study aimed to systematically review and critically appraise the current existing evidence regarding structural and functional brain alterations in patients with whiplash associated disorders (WAD) and idiopathic neck pain (INP). Additionally, associations between brain alterations and clinical symptoms reported in neck pain patients were evaluated. Systematic review. The present systematic review was performed according to the PRISMA guidelines. PubMed, Web of Science, and Cochrane databases were searched. First, the obtained articles were screened based on title and abstract. Secondly, the screening was based on the full text. Risk of bias in included studies was investigated. Twelve studies met the inclusion criteria. Alterations in brain morphology and function, including perfusion, neurotransmission, and blood oxygenation level dependent-signal, were demonstrated in chronic neck pain patients. There is some to moderate evidence for both structural and functional brain alterations in patients with chronic neck pain. In contrast, no evidence for structural brain alterations in acute neck pain patients was found. Only 12 articles were included, which allows only cautious conclusions to be drawn. Brain alterations were observed in both patients with chronic WAD and chronic INP. Furthermore, more evidence exists for brain alterations in chronic WAD, and different underlying mechanisms might be present in both pathologies. In addition, pain and disability were correlated with the observed brain alterations. Accordingly, morphological and functional brain alterations should be further investigated in patients with chronic WAD and chronic INP with newer and more sensitive techniques, and associative clinical measurements seem indispensable

  19. Integral relations in complex space and the global analytic and monodromic structure of Green's functions in quantum field theory

    International Nuclear Information System (INIS)

    Bros, J.

    1980-01-01

    In this lecture, we present some of the ideas of a global consistent approach to the analytic and monodromic structure of Green's functions and scattering amplitudes of elementary particles on the basis of general quantum field theory. (orig.)

  20. Drought and Carbon Cycling of Grassland Ecosystems under Global Change: A Review

    Directory of Open Access Journals (Sweden)

    Tianjie Lei

    2016-10-01

    Full Text Available In recent years, the increased intensity and duration of droughts have dramatically altered the structure and function of grassland ecosystems, which have been forced to adapt to this change in climate. Combinations of global change drivers such as elevated atmospheric CO2 concentration, warming, nitrogen (N deposition, grazing, and land-use change have influenced the impact that droughts have on grassland C cycling. This influence, to some extent, can modify the relationship between droughts and grassland carbon (C cycling in the multi-factor world. Unfortunately, prior reviews have been primarily anecdotal from the 1930s to the 2010s. We investigated the current state of the study on the interactive impacts of multiple factors under drought scenarios in grassland C cycling and provided scientific advice for dealing with droughts and managing grassland C cycling in a multi-factor world. Currently, adequate information is not available on the interaction between droughts and global change drivers, which would advance our understanding of grassland C cycling responses. It was determined that future experiments and models should specifically test how droughts regulate grassland C cycling under global changes. Previous multi-factor experiments of current and future global change conditions have studied various drought scenarios poorly, including changes in precipitation frequency and amplitude, timing, and interactions with other global change drivers. Multi-factor experiments have contributed to quantifying these potential changes and have provided important information on how water affects ecosystem processes under global change. There is an urgent need to establish a systematic framework that can assess ecosystem dynamic responses to droughts under current and future global change and human activity, with a focus on the combined effects of droughts, global change drivers, and the corresponding hierarchical responses of an ecosystem.

  1. Green energy facilitated? The uncertain function of the global environment facility

    International Nuclear Information System (INIS)

    Young, Z.; Boehmer-Christiansen, S.

    1998-01-01

    The GEF remains the interim operating entity of the financial mechanism, the aid provider, for the Climate Change Convention (FCCC); It had 1.6 billion dollars to spend between 1994 and 1997 on the 'incremental costs' of implementing UN environmental conventions in eligible countries. The paper describes how this multilateral fund has functioned so far in the energy-environment arena, analyzing its governance and policies, decision-making criteria, project cycle and strategies for monitoring and evaluation. Through the patterns of GEF assistance to climate change related science, technologies and institutions, we explore the origins and wider purposes of the entity and in the process illuminate some assumptions and principles underlying the work of the GEF Secretariat and associated bureaucracies. What can realistically be expected should GEF become a more permanent fund for 'global environmental benefits' after current negotiations for its second replenishment? (author)

  2. Obesogenic diets alter metabolism in mice.

    Directory of Open Access Journals (Sweden)

    Megan R Showalter

    Full Text Available Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose, or very high fat diet (60%kcal fat/7% sucrose for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

  3. Obesogenic diets alter metabolism in mice.

    Science.gov (United States)

    Showalter, Megan R; Nonnecke, Eric B; Linderholm, A L; Cajka, Tomas; Sa, Michael R; Lönnerdal, Bo; Kenyon, Nicholas J; Fiehn, Oliver

    2018-01-01

    Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose), or very high fat diet (60%kcal fat/7% sucrose) for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

  4. Moving in the Anthropocene: Global reductions in terrestrial mammalian movements

    Science.gov (United States)

    Tucker, Marlee A.; Böhning-Gaese, Katrin; Fagan, William F.; Fryxell, John; Van Moorter, Bram; Alberts, Susan C; Ali, Abdullahi H.; Allen, Andrew M.; Attias, Nina; Avgar, Tal; Bartlam-Brooks, Hattie; Bayarbaatar, Buuveibaatar; Belant, Jerrold L.; Bertassoni, Alessandra; Beyer, Dean; Bidner, Laura; M. van Beest, Floris; Blake, Stephen; Blaum, Niels; Bracis, Chloe; Brown, Danielle; Nico de Bruyn, P. J.; Cagnacci, Francesca; Calabrese, J.M.; Camilo-Alves, Constança; Chamaillé-Jammes, Simon; Chiaradia, Andre; Davidson, Sarah C.; Dennis, Todd; DeStefano, Stephen; Diefenbach, Duane R.; Douglas-Hamilton, Iain; Fennessy, Julian; Fichtel, Claudia; Fiedler, Wolfgang; Fischer, Christina; Fischhoff, Ilya; Fleming, Christen H.; Ford, Adam T.; Fritz, Susanne A.; Gehr, Benedikt; Goheen, Jacob R.; Gurarie, Eliezer; Hebblewhite, Mark; Heurich, Marco; Mark Hewison, A.J.; Hof, Christian; Hurme, Edward; Isbell, Lynne A.; Janssen, René; Jeltsch, Florian; Kaczensky, Petra; Kane, Adam; Kappeler, Peter M.; Kauffman, Matthew J.; Kays, Roland; Kimuyu, Duncan; Koch, Flavia; Kranstauber, Bart; LaPoint, Scott; Leimgruber, Peter; Linnell, John D. C.; López-López, Pascual; Markham, A. Catherine; Mattisson, Jenny; Medici, Emilia Patricia; Mellone, Ugo; Merrill, E.; de Miranda Mourão, Guilherme; Morato, Ronaldo G.; Morellet, Nicolas; Morrison, Thomas A.; Díaz-Muñoz, Samuel L.; Mysterud, Atle; Nandintsetseg, Dejid; Nathan, Ran; Niamir, Aidin; Odden, John; O'Hara, Robert B.; Oliveira-Santos, Luiz G. R.; Olson, Kirk A.; Patterson, Bruce D.; Cunha de Paula, Rogerio; Pedrotti, Luca; Reineking, Björn; Rimmler, Martin; Rogers, T.L.; Rolandsen, Christer Moe; Rosenberry, Christopher S.; Rubenstein, Daniel I.; Safi, Kamran; Saïd, Sonia; Sapir, Nir; Sawyer, Hall; Schmidt, Niels Martin; Selva, Nuria; Sergiel, Agnieszka; Shiilegdamba, Enkhtuvshin; Silva, João Paulo; Singh, N.; Solberg, Erling J.; Spiegel, Orr; Strand, Olav; Sundaresan, S.R.; Ullmann, Wiebke; Voigt, Ulrich; Wall, J.; Wattles, David W.; Wikelski, Martin; Wilmers, Christopher C.; Wilson, Jon W.; Wittemyer, George; Zięba, Filip; Zwijacz-Kozica, Tomasz; Mueller, Thomas

    2018-01-01

    Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission.

  5. Early Stress History Alters Serum Insulin-Like Growth Factor-1 and Impairs Muscle Mitochondrial Function in Adult Male Rats.

    Science.gov (United States)

    Ghosh, S; Banerjee, K K; Vaidya, V A; Kolthur-Seetharam, U

    2016-09-01

    Early-life adversity is associated with an enhanced risk for adult psychopathology. Psychiatric disorders such as depression exhibit comorbidity for metabolic dysfunction, including obesity and diabetes. However, it is poorly understood whether, besides altering anxiety and depression-like behaviour, early stress also evokes dysregulation of metabolic pathways and enhances vulnerability for metabolic disorders. We used the rodent model of the early stress of maternal separation (ES) to examine the effects of early stress on serum metabolites, insulin-like growth factor (IGF)-1 signalling, and muscle mitochondrial content. Adult ES animals exhibited dyslipidaemia, decreased serum IGF1 levels, increased expression of liver IGF binding proteins, and a decline in the expression of specific metabolic genes in the liver and muscle, including Pck1, Lpl, Pdk4 and Hmox1. These changes occurred in the absence of alterations in body weight, food intake, glucose tolerance, insulin tolerance or insulin levels. ES animals also exhibited a decline in markers of muscle mitochondrial content, such as mitochondrial DNA levels and expression of TFAM (transcription factor A, mitochondrial). Furthermore, the expression of several genes involved in mitochondrial function, such as Ppargc1a, Nrf1, Tfam, Cat, Sesn3 and Ucp3, was reduced in skeletal muscle. Adult-onset chronic unpredictable stress resulted in overlapping and distinct consequences from ES, including increased circulating triglyceride levels, and a decline in the expression of specific metabolic genes in the liver and muscle, with no change in the expression of genes involved in muscle mitochondrial function. Taken together, our results indicate that a history of early adversity can evoke persistent changes in circulating IGF-1 and muscle mitochondrial function and content, which could serve to enhance predisposition for metabolic dysfunction in adulthood. © 2016 British Society for Neuroendocrinology.

  6. Dietary fat-dependent transcriptional architecture and copy number alterations associated with modifiers of mammary cancer metastasis

    DEFF Research Database (Denmark)

    Gordon, Ryan A; Merrill, Michele La; Hunter, Kent W

    2010-01-01

    Breast cancer is a complex disease resulting from a combination of genetic and environmental factors. Among environmental factors, body composition and intake of specific dietary components like total fat are associated with increased incidence of breast cancer and metastasis. We previously showed...... fat. To elucidate diet-dependent genetic modifiers of mammary cancer and metastasis risk, global gene expression profiles and copy number alterations from mammary cancers were measured and expression quantitative trait loci (eQTL) identified. Functional candidate genes that colocalized with previously...... detected metastasis modifiers were identified. Additional analyses, such as eQTL by dietary fat interaction analysis, causality and database evaluations, helped to further refine the candidate loci to produce an enriched list of genes potentially involved in the pathogenesis of metastatic mammary cancer...

  7. Uncertainty of Monetary Valued Ecosystem Services – Value Transfer Functions for Global Mapping

    Science.gov (United States)

    Schmidt, Stefan; Manceur, Ameur M.; Seppelt, Ralf

    2016-01-01

    Growing demand of resources increases pressure on ecosystem services (ES) and biodiversity. Monetary valuation of ES is frequently seen as a decision-support tool by providing explicit values for unconsidered, non-market goods and services. Here we present global value transfer functions by using a meta-analytic framework for the synthesis of 194 case studies capturing 839 monetary values of ES. For 12 ES the variance of monetary values could be explained with a subset of 93 study- and site-specific variables by utilizing boosted regression trees. This provides the first global quantification of uncertainties and transferability of monetary valuations. Models explain from 18% (water provision) to 44% (food provision) of variance and provide statistically reliable extrapolations for 70% (water provision) to 91% (food provision) of the terrestrial earth surface. Although the application of different valuation methods is a source of uncertainty, we found evidence that assuming homogeneity of ecosystems is a major error in value transfer function models. Food provision is positively correlated with better life domains and variables indicating positive conditions for human well-being. Water provision and recreation service show that weak ownerships affect valuation of other common goods negatively (e.g. non-privately owned forests). Furthermore, we found support for the shifting baseline hypothesis in valuing climate regulation. Ecological conditions and societal vulnerability determine valuation of extreme event prevention. Valuation of habitat services is negatively correlated with indicators characterizing less favorable areas. Our analysis represents a stepping stone to establish a standardized integration of and reporting on uncertainties for reliable and valid benefit transfer as an important component for decision support. PMID:26938447

  8. A new climate dataset for systematic assessments of climate change impacts as a function of global warming

    Directory of Open Access Journals (Sweden)

    J. Heinke

    2013-10-01

    Full Text Available In the ongoing political debate on climate change, global mean temperature change (ΔTglob has become the yardstick by which mitigation costs, impacts from unavoided climate change, and adaptation requirements are discussed. For a scientifically informed discourse along these lines, systematic assessments of climate change impacts as a function of ΔTglob are required. The current availability of climate change scenarios constrains this type of assessment to a narrow range of temperature change and/or a reduced ensemble of climate models. Here, a newly composed dataset of climate change scenarios is presented that addresses the specific requirements for global assessments of climate change impacts as a function of ΔTglob. A pattern-scaling approach is applied to extract generalised patterns of spatially explicit change in temperature, precipitation and cloudiness from 19 Atmosphere–Ocean General Circulation Models (AOGCMs. The patterns are combined with scenarios of global mean temperature increase obtained from the reduced-complexity climate model MAGICC6 to create climate scenarios covering warming levels from 1.5 to 5 degrees above pre-industrial levels around the year 2100. The patterns are shown to sufficiently maintain the original AOGCMs' climate change properties, even though they, necessarily, utilise a simplified relationships between ΔTglob and changes in local climate properties. The dataset (made available online upon final publication of this paper facilitates systematic analyses of climate change impacts as it covers a wider and finer-spaced range of climate change scenarios than the original AOGCM simulations.

  9. Globally-Optimized Local Pseudopotentials for (Orbital-Free) Density Functional Theory Simulations of Liquids and Solids.

    Science.gov (United States)

    Del Rio, Beatriz G; Dieterich, Johannes M; Carter, Emily A

    2017-08-08

    The accuracy of local pseudopotentials (LPSs) is one of two major determinants of the fidelity of orbital-free density functional theory (OFDFT) simulations. We present a global optimization strategy for LPSs that enables OFDFT to reproduce solid and liquid properties obtained from Kohn-Sham DFT. Our optimization strategy can fit arbitrary properties from both solid and liquid phases, so the resulting globally optimized local pseudopotentials (goLPSs) can be used in solid and/or liquid-phase simulations depending on the fitting process. We show three test cases proving that we can (1) improve solid properties compared to our previous bulk-derived local pseudopotential generation scheme; (2) refine predicted liquid and solid properties by adding force matching data; and (3) generate a from-scratch, accurate goLPS from the local channel of a non-local pseudopotential. The proposed scheme therefore serves as a full and improved LPS construction protocol.

  10. Alterations in the molecular species of rat liver lecithin by corn-oil feeding to essential fatty acid-deficient rats as a function of time

    NARCIS (Netherlands)

    Golde, L.M.G. van; Pieterson, W.A.; Deenen, L.L.M. van

    1968-01-01

    The present paper describes, as a function of time, the qualitative and quantitative alterations in the molecular species pattern of rat liver lecithin which are observed when corn oil is fed to essential fatty acid-deficient rats. One of the most important changes observed was a very rapid

  11. Altered spontaneous brain activity in patients with acute spinal cord injury revealed by resting-state functional MRI.

    Directory of Open Access Journals (Sweden)

    Ling Zhu

    Full Text Available Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI. However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo analysis based on resting-state functional magnetic resonance imaging.A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity.Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores.Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as potential biomarkers for

  12. SON68 glass alteration enhanced by magnetite

    Energy Technology Data Exchange (ETDEWEB)

    Godon, Nicole; Gin, Stephane; Rebiscoul, Diane; Frugier, Pierre [CEA, DEN-Marcoule, F30207, Bagnols-sur-Ceze (France)

    2013-07-01

    This paper reports experimental and modeling results of SON68 glass / magnetite interactions while in contact with synthetic groundwater from a clay environment. It is shown that magnetite enhances glass alteration, first by the sorption of Si released from the glass onto magnetite surfaces, then by a second process that could be the precipitation of an iron silicate mineral or the transformation of magnetite into a more reactive phase like hematite or goethite. This study globally suggests a detrimental effect of magnetite on the long-term durability of nuclear glass in geological disposal conditions. (authors)

  13. Searching for globally optimal functional forms for interatomic potentials using genetic programming with parallel tempering.

    Science.gov (United States)

    Slepoy, A; Peters, M D; Thompson, A P

    2007-11-30

    Molecular dynamics and other molecular simulation methods rely on a potential energy function, based only on the relative coordinates of the atomic nuclei. Such a function, called a force field, approximately represents the electronic structure interactions of a condensed matter system. Developing such approximate functions and fitting their parameters remains an arduous, time-consuming process, relying on expert physical intuition. To address this problem, a functional programming methodology was developed that may enable automated discovery of entirely new force-field functional forms, while simultaneously fitting parameter values. The method uses a combination of genetic programming, Metropolis Monte Carlo importance sampling and parallel tempering, to efficiently search a large space of candidate functional forms and parameters. The methodology was tested using a nontrivial problem with a well-defined globally optimal solution: a small set of atomic configurations was generated and the energy of each configuration was calculated using the Lennard-Jones pair potential. Starting with a population of random functions, our fully automated, massively parallel implementation of the method reproducibly discovered the original Lennard-Jones pair potential by searching for several hours on 100 processors, sampling only a minuscule portion of the total search space. This result indicates that, with further improvement, the method may be suitable for unsupervised development of more accurate force fields with completely new functional forms. Copyright (c) 2007 Wiley Periodicals, Inc.

  14. Streptozotocin alters glucose transport, connexin expression and endoplasmic reticulum functions in neurons and astrocytes.

    Science.gov (United States)

    Biswas, Joyshree; Gupta, Sonam; Verma, Dinesh Kumar; Singh, Sarika

    2017-07-25

    The study was undertaken to explore the cell-specific streptozotocin (STZ)-induced mechanistic alterations. STZ-induced rodent model is a well-established experimental model of Alzheimer's disease (AD) and in our previous studies we have established it as an in vitro screening model of AD by employing N2A neuronal cells. Therefore, STZ was selected in the present study to understand the STZ-induced cell-specific alterations by utilizing neuronal N2A and astrocytes C6 cells. Both neuronal and astrocyte cells were treated with STZ at 10, 50, 100 and 1000μM concentrations for 48h. STZ exposure caused significant decline in cellular viability and augmented cytotoxicity of cells involving astrocytes activation. STZ treatment also disrupted the energy metabolism by altered glucose uptake and its transport in both cells as reflected with decreased expression of glucose transporters (GLUT) 1/3. The consequent decrease in ATP level and decreased mitochondrial membrane potential was also observed in both the cells. STZ caused increased intracellular calcium which could cause the initiation of endoplasmic reticulum (ER) stress. Significant upregulation of ER stress-related markers were observed in both cells after STZ treatment. The cellular communication of astrocytes and neurons was altered as reflected by increased expression of connexin 43 along with DNA fragmentation. STZ-induced apoptotic death was evaluated by elevated expression of caspase-3 and PI/Hoechst staining of cells. In conclusion, study showed that STZ exert alike biochemical alterations, ER stress and cellular apoptosis in both neuronal and astrocyte cells. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Alterations to global but not local motion processing in long-term ecstasy (MDMA) users.

    Science.gov (United States)

    White, Claire; Brown, John; Edwards, Mark

    2014-07-01

    Growing evidence indicates that the main psychoactive ingredient in the illegal drug "ecstasy" (methylendioxymethamphetamine) causes reduced activity in the serotonin and gamma-aminobutyric acid (GABA) systems in humans. On the basis of substantial serotonin input to the occipital lobe, recent research investigated visual processing in long-term users and found a larger magnitude of the tilt aftereffect, interpreted to reflect broadened orientation tuning bandwidths. Further research found higher orientation discrimination thresholds and reduced long-range interactions in the primary visual area of ecstasy users. The aim of the present research was to investigate whether serotonin-mediated V1 visual processing deficits in ecstasy users extend to motion processing mechanisms. Forty-five participants (21 controls, 24 drug users) completed two psychophysical studies: A direction discrimination study directly measured local motion processing in V1, while a motion coherence task tested global motion processing in area V5/MT. "Primary" ecstasy users (n = 18), those without substantial polydrug use, had significantly lower global motion thresholds than controls [p = 0.027, Cohen's d = 0.78 (large)], indicating increased sensitivity to global motion stimuli, but no difference in local motion processing (p = 0.365). These results extend on previous research investigating the long-term effects of illicit drugs on visual processing. Two possible explanations are explored: defuse attentional processes may be facilitating spatial pooling of motion signals in users. Alternatively, it may be that a GABA-mediated disruption to V5/MT processing is reducing spatial suppression and therefore improving global motion perception in ecstasy users.

  16. The psychology of globalization.

    Science.gov (United States)

    Arnett, Jeffrey Jensen

    2002-10-01

    The influence of globalization on psychological functioning is examined. First, descriptions of how globalization is occurring in various world regions are presented. Then the psychological consequences of globalization are described, with a focus on identity issues. Specifically, it is argued that most people worldwide now develop a bicultural identity that combines their local identity with an identity linked to the global culture; that identity confusion may be increasing among young people in non-Western cultures as a result of globalization; that some people join self-selected cultures to maintain an identity that is separate from the global culture; and that a period of emerging adulthood increasingly extends identity explorations beyond adolescence, through the mid- to late twenties.

  17. Global adaptation in networks of selfish components: emergent associative memory at the system scale.

    Science.gov (United States)

    Watson, Richard A; Mills, Rob; Buckley, C L

    2011-01-01

    In some circumstances complex adaptive systems composed of numerous self-interested agents can self-organize into structures that enhance global adaptation, efficiency, or function. However, the general conditions for such an outcome are poorly understood and present a fundamental open question for domains as varied as ecology, sociology, economics, organismic biology, and technological infrastructure design. In contrast, sufficient conditions for artificial neural networks to form structures that perform collective computational processes such as associative memory/recall, classification, generalization, and optimization are well understood. Such global functions within a single agent or organism are not wholly surprising, since the mechanisms (e.g., Hebbian learning) that create these neural organizations may be selected for this purpose; but agents in a multi-agent system have no obvious reason to adhere to such a structuring protocol or produce such global behaviors when acting from individual self-interest. However, Hebbian learning is actually a very simple and fully distributed habituation or positive feedback principle. Here we show that when self-interested agents can modify how they are affected by other agents (e.g., when they can influence which other agents they interact with), then, in adapting these inter-agent relationships to maximize their own utility, they will necessarily alter them in a manner homologous with Hebbian learning. Multi-agent systems with adaptable relationships will thereby exhibit the same system-level behaviors as neural networks under Hebbian learning. For example, improved global efficiency in multi-agent systems can be explained by the inherent ability of associative memory to generalize by idealizing stored patterns and/or creating new combinations of subpatterns. Thus distributed multi-agent systems can spontaneously exhibit adaptive global behaviors in the same sense, and by the same mechanism, as with the organizational

  18. Sequential Optimization of Global Sequence Alignments Relative to Different Cost Functions

    KAUST Repository

    Odat, Enas M.

    2011-05-01

    The purpose of this dissertation is to present a methodology to model global sequence alignment problem as directed acyclic graph which helps to extract all possible optimal alignments. Moreover, a mechanism to sequentially optimize sequence alignment problem relative to different cost functions is suggested. Sequence alignment is mostly important in computational biology. It is used to find evolutionary relationships between biological sequences. There are many algo- rithms that have been developed to solve this problem. The most famous algorithms are Needleman-Wunsch and Smith-Waterman that are based on dynamic program- ming. In dynamic programming, problem is divided into a set of overlapping sub- problems and then the solution of each subproblem is found. Finally, the solutions to these subproblems are combined into a final solution. In this thesis it has been proved that for two sequences of length m and n over a fixed alphabet, the suggested optimization procedure requires O(mn) arithmetic operations per cost function on a single processor machine. The algorithm has been simulated using C#.Net programming language and a number of experiments have been done to verify the proved statements. The results of these experiments show that the number of optimal alignments is reduced after each step of optimization. Furthermore, it has been verified that as the sequence length increased linearly then the number of optimal alignments increased exponentially which also depends on the cost function that is used. Finally, the number of executed operations increases polynomially as the sequence length increase linearly.

  19. Left ventricular regional myocardial motion and twist function in repaired tetralogy of Fallot evaluated by magnetic resonance tissue phase mapping

    International Nuclear Information System (INIS)

    Chang, Meng-Chu; Peng, Hsu-Hsia; Wu, Ming-Ting; Weng, Ken-Pen; Su, Mao-Yuan; Menza, Marius; Huang, Hung-Chieh

    2018-01-01

    We aimed to characterise regional myocardial motion and twist function in the left ventricles (LV) in patients with repaired tetralogy of Fallot (rTOF) and preserved LV global function. We recruited 47 rTOF patients and 38 age-matched normal volunteers. Tissue phase mapping (TPM) was performed for evaluating the LV myocardial velocity in longitudinal, radial, and circumferential (Vz, Vr, and VOe) directions in basal, middle, and apical slices. The VOe peak-to-peak (PTP) during systolic phases, the rotation angle of each slice, and VOe inconsistency were computed for evaluating LV twist function and VOe dyssynchrony. As compared to the controls, the rTOF patients presented decreased RV ejection fraction (RVEF) (p = 0.002) and preserved global LV ejection fraction (LVEF). They also demonstrated decreased systolic and diastolic Vz in several LV segments and higher diastolic Vr in the septum (all p < 0.05). A lower VOe PTP, higher VOe inconsistency, and reduced peak net rotation angle (all p < 0.05) were observed. The aforementioned indices demonstrated an altered LV twist function in rTOF patients in an early disease stage. MR TPM could provide information about early abnormalities of LV regional motion and twist function in rTOF patients with preserved LV global function. (orig.)

  20. Left ventricular regional myocardial motion and twist function in repaired tetralogy of Fallot evaluated by magnetic resonance tissue phase mapping

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Meng-Chu; Peng, Hsu-Hsia [National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Wu, Ming-Ting [Kaohsiung Veterans General Hospital, Department of Radiology, Kaohsiung (China); National Yang-Ming University, Faculty of Medicine, Taipei (China); Weng, Ken-Pen [National Yang-Ming University, Faculty of Medicine, Taipei (China); Kaohsiung Veterans General Hospital, Department of Pediatrics, Kaohsiung (China); Shu-Zen Junior College of Medicine and Management, Department of Physical Therapy, Kaohsiung (China); Su, Mao-Yuan [National Taiwan University Hospital, Department of Medical Imaging, Taipei (China); Menza, Marius [Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Department of Radiology, Medical Physics, Freiburg (Germany); Huang, Hung-Chieh [Kaohsiung Veterans General Hospital, Department of Radiology, Kaohsiung (China)

    2018-01-15

    We aimed to characterise regional myocardial motion and twist function in the left ventricles (LV) in patients with repaired tetralogy of Fallot (rTOF) and preserved LV global function. We recruited 47 rTOF patients and 38 age-matched normal volunteers. Tissue phase mapping (TPM) was performed for evaluating the LV myocardial velocity in longitudinal, radial, and circumferential (Vz, Vr, and VOe) directions in basal, middle, and apical slices. The VOe peak-to-peak (PTP) during systolic phases, the rotation angle of each slice, and VOe inconsistency were computed for evaluating LV twist function and VOe dyssynchrony. As compared to the controls, the rTOF patients presented decreased RV ejection fraction (RVEF) (p = 0.002) and preserved global LV ejection fraction (LVEF). They also demonstrated decreased systolic and diastolic Vz in several LV segments and higher diastolic Vr in the septum (all p < 0.05). A lower VOe PTP, higher VOe inconsistency, and reduced peak net rotation angle (all p < 0.05) were observed. The aforementioned indices demonstrated an altered LV twist function in rTOF patients in an early disease stage. MR TPM could provide information about early abnormalities of LV regional motion and twist function in rTOF patients with preserved LV global function. (orig.)