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Sample records for revealed increased activity

  1. Sex differences in functional activation patterns revealed by increased emotion processing demands.

    Science.gov (United States)

    Hall, Geoffrey B C; Witelson, Sandra F; Szechtman, Henry; Nahmias, Claude

    2004-02-09

    Two [O(15)] PET studies assessed sex differences regional brain activation in the recognition of emotional stimuli. Study I revealed that the recognition of emotion in visual faces resulted in bilateral frontal activation in women, and unilateral right-sided activation in men. In study II, the complexity of the emotional face task was increased through tje addition of associated auditory emotional stimuli. Men again showed unilateral frontal activation, in this case to the left; whereas women did not show bilateral frontal activation, but showed greater limbic activity. These results suggest that when processing broader cross-modal emotional stimuli, men engage more in associative cognitive strategies while women draw more on primary emotional references.

  2. Near-infrared spectroscopy can reveal increases in brain activity related to animal-assisted therapy.

    Science.gov (United States)

    Morita, Yuka; Ebara, Fumio; Morita, Yoshimitsu; Horikawa, Etsuo

    2017-08-01

    [Purpose] Previous studies have indicated that animal-assisted therapy can promote recovery of psychological, social, and physiological function in mental disorders. This study was designed as a pilot evaluation of the use of near-infrared spectroscopy to objectively identify changes in brain activity that could mediate the effect of animal-assisted therapy. [Subjects and Methods] The participants were 20 healthy students (10 males and 10 females; age 19-21 years) of the Faculty of Agriculture, Saga University. Participants were shown a picture of a Tokara goat or shack (control) while prefrontal cortical oxygenated haemoglobin levels (representing neural activity) were measured by near-infrared spectroscopy. [Results] The prefrontal cortical near-infrared spectroscopy signal was significantly higher during viewing of the animal picture than during a rest condition or during viewing of the control picture. [Conclusion] Our results suggest that near-infrared spectroscopy can be used to objectively identify brain activity changes during human mentation regarding animals; furthermore, these preliminary results suggest the efficacy of animal-assisted therapy could be related to increased activation of the prefrontal cortex.

  3. Near-infrared spectroscopy can reveal increases in brain activity related to animal-assisted therapy

    OpenAIRE

    Morita, Yuka; Ebara, Fumio; Morita, Yoshimitsu; Horikawa, Etsuo

    2017-01-01

    [Purpose] Previous studies have indicated that animal-assisted therapy can promote recovery of psychological, social, and physiological function in mental disorders. This study was designed as a pilot evaluation of the use of near-infrared spectroscopy to objectively identify changes in brain activity that could mediate the effect of animal-assisted therapy. [Subjects and Methods] The participants were 20 healthy students (10 males and 10 females; age 19?21 years) of the Faculty of Agricultur...

  4. Depression-related increases and decreases in appetite reveal dissociable patterns of aberrant activity in reward and interoceptive neurocircuitry

    Science.gov (United States)

    Simmons, W. Kyle; Burrows, Kaiping; Avery, Jason A.; Kerr, Kara L.; Bodurka, Jerzy; Savage, Cary R.; Drevets, Wayne C.

    2016-01-01

    Objective Appetite and weight changes are common but variable diagnostic markers in major depressive disorder: some depressed individuals manifest increased appetite, while others lose their appetite. Many of the brain regions implicated in appetitive responses to food have also been implicated in depression. It is thus remarkable that there exists no published research comparing the neural responses to food stimuli of depressed patients with increased versus decreased appetites. Method Using functional magnetic resonance imaging we compared brain activity in unmedicated depressed patients with increased or decreased appetite, and healthy control subjects, while viewing photographs of food and non-food objects. We also measured how resting-state functional connectivity related to subjects’ food pleasantness ratings. Results Within putative reward regions, depressed participants with increased appetites exhibited greater hemodynamic activity to food stimuli than both those reporting appetite decreases and healthy control subjects. In contrast, depressed subjects experiencing appetite loss exhibited hypoactivation within a region of the mid-insula implicated in interoception, with no difference observed in this region between healthy subjects and those with depression-related appetite increases. Mid-insula activity was negatively correlated with food pleasantness ratings of depressed participants with increased appetites, and its functional connectivity to reward circuitry was positively correlated with food pleasantness ratings. Conclusions Depression-related increases in appetite are associated with hyperactivation of putative mesocorticolimbic reward circuitry, while depression-related appetite loss is associated with hypoactivation of insular regions that support monitoring the body’s physiological state. Importantly, the interactions among these regions also contribute to individual differences in the depression-related appetite changes. PMID:26806872

  5. Increased fusiform area activation in schizophrenia during processing of spatial frequency-degraded faces, as revealed by fMRI.

    Science.gov (United States)

    Silverstein, S M; All, S D; Kasi, R; Berten, S; Essex, B; Lathrop, K L; Little, D M

    2010-07-01

    People with schizophrenia demonstrate perceptual organization impairments, and these are thought to contribute to their face processing difficulties. We examined the neural substrates of emotionally neutral face processing in schizophrenia by investigating neural activity under three stimulus conditions: faces characterized by the full spectrum of spatial frequencies, faces with low spatial frequency information removed [high spatial frequency (HSF) condition], and faces with high spatial frequency information removed [low spatial frequency (LSF) condition]. Face perception in the HSF condition is more reliant on local feature processing whereas perception in the LSF condition requires greater reliance on global form processing. Past studies of perceptual organization in schizophrenia indicate that patients perform relatively more poorly with degraded stimuli but also that, when global information is absent, patients may perform better than controls because of their relatively increased ability to initially process individual features. Therefore, we hypothesized that people with schizophrenia (n=14) would demonstrate greater face processing difficulties than controls (n=13) in the LSF condition, whereas they would demonstrate a smaller difference or superior performance in the HSF condition. In a gender-discrimination task, behavioral data indicated high levels of accuracy for both groups, with a trend toward an interaction involving higher patient performance in the HSF condition and poorer patient performance in the LSF condition. Patients demonstrated greater activity in the fusiform gyrus compared to controls in both degraded conditions. These data suggest that impairments in basic integration abilities may be compensated for by relatively increased activity in this region.

  6. Transcriptomic profiling of diverse Aedes aegypti strains reveals increased basal-level immune activation in dengue virus-refractory populations and identifies novel virus-vector molecular interactions.

    Directory of Open Access Journals (Sweden)

    Shuzhen Sim

    Full Text Available Genetic variation among Aedes aegypti populations can greatly influence their vector competence for human pathogens such as the dengue virus (DENV. While intra-species transcriptome differences remain relatively unstudied when compared to coding sequence polymorphisms, they also affect numerous aspects of mosquito biology. Comparative molecular profiling of mosquito strain transcriptomes can therefore provide valuable insight into the regulation of vector competence. We established a panel of A. aegypti strains with varying levels of susceptibility to DENV, comprising both laboratory-maintained strains and field-derived colonies collected from geographically distinct dengue-endemic regions spanning South America, the Caribbean, and Southeast Asia. A comparative genome-wide gene expression microarray-based analysis revealed higher basal levels of numerous immunity-related gene transcripts in DENV-refractory mosquito strains than in susceptible strains, and RNA interference assays further showed different degrees of immune pathway contribution to refractoriness in different strains. By correlating transcript abundance patterns with DENV susceptibility across our panel, we also identified new candidate modulators of DENV infection in the mosquito, and we provide functional evidence for two potential DENV host factors and one potential restriction factor. Our comparative transcriptome dataset thus not only provides valuable information about immune gene regulation and usage in natural refractoriness of mosquito populations to dengue virus but also allows us to identify new molecular interactions between the virus and its mosquito vector.

  7. Neurons derived from sporadic Alzheimer's disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation

    DEFF Research Database (Denmark)

    Ochalek, Anna; Mihalik, Balázs; Avci, Hasan X.

    2017-01-01

    , our aim was to establish an in vitro cell model based on patient-specific human neurons to study the pathomechanism of sporadic AD. Methods: We compared neurons derived from induced pluripotent stem cell (iPSC) lines of patients with early-onset familial Alzheimer's disease (fAD), all caused...... blotting methods. Results: Neurons from patients with fAD and patients with sAD showed increased phosphorylation of TAU protein at all investigated phosphorylation sites. Relative to the control neurons, neurons derived from patients with fAD and patients with sAD exhibited higher levels of extracellular......, a physiological kinase of TAU, in neurons derived from AD iPSCs, as well as significant upregulation of amyloid precursor protein (APP) synthesis and APP carboxy-terminal fragment cleavage. Moreover, elevated sensitivity to oxidative stress, as induced by amyloid oligomers or peroxide, was detected in both f...

  8. Assessing and Increasing Physical Activity

    Science.gov (United States)

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  9. Increasing Youth Physical Activity with Activity Calendars

    Science.gov (United States)

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  10. Monitoring health spending increases: incremental budget analyses reveal challenging tradeoffs.

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    Hartman, Micah; Smith, Cynthia; Heffler, Stephen; Freeland, Mark

    2006-01-01

    With each passing decade, health care has consumed a larger share of gross domestic product (GDP) and Federal budgets. By the 2000-2004 period, society was willing to devote over 20 percent of the cumulative increase in GDP and the cumulative increase in Federal outlays towards health care. The financing challenges are expected to become more acute for private payers as well as Federal, State, and local budgets. With the implementation of Part D in 2006, the U.S. Office of Management and Budget projects that Federal budget pressures will heighten, bringing increased attention to Medicare's long-term fiscal outlook.

  11. Increased taxon sampling reveals thousands of hidden orthologs in flatworms

    Science.gov (United States)

    2017-01-01

    Gains and losses shape the gene complement of animal lineages and are a fundamental aspect of genomic evolution. Acquiring a comprehensive view of the evolution of gene repertoires is limited by the intrinsic limitations of common sequence similarity searches and available databases. Thus, a subset of the gene complement of an organism consists of hidden orthologs, i.e., those with no apparent homology to sequenced animal lineages—mistakenly considered new genes—but actually representing rapidly evolving orthologs or undetected paralogs. Here, we describe Leapfrog, a simple automated BLAST pipeline that leverages increased taxon sampling to overcome long evolutionary distances and identify putative hidden orthologs in large transcriptomic databases by transitive homology. As a case study, we used 35 transcriptomes of 29 flatworm lineages to recover 3427 putative hidden orthologs, some unidentified by OrthoFinder and HaMStR, two common orthogroup inference algorithms. Unexpectedly, we do not observe a correlation between the number of putative hidden orthologs in a lineage and its “average” evolutionary rate. Hidden orthologs do not show unusual sequence composition biases that might account for systematic errors in sequence similarity searches. Instead, gene duplication with divergence of one paralog and weak positive selection appear to underlie hidden orthology in Platyhelminthes. By using Leapfrog, we identify key centrosome-related genes and homeodomain classes previously reported as absent in free-living flatworms, e.g., planarians. Altogether, our findings demonstrate that hidden orthologs comprise a significant proportion of the gene repertoire in flatworms, qualifying the impact of gene losses and gains in gene complement evolution. PMID:28400424

  12. SAFARI: Searching Asteroids For Activity Revealing Indicators

    Science.gov (United States)

    Curtis, Anthony; Chandler, Colin Orion; Mommert, Michael; Sheppard, Scott; Trujillo, Chadwick A.

    2018-06-01

    We present results on one of the deepest and widest systematic searches for active asteroids, objects in the main-belt which behave dynamically like asteroids but display comet-like comae. This activity comes from a variety of sources, such as the sublimation of ices or rotational breakup, the former of which offers an opportunity to study a family of protoplanetary ices different than those seen in comets and Kuiper Belt objects. Indications of activity may be detected through visual or spectroscopic evidence of gas or dust emissions. However, these objects are still poorly understood, with only about 25 identified to date. We looked for activity indicators with a pipeline that examined ~35,000 deep images taken with the Dark Energy Camera (DECam) mounted on the 4-meter Blanco telescope at the Cerro Tololo Inter-American Observatory in Chile. Our pipeline was configured to perform astrometry on DECam images and produce thumbnail images of known asteroids in the field to be examined by eye for signs of activity. We detected three previously identified active asteroids, one of which has shown repeated signs of activity in these data. Our proof of concept demonstrates 1) our novel informatics approach can locate active asteroids 2) DECam data are well suited to search for active asteroids. We will discuss the design structure of our pipeline, adjustments that had to be made for the specific dataset to improve performance, and the the significance of detecting activity in the main-belt. The authors acknowledge funding for this project through NSF grant number AST-1461200.

  13. Combined Increases in Muscle-Strengthening Activity Frequency and Protein Intake Reveal Graded Relationship with Fat-Free Mass Percentage in U.S. Adults, NHANES (1999-2004).

    Science.gov (United States)

    Kurka, J M; Vezina, J; Brown, D D; Schumacher, J; Cullen, R W; Laurson, K R

    2015-01-01

    Age-related loss of muscle mass and related ailments are of concern due to associations with disabilities and morbidity as well as constituting a substantial healthcare burden. Muscle-strengthening activities and adequate protein ingestion are recommended for all-age adults in an effort to stave off age-related muscle atrophy. Muscle building abilities decline with age but most research focuses on muscle wasting in the elderly. To examine the independent and combined associations of protein intake (g∙kg-1∙day-1) and muscle-strengthening frequency (times∙week-1, MSF) on fat-free mass percentage (FFM%). This cross-sectional analysis of a population-based sample with data from the non-institutionalized persons in the United States participating in the National Health and Nutrition Examination Survey (cycles 1999-2000, 2001-2002, 2003-2004) consisted of male (n=2,499) and female (n=2,373) participants 20-49 years of age for analyses. MSF was determined by self-report and protein intake was calculated from a 24-hour recall. Differences in FFM% from bioelectrical impedance analysis was estimated using multiple linear regression models controlling for education, race-ethnicity, standing height, and total Caloric intake. One unit increase in MSF or protein intake (β-coefficient, ±E) was associated with significantly more FFM% in males (0.6±0.1%; 3.5±0.4%) and females (0.4±0.1%; 5.9±0.4%). Independent of protein intake, males and females with MSF=0 had mean ±SE FFM% of 74.4±0.4 and 60.7±0.3, respectively, while mean ±SE FFM% of males and females who met the recommendation of ≥2 times per week were 77.9±0.5 and 63.0±0.4. Independent of MSF, males and females with protein intakes below the recommended dietary allowance (RDA) of 0.8 g∙kg-1∙day-1 had mean ±SE FFM% of 74.0±0.6 and 58.2±0.6, respectively, while mean ±SE FFM% of those whose intakes exceeded the recommendation were 75.6±0.4 and 62.0±0.4. The subgroup with the highest mean ±SE FFM% (80

  14. Barriers to increased market-oriented activity

    DEFF Research Database (Denmark)

    Bisp, Søren

    1999-01-01

    and related activities still seem to attract relatively few resources is not answered by supplying another checklist or package of facilitators. Based on published conceptual writings and empirical studies this article makes an account of what the intra-organizational barriers may be to increased market......Most research on market orientation has dealt with assessing how market orientation behaviour is related to business performance. This work has established an intense market-oriented activity as significantly and positively related to business performance under most circumstances. In a maturing......-oriented activity. A framework of six generic domains is suggested: Organizational structure, human resource management, market-oriented activity competence, psychological climate, managers' personality characteristics, and individually held beliefs. A model is suggested inter-relating the domains....

  15. Clusters - Tourism Activity Increase Competitiveness Support

    Directory of Open Access Journals (Sweden)

    Carmen IORDACHE

    2010-05-01

    Full Text Available Tourism represents one of those areas with the greatest potential of global expansion. Tourism development strategy in terms of maximizing its positive effects on regional economic increase and implicitly on the national one starts from the premise that in global economy value is created in regions which are defined as particular geographical entities, separated by geographical reasons and not as political-administrative structures, and economic increase is centrally cumulated and valued according to the economic policy and the national legal system.Regional economic system approach based on “cluster” concept is explained by the fact that the regional activities portfolio is based on an inter and intra-industry networking grouped by cluster, in which is created the value that increases as the activity results are leading to the final consumers.This type of communication aims to highlight the tourism role as a factor in regional development, the clustering process significance in obtaining some competitiveness advantages, clusters development in tourism beginnings, and also the identification methodology used to select one touristic area to create the cluster.

  16. Workplace pedometer interventions for increasing physical activity.

    Science.gov (United States)

    Freak-Poli, Rosanne L A; Cumpston, Miranda; Peeters, Anna; Clemes, Stacy A

    2013-04-30

    The World Health Organization and the World Economic Forum have recommended further research to strengthen current knowledge of workplace health programmes, particularly on effectiveness and using simple instruments. A pedometer is one such simple instrument that can be incorporated in workplace interventions. To assess the effectiveness of pedometer interventions in the workplace for increasing physical activity and improving subsequent health outcomes. Electronic searches of the Cochrane Central Register of Controlled Trials (671 potential papers), MEDLINE (1001), Embase (965), CINAHL (1262), OSH UPDATE databases (75) and Web of Science (1154) from the earliest record to between 30th January and 6th February 2012 yielded 3248 unique records. Reference lists of articles yielded an additional 34 papers. Contact with individuals and organisations did not produce any further records. We included individual and cluster-randomised controlled trials of workplace health promotion interventions with a pedometer component in employed adults. The primary outcome was physical activity and was part of the eligibility criteria. We considered subsequent health outcomes, including adverse effects, as secondary outcomes. Two review authors undertook the screening of titles and abstracts and the full-text papers independently. Two review authors (RFP and MC) independently completed data extraction and risk of bias assessment. We contacted authors to obtain additional data and clarification. We found four relevant studies providing data for 1809 employees, 60% of whom were allocated to the intervention group. All studies assessed outcomes immediately after the intervention had finished and the intervention duration varied between three to six months. All studies had usual treatment control conditions; however one study's usual treatment was an alternative physical activity programme while the other three had minimally active controls. In general, there was high risk of bias mainly

  17. Community wide interventions for increasing physical activity.

    Science.gov (United States)

    Baker, Philip R A; Francis, Daniel P; Soares, Jesus; Weightman, Alison L; Foster, Charles

    2015-01-05

    Multi-strategic community wide interventions for physical activity are increasingly popular but their ability to achieve population level improvements is unknown. To evaluate the effects of community wide, multi-strategic interventions upon population levels of physical activity. We searched the Cochrane Public Health Group Segment of the Cochrane Register of Studies,The Cochrane Library, MEDLINE, MEDLINE in Process, EMBASE, CINAHL, LILACS, PsycINFO, ASSIA, the British Nursing Index, Chinese CNKI databases, EPPI Centre (DoPHER, TRoPHI), ERIC, HMIC, Sociological Abstracts, SPORT Discus, Transport Database and Web of Science (Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index). We also scanned websites of the EU Platform on Diet, Physical Activity and Health; Health-Evidence.org; the International Union for Health Promotion and Education; the NIHR Coordinating Centre for Health Technology (NCCHTA); the US Centre for Disease Control and Prevention (CDC) and NICE and SIGN guidelines. Reference lists of all relevant systematic reviews, guidelines and primary studies were searched and we contacted experts in the field. The searches were updated to 16 January 2014, unrestricted by language or publication status. Cluster randomised controlled trials, randomised controlled trials, quasi-experimental designs which used a control population for comparison, interrupted time-series studies, and prospective controlled cohort studies were included. Only studies with a minimum six-month follow up from the start of the intervention to measurement of outcomes were included. Community wide interventions had to comprise at least two broad strategies aimed at physical activity for the whole population. Studies which randomised individuals from the same community were excluded. At least two review authors independently extracted the data and assessed the risk of bias. Each study was assessed for the setting, the number of included components

  18. Community wide interventions for increasing physical activity.

    Science.gov (United States)

    Baker, Philip Ra; Francis, Daniel P; Soares, Jesus; Weightman, Alison L; Foster, Charles

    2011-04-13

    Multi-strategic community wide interventions for physical activity are increasingly popular but their ability to achieve population level improvements is unknown. To evaluate the effects of community wide, multi-strategic interventions upon population levels of physical activity. We searched the Cochrane Public Health Group Specialised Register, The Cochrane Library, MEDLINE, MEDLINE in Process, EMBASE, CINAHL, LILACS, PsycINFO, ASSIA, The British Nursing Index, Chinese CNKI databases, EPPI Centre (DoPHER, TRoPHI), ERIC, HMIC, Sociological Abstracts, SPORTDiscus, Transport Database and Web of Science (Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index). We also scanned websites of the EU Platform on Diet, Physical Activity and Health; Health-Evidence.ca; the International Union for Health Promotion and Education; the NIHR Coordinating Centre for Health Technology (NCCHTA) and NICE and SIGN guidelines. Reference lists of all relevant systematic reviews, guidelines and primary studies were followed up. We contacted experts in the field from the National Obesity Observatory Oxford, Oxford University; Queensland Health, Queensland University of Technology, the University of Central Queensland; the University of Tennessee and Washington University; and handsearched six relevant journals. The searches were last updated to the end of November 2009 and were not restricted by language or publication status. Cluster randomised controlled trials, randomised controlled trials (RCT), quasi-experimental designs which used a control population for comparison, interrupted time-series (ITS) studies, and prospective controlled cohort studies (PCCS) were included. Only studies with a minimum six-month follow up from the start of the intervention to measurement of outcomes were included. Community wide interventions had to comprise at least two broad strategies aimed at physical activity for the whole population. Studies which randomised

  19. Active Learning Increases Children's Physical Activity across Demographic Subgroups.

    Science.gov (United States)

    Bartholomew, John B; Jowers, Esbelle M; Roberts, Gregory; Fall, Anna-Mária; Errisuriz, Vanessa L; Vaughn, Sharon

    2018-01-01

    Given the need to find more opportunities for physical activity within the elementary school day, this study was designed to asses the impact of I-CAN!, active lessons on: 1) student physical activity (PA) outcomes via accelerometry; and 2) socioeconomic status (SES), race, sex, body mass index (BMI), or fitness as moderators of this impact. Participants were 2,493 fourth grade students (45.9% male, 45.8% white, 21.7% low SES) from 28 central Texas elementary schools randomly assigned to intervention (n=19) or control (n=9). Multilevel regression models evaluated the effect of I-CAN! on PA and effect sizes were calculated. The moderating effects of SES, race, sex, BMI, and fitness were examined in separate models. Students in treatment schools took significantly more steps than those in control schools (β = 125.267, SE = 41.327, p = .002, d = .44). I-CAN! had a significant effect on MVPA with treatment schools realizing 80% (β = 0.796, SE =0.251, p = .001; d = .38) more MVPA than the control schools. There were no significant school-level differences on sedentary behavior (β = -0.177, SE = 0.824, p = .83). SES, race, sex, BMI, and fitness level did not moderate the impact of active learning on step count and MVPA. Active learning increases PA within elementary students, and does so consistently across demographic sub-groups. This is important as these sub-groups represent harder to reach populations for PA interventions. While these lessons may not be enough to help children reach daily recommendations of PA, they can supplement other opportunities for PA. This speaks to the potential of schools to adopt policy change to require active learning.

  20. Exercising self-control increases relative left frontal cortical activation.

    Science.gov (United States)

    Schmeichel, Brandon J; Crowell, Adrienne; Harmon-Jones, Eddie

    2016-02-01

    Self-control refers to the capacity to override or alter a predominant response tendency. The current experiment tested the hypothesis that exercising self-control temporarily increases approach motivation, as revealed by patterns of electrical activity in the prefrontal cortex. Participants completed a writing task that did vs did not require them to exercise self-control. Then they viewed pictures known to evoke positive, negative or neutral affect. We assessed electroencephalographic (EEG) activity while participants viewed the pictures, and participants reported their trait levels of behavioral inhibition system (BIS) and behavioral activation system (BAS) sensitivity at the end of the study. We found that exercising (vs not exercising) self-control increased relative left frontal cortical activity during picture viewing, particularly among individuals with relatively higher BAS than BIS, and particularly during positive picture viewing. A similar but weaker pattern emerged during negative picture viewing. The results suggest that exercising self-control temporarily increases approach motivation, which may help to explain the aftereffects of self-control (i.e. ego depletion). © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  1. Invasive Glioblastoma Cells Acquire Stemness and Increased Akt Activation

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    Jennifer R. Molina

    2010-06-01

    Full Text Available Glioblastoma multiforme (GBM is the most frequent and most aggressive brain tumor in adults. The dismal prognosis is due to postsurgery recurrences arising from escaped invasive tumor cells. The signaling pathways activated in invasive cells are under investigation, and models are currently designed in search for therapeutic targets. We developed here an in vivo model of human invasive GBM in mouse brain from a GBM cell line with moderate tumorigenicity that allowed simultaneous primary tumor growth and dispersal of tumor cells in the brain parenchyma. This strategy allowed for the first time the isolation and characterization of matched sets of tumor mass (Core and invasive (Inv cells. Both cell populations, but more markedly Inv cells, acquired stem cell markers, neurosphere renewal ability, and resistance to rapamycin-induced apoptosis relative to parental cells. The comparative phenotypic analysis between Inv and Core cells showed significantly increased tumorigenicity in vivo and increased invasion with decreased proliferation in vitro for Inv cells. Examination of a large array of signaling pathways revealed extracellular signal-regulated kinase (Erk down-modulation and Akt activation in Inv cells and an opposite profile in Core cells. Akt activation correlated with the increased tumorigenicity, stemness, and invasiveness, whereas Erk activation correlated with the proliferation of the cells. These results underscore complementary roles of the Erk and Akt pathways for GBM proliferation and dispersal and raise important implications for a concurrent inhibitory therapy.

  2. Fire activity increasing as climate changes

    Science.gov (United States)

    Balcerak, Ernie; Showstack, Randy

    2013-01-01

    Analysis of images from NASA's Moderate Resolution Imaging Spectroradiometer (MODIS) satellites shows that more than 2.5 million hectares were burned in 2012 from January through August in the United States. The amount is less than a record 3.2 million hectares in 2011 but greater than the area burned in 12 of 15 years since satellite monitoring began, scientists reported at the AGU Fall Meeting. With satellites "we can detect fires as they're actively burning," said Louis Giglio of the University of Maryland, College Park, at a press conference on 4 December. "We can also map the cumulative area burned on the landscape after the fire's over." He noted that "2012 has been a particularly big fire year" in the United States.

  3. Growth and carbon isotopes of Mediterranean trees reveal contrasting responses to increased carbon dioxide and drought.

    Science.gov (United States)

    Granda, Elena; Rossatto, Davi Rodrigo; Camarero, J Julio; Voltas, Jordi; Valladares, Fernando

    2014-01-01

    Forest dynamics will depend upon the physiological performance of individual tree species under more stressful conditions caused by climate change. In order to compare the idiosyncratic responses of Mediterranean tree species (Quercus faginea, Pinus nigra, Juniperus thurifera) coexisting in forests of central Spain, we evaluated the temporal changes in secondary growth (basal area increment; BAI) and intrinsic water-use efficiency (iWUE) during the last four decades, determined how coexisting species are responding to increases in atmospheric CO2 concentrations (C(a)) and drought stress, and assessed the relationship among iWUE and growth during climatically contrasting years. All species increased their iWUE (ca. +15 to +21%) between the 1970s and the 2000s. This increase was positively related to C(a) for J. thurifera and to higher C(a) and drought for Q. faginea and P. nigra. During climatically favourable years the study species either increased or maintained their growth at rising iWUE, suggesting a higher CO2 uptake. However, during unfavourable climatic years Q. faginea and especially P. nigra showed sharp declines in growth at enhanced iWUE, likely caused by a reduced stomatal conductance to save water under stressful dry conditions. In contrast, J. thurifera showed enhanced growth also during unfavourable years at increased iWUE, denoting a beneficial effect of C(a) even under climatically harsh conditions. Our results reveal significant inter-specific differences in growth driven by alternative physiological responses to increasing drought stress. Thus, forest composition in the Mediterranean region might be altered due to contrasting capacities of coexisting tree species to withstand increasingly stressful conditions.

  4. Functional metabolomics reveals novel active products in the DHA metabolome

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    Masakazu eShinohara

    2012-04-01

    Full Text Available Endogenous mechanisms for successful resolution of an acute inflammatory response and the local return to homeostasis are of interest because excessive inflammation underlies many human diseases. In this review, we provide an update and overview of functional metabolomics that identified a new bioactive metabolome of docosahexaenoic acid (DHA. Systematic studies revealed that DHA was converted to DHEA-derived novel bioactive products as well as aspirin-triggered (AT forms of protectins. The new oxygenated DHEA derived products blocked PMN chemotaxis, reduced P-selectin expression and platelet-leukocyte adhesion, and showed organ protection in ischemia/reperfusion injury. These products activated cannabinoid receptor (CB2 receptor and not CB1 receptors. The AT-PD1 reduced neutrophil (PMN recruitment in murine peritonitis. With human cells, AT-PD1 decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. The recent findings reviewed here indicate that DHEA oxidative metabolism and aspirin-triggered conversion of DHA produce potent novel molecules with anti-inflammatory and organ-protective properties, opening the DHA metabolome functional roles.

  5. Increased serum cortisol binding in chronic active hepatitis

    International Nuclear Information System (INIS)

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG

  6. Interacting with wildlife tourism increases activity of white sharks.

    Science.gov (United States)

    Huveneers, Charlie; Watanabe, Yuuki Y; Payne, Nicholas L; Semmens, Jayson M

    2018-01-01

    Anthropogenic activities are dramatically changing marine ecosystems. Wildlife tourism is one of the fastest growing sectors of the tourism industry and has the potential to modify the natural environment and behaviour of the species it targets. Here, we used a novel method to assess the effects of wildlife tourism on the activity of white sharks ( Carcharodon carcharias ). High frequency three-axis acceleration loggers were deployed on ten white sharks for a total of ~9 days. A combination of multivariate and univariate analysis revealed that the increased number of strong accelerations and vertical movements when sharks are interacting with cage-diving operators result in an overall dynamic body acceleration (ODBA) ~61% higher compared with other times when sharks are present in the area where cage-diving occurs. Since ODBA is considered a proxy of metabolic rate, interacting with cage-divers is probably more costly than are normal behaviours of white sharks at the Neptune Islands. However, the overall impact of cage-diving might be small if interactions with individual sharks are infrequent. This study suggests wildlife tourism changes the instantaneous activity levels of white sharks, and calls for an understanding of the frequency of shark-tourism interactions to appreciate the net impact of ecotourism on this species' fitness.

  7. Neural activity reveals perceptual grouping in working memory.

    Science.gov (United States)

    Rabbitt, Laura R; Roberts, Daniel M; McDonald, Craig G; Peterson, Matthew S

    2017-03-01

    There is extensive evidence that the contralateral delay activity (CDA), a scalp recorded event-related brain potential, provides a reliable index of the number of objects held in visual working memory. Here we present evidence that the CDA not only indexes visual object working memory, but also the number of locations held in spatial working memory. In addition, we demonstrate that the CDA can be predictably modulated by the type of encoding strategy employed. When individual locations were held in working memory, the pattern of CDA modulation mimicked previous findings for visual object working memory. Specifically, CDA amplitude increased monotonically until working memory capacity was reached. However, when participants were instructed to group individual locations to form a constellation, the CDA was prolonged and reached an asymptote at two locations. This result provides neural evidence for the formation of a unitary representation of multiple spatial locations. Published by Elsevier B.V.

  8. Increased microglial catalase activity in multiple sclerosis grey matter.

    Science.gov (United States)

    Gray, Elizabeth; Kemp, Kevin; Hares, Kelly; Redondo, Julianna; Rice, Claire; Scolding, Neil; Wilkins, Alastair

    2014-04-22

    Chronic demyelination, on-going inflammation, axonal loss and grey matter neuronal injury are likely pathological processes that contribute to disease progression in multiple sclerosis (MS). Although the precise contribution of each process and their aetiological substrates is not fully known, recent evidence has implicated oxidative damage as a major cause of tissue injury in MS. The degree of tissue injury caused by oxidative molecules, such as reactive oxygen species (ROS), is balanced by endogenous anti-oxidant enzymes which detoxify ROS. Understanding endogenous mechanisms which protect the brain against oxidative injury in MS is important, since enhancing anti-oxidant responses is a major therapeutic strategy for preventing irreversible tissue injury in the disease. Our aims were to determine expression and activity levels of the hydrogen peroxide-reducing enzyme catalase in MS grey matter (GM). In MS GM, a catalase enzyme activity was elevated compared to control GM. We measured catalase protein expression by immune dot-blotting and catalase mRNA by a real-time polymerase chain reaction (RT-PCR). Protein analysis studies showed a strong positive correlation between catalase and microglial marker IBA-1 in MS GM. In addition, calibration of catalase mRNA level with reference to the microglial-specific transcript AIF-1 revealed an increase in this transcript in MS. This was reflected by the extent of HLA-DR immunolabeling in MS GM which was significantly elevated compared to control GM. Collectively, these observations provide evidence that microglial catalase activity is elevated in MS grey matter and may be an important endogenous anti-oxidant defence mechanism in MS. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

    Science.gov (United States)

    Parker, Lindsay M; Damanhuri, Hanafi A; Fletcher, Sophie P S; Goodchild, Ann K

    2015-04-16

    Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Diffusion tensor MRI tractography reveals increased fractional anisotropy (FA) in arcuate fasciculus following music-cued motor training.

    Science.gov (United States)

    Moore, Emma; Schaefer, Rebecca S; Bastin, Mark E; Roberts, Neil; Overy, Katie

    2017-08-01

    Auditory cues are frequently used to support movement learning and rehabilitation, but the neural basis of this behavioural effect is not yet clear. We investigated the microstructural neuroplasticity effects of adding musical cues to a motor learning task. We hypothesised that music-cued, left-handed motor training would increase fractional anisotropy (FA) in the contralateral arcuate fasciculus, a fibre tract connecting auditory, pre-motor and motor regions. Thirty right-handed participants were assigned to a motor learning condition either with (Music Group) or without (Control Group) musical cues. Participants completed 20minutes of training three times per week over four weeks. Diffusion tensor MRI and probabilistic neighbourhood tractography identified FA, axial (AD) and radial (RD) diffusivity before and after training. Results revealed that FA increased significantly in the right arcuate fasciculus of the Music group only, as hypothesised, with trends for AD to increase and RD to decrease, a pattern of results consistent with activity-dependent increases in myelination. No significant changes were found in the left ipsilateral arcuate fasciculus of either group. This is the first evidence that adding musical cues to movement learning can induce rapid microstructural change in white matter pathways in adults, with potential implications for therapeutic clinical practice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Sequencing the extrachromosomal circular mobilome reveals retrotransposon activity in plants.

    Directory of Open Access Journals (Sweden)

    Sophie Lanciano

    2017-02-01

    Full Text Available Retrotransposons are mobile genetic elements abundant in plant and animal genomes. While efficiently silenced by the epigenetic machinery, they can be reactivated upon stress or during development. Their level of transcription not reflecting their transposition ability, it is thus difficult to evaluate their contribution to the active mobilome. Here we applied a simple methodology based on the high throughput sequencing of extrachromosomal circular DNA (eccDNA forms of active retrotransposons to characterize the repertoire of mobile retrotransposons in plants. This method successfully identified known active retrotransposons in both Arabidopsis and rice material where the epigenome is destabilized. When applying mobilome-seq to developmental stages in wild type rice, we identified PopRice as a highly active retrotransposon producing eccDNA forms in the wild type endosperm. The mobilome-seq strategy opens new routes for the characterization of a yet unexplored fraction of plant genomes.

  12. Sequencing the extrachromosomal circular mobilome reveals retrotransposon activity in plants.

    Science.gov (United States)

    Lanciano, Sophie; Carpentier, Marie-Christine; Llauro, Christel; Jobet, Edouard; Robakowska-Hyzorek, Dagmara; Lasserre, Eric; Ghesquière, Alain; Panaud, Olivier; Mirouze, Marie

    2017-02-01

    Retrotransposons are mobile genetic elements abundant in plant and animal genomes. While efficiently silenced by the epigenetic machinery, they can be reactivated upon stress or during development. Their level of transcription not reflecting their transposition ability, it is thus difficult to evaluate their contribution to the active mobilome. Here we applied a simple methodology based on the high throughput sequencing of extrachromosomal circular DNA (eccDNA) forms of active retrotransposons to characterize the repertoire of mobile retrotransposons in plants. This method successfully identified known active retrotransposons in both Arabidopsis and rice material where the epigenome is destabilized. When applying mobilome-seq to developmental stages in wild type rice, we identified PopRice as a highly active retrotransposon producing eccDNA forms in the wild type endosperm. The mobilome-seq strategy opens new routes for the characterization of a yet unexplored fraction of plant genomes.

  13. Sequencing the extrachromosomal circular mobilome reveals retrotransposon activity in plants

    OpenAIRE

    Lanciano, Sophie; Carpentier, M. C.; Llauro, C.; Jobet, E.; Robakowska-Hyzorek, D.; Lasserre, E.; Ghesquière, Alain; Panaud, O.; Mirouze, Marie

    2017-01-01

    Retrotransposons are mobile genetic elements abundant in plant and animal genomes. While efficiently silenced by the epigenetic machinery, they can be reactivated upon stress or during development. Their level of transcription not reflecting their transposition ability, it is thus difficult to evaluate their contribution to the active mobilome. Here we applied a simple methodology based on the high throughput sequencing of extrachromosomal circular DNA (eccDNA) forms of active retrotransposon...

  14. School-Based Health Promotion Initiative Increases Children's Physical Activity

    Science.gov (United States)

    Cluss, Patricia; Lorigan, Devin; Kinsky, Suzanne; Nikolajski, Cara; McDermott, Anne; Bhat, Kiran B.

    2016-01-01

    Background: Childhood obesity increases health risk, and modest physical activity can impact that risk. Schools have an opportunity to help children become more active. Purpose: This study implemented a program offering extra school-day activity opportunities in a rural school district where 37% of students were obese or overweight in 2005 and…

  15. Anthropogenic Increase Of Soil Erosion In The Gangetic Plain Revealed By Geochemical Budget Of Erosion

    Science.gov (United States)

    Galy, V.; France-Lanord, C.; Galy, A.; Gaillardet, J.

    2007-12-01

    Himalaya. Based on the average composition of the suspended load and of floodplain soils, we estimate that 250x106 t/yr i.e. 5 t/ha/yr is eroded from soil surfaces of the Ganga floodplain. This enhanced soil erosion is likely triggered by intense deforestation and change in land use due to increasing human activity in the basin.

  16. Active Tectonics Revealed by River Profiles along the Puqu Fault

    Directory of Open Access Journals (Sweden)

    Ping Lu

    2015-04-01

    Full Text Available The Puqu Fault is situated in Southern Tibet. It is influenced by the eastward extrusion of Northern Tibet and carries the clockwise rotation followed by the southward extrusion. Thus, the Puqu Fault is bounded by the principal dynamic zones and the tectonic evolution remains active alongside. This study intends to understand the tectonic activity in the Puqu Fault Region from the river profiles obtained from the remotely sensed satellite imagery. A medium resolution Digital Elevation Model (DEM, 20 m was generated from an Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER stereo pair of images and the stream network in this region was extracted from this DEM. The indices of slope and drainage area were subsequently calculated from this ASTER DEM. Based on the stream power law, the area-slope plots of the streams were delineated to derive the indices of channel concavity and steepness, which are closely related to tectonic activity. The results show the active tectonics varying significantly along the Puqu Fault, although the potential influence of glaciations may exist. These results are expected to be useful for a better understanding of tectonic evolution in Southeastern Tibet.

  17. Microfabricated microbial fuel cell arrays reveal electrochemically active microbes.

    Directory of Open Access Journals (Sweden)

    Huijie Hou

    Full Text Available Microbial fuel cells (MFCs are remarkable "green energy" devices that exploit microbes to generate electricity from organic compounds. MFC devices currently being used and studied do not generate sufficient power to support widespread and cost-effective applications. Hence, research has focused on strategies to enhance the power output of the MFC devices, including exploring more electrochemically active microbes to expand the few already known electricigen families. However, most of the MFC devices are not compatible with high throughput screening for finding microbes with higher electricity generation capabilities. Here, we describe the development of a microfabricated MFC array, a compact and user-friendly platform for the identification and characterization of electrochemically active microbes. The MFC array consists of 24 integrated anode and cathode chambers, which function as 24 independent miniature MFCs and support direct and parallel comparisons of microbial electrochemical activities. The electricity generation profiles of spatially distinct MFC chambers on the array loaded with Shewanella oneidensis MR-1 differed by less than 8%. A screen of environmental microbes using the array identified an isolate that was related to Shewanella putrefaciens IR-1 and Shewanella sp. MR-7, and displayed 2.3-fold higher power output than the S. oneidensis MR-1 reference strain. Therefore, the utility of the MFC array was demonstrated.

  18. Metatranscriptomics reveals overall active bacterial composition in caries lesions

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    Aurea Simón-Soro

    2014-10-01

    Full Text Available Background: Identifying the microbial species in caries lesions is instrumental to determine the etiology of dental caries. However, a significant proportion of bacteria in carious lesions have not been cultured, and the use of molecular methods has been limited to DNA-based approaches, which detect both active and inactive or dead microorganisms. Objective: To identify the RNA-based, metabolically active bacterial composition of caries lesions at different stages of disease progression in order to provide a list of potential etiological agents of tooth decay. Design: Non-cavitated enamel caries lesions (n=15 and dentin caries lesions samples (n=12 were collected from 13 individuals. RNA was extracted and cDNA was constructed, which was used to amplify the 16S rRNA gene. The resulting 780 bp polymerase chain reaction products were pyrosequenced using Titanium-plus chemistry, and the sequences obtained were used to determine the bacterial composition. Results: A mean of 4,900 sequences of the 16S rRNA gene with an average read length of 661 bp was obtained per sample, giving a comprehensive view of the active bacterial communities in caries lesions. Estimates of bacterial diversity indicate that the microbiota of cavities is highly complex, each sample containing between 70 and 400 metabolically active species. The composition of these bacterial consortia varied among individuals and between caries lesions of the same individuals. In addition, enamel and dentin lesions had a different bacterial makeup. Lactobacilli were found almost exclusively in dentin cavities. Streptococci accounted for 40% of the total active community in enamel caries, and 20% in dentin caries. However, Streptococcus mutans represented only 0.02–0.73% of the total bacterial community. Conclusions: The data indicate that the etiology of dental caries is tissue dependent and that the disease has a clear polymicrobial origin. The low proportion of mutans streptococci

  19. Shared memories reveal shared structure in neural activity across individuals

    Science.gov (United States)

    Chen, J.; Leong, Y.C.; Honey, C.J.; Yong, C.H.; Norman, K.A.; Hasson, U.

    2016-01-01

    Our lives revolve around sharing experiences and memories with others. When different people recount the same events, how similar are their underlying neural representations? Participants viewed a fifty-minute movie, then verbally described the events during functional MRI, producing unguided detailed descriptions lasting up to forty minutes. As each person spoke, event-specific spatial patterns were reinstated in default-network, medial-temporal, and high-level visual areas. Individual event patterns were both highly discriminable from one another and similar between people, suggesting consistent spatial organization. In many high-order areas, patterns were more similar between people recalling the same event than between recall and perception, indicating systematic reshaping of percept into memory. These results reveal the existence of a common spatial organization for memories in high-level cortical areas, where encoded information is largely abstracted beyond sensory constraints; and that neural patterns during perception are altered systematically across people into shared memory representations for real-life events. PMID:27918531

  20. Functional imaging reveals movement preparatory activity in the vegetative state

    Directory of Open Access Journals (Sweden)

    Tristan A Bekinschtein

    2011-01-01

    Full Text Available The Vegetative State (VS is characterized by the absence of awareness of self or the environment and preserved autonomic functions. The diagnosis relies critically on the lack of consistent signs of purposeful behavior in response to external stimulation. Yet, given that patients with disorders of consciousness often exhibit fragmented movement patterns, voluntary actions may go unnoticed. Here we designed a simple motor paradigm that could potentially detect residual conscious awareness in VS patients with mild to severe brain damage by examining the neural correlates of motor preparation in response to verbal commands. Twenty-four patients who met the diagnostic criteria for VS were recruited for this study. Eleven of these patients showing preserved auditory evoked potentials underwent functional magnetic resonance imaging (fMRI to test for basic speech processing. Five of these patients, who showed word related activity, were included in a second fMRI study aimed at detecting functional changes in premotor cortex elicited by specific verbal instructions to move either their left or their right hand. Despite the lack of overt muscle activity, two patients out of five activated the dorsal premotor cortex contralateral to the instructed hand, consistent with movement preparation. Given that movement preparation in response to a motor command is a sign of purposeful behavior, our results are consistent with residual conscious awareness in these patients. We believe that the identification of positive results with fMRI using this simple task, may complement the clinical assessment by helping attain a more precise diagnosis in patients with disorders of consciousness.

  1. Activities on Facebook reveal the depressive state of users.

    Science.gov (United States)

    Park, Sungkyu; Lee, Sang Won; Kwak, Jinah; Cha, Meeyoung; Jeong, Bumseok

    2013-10-01

    As online social media have become prominent, much effort has been spent on identifying users with depressive symptoms in order to aim at early diagnosis, treatment, and even prevention by using various online social media. In this paper, we focused on Facebook to discern any correlations between the platform's features and users' depressive symptoms. This work may be helpful in trying to reach and detect large numbers of depressed individuals more easily. Our goal was to develop a Web application and identify depressive symptom-related features from users of Facebook, a popular social networking platform. 55 Facebook users (male=40, female=15, mean age 24.43, SD 3.90) were recruited through advertisement fliers distributed to students in a large university in Korea. Using EmotionDiary, the Facebook application we developed, we evaluated depressive symptoms using the Center for Epidemiological Studies-Depression (CES-D) scale. We also provided tips and facts about depression to participants and measured their responses using EmotionDiary. To identify the Facebook features related to depression, correlation analyses were performed between CES-D and participants' responses to tips and facts or Facebook social features. Last, we interviewed depressed participants (CES-D≥25) to assess their depressive symptoms by a psychiatrist. Facebook activities had predictive power in distinguishing depressed and nondepressed individuals. Participants' response to tips and facts, which can be explained by the number of app tips viewed and app points, had a positive correlation (P=.04 for both cases), whereas the number of friends and location tags had a negative correlation with the CES-D scale (P=.08 and P=.045 respectively). Furthermore, in finding group differences in Facebook social activities, app tips viewed and app points resulted in significant differences (P=.01 and P=.03 respectively) between probably depressed and nondepressed individuals. Our results using Emotion

  2. Expected Increase of Activity of Eta Aquariids Meteor Shower

    Science.gov (United States)

    Kulikova, N. V.; Chepurova, V. M.

    2018-04-01

    Analysis of the results of modeling disintegration of Comet 1P/Halley after its flare in 1991 has allowed us to predict an increase of the activity of the associated Eta Aquariids meteor shower in April-May 2018.

  3. Casein phosphopeptides drastically increase the secretion of extracellular proteins in Aspergillus awamori. Proteomics studies reveal changes in the secretory pathway.

    Science.gov (United States)

    Kosalková, Katarina; García-Estrada, Carlos; Barreiro, Carlos; Flórez, Martha G; Jami, Mohammad S; Paniagua, Miguel A; Martín, Juan F

    2012-01-10

    The secretion of heterologous animal proteins in filamentous fungi is usually limited by bottlenecks in the vesicle-mediated secretory pathway. Using the secretion of bovine chymosin in Aspergillus awamori as a model, we found a drastic increase (40 to 80-fold) in cells grown with casein or casein phosphopeptides (CPPs). CPPs are rich in phosphoserine, but phosphoserine itself did not increase the secretion of chymosin. The stimulatory effect is reduced about 50% using partially dephosphorylated casein and is not exerted by casamino acids. The phosphopeptides effect was not exerted at transcriptional level, but instead, it was clearly observed on the secretion of chymosin by immunodetection analysis. Proteomics studies revealed very interesting metabolic changes in response to phosphopeptides supplementation. The oxidative metabolism was reduced, since enzymes involved in fermentative processes were overrepresented. An oxygen-binding hemoglobin-like protein was overrepresented in the proteome following phosphopeptides addition. Most interestingly, the intracellular pre-protein enzymes, including pre-prochymosin, were depleted (most of them are underrepresented in the intracellular proteome after the addition of CPPs), whereas the extracellular mature form of several of these secretable proteins and cell-wall biosynthetic enzymes was greatly overrepresented in the secretome of phosphopeptides-supplemented cells. Another important 'moonlighting' protein (glyceraldehyde-3-phosphate dehydrogenase), which has been described to have vesicle fusogenic and cytoskeleton formation modulating activities, was clearly overrepresented in phosphopeptides-supplemented cells. In summary, CPPs cause the reprogramming of cellular metabolism, which leads to massive secretion of extracellular proteins.

  4. Increased sternocleidomastoid, but not trapezius, muscle activity in response to increased chewing load.

    Science.gov (United States)

    Häggman-Henrikson, Birgitta; Nordh, Erik; Eriksson, Per-Olof

    2013-10-01

    Previous findings, during chewing, that boluses of larger size and harder texture result in larger amplitudes of both mandibular and head-neck movements suggest a relationship between increased chewing load and incremental recruitment of jaw and neck muscles. The present report evaluated jaw (masseter and digastric) and neck [sternocleidomastoid (SCM) and trapezius] muscle activity during the chewing of test foods of different sizes and textures by 10 healthy subjects. Muscle activity was recorded by surface electromyography and simultaneous mandibular and head movements were recorded using an optoelectronic technique. Each subject performed continuous jaw-opening/jaw-closing movements whilst chewing small and large boluses of chewing gum and rubber silicone (Optosil). For jaw opening/jaw closing without a bolus, SCM activity was recorded for jaw opening concomitantly with digastric activity. During chewing, SCM activity was recorded for jaw closing concomitantly with masseter activity. Trapezius activity was present in some, but not all, cycles. For the masseter and SCM muscles, higher activity was seen with larger test foods, suggesting increased demand and recruitment of these muscles in response to an increased chewing load. This result reinforces the previous notion of a close functional connection between the jaw and the neck motor systems in jaw actions and has scientific and clinical significance for studying jaw function and dysfunction. © 2013 Eur J Oral Sci.

  5. Jealousy increased by induced relative left frontal cortical activity.

    Science.gov (United States)

    Kelley, Nicholas J; Eastwick, Paul W; Harmon-Jones, Eddie; Schmeichel, Brandon J

    2015-10-01

    Asymmetric frontal cortical activity may be one key to the process linking social exclusion to jealous feelings. The current research examined the causal role of asymmetric frontal brain activity in modulating jealousy in response to social exclusion. Transcranial direct-current stimulation (tDCS) over the frontal cortex to manipulate asymmetric frontal cortical activity was combined with a modified version of the Cyberball paradigm designed to induce jealousy. After receiving 15 min of tDCS, participants were excluded by a desired partner and reported how jealous they felt. Among individuals who were excluded, tDCS to increase relative left frontal cortical activity caused greater levels of self-reported jealousy compared to tDCS to increase relative right frontal cortical activity or sham stimulation. Limitations concerning the specificity of this effect and implications for the role of the asymmetric prefrontal cortical activity in motivated behaviors are discussed. (c) 2015 APA, all rights reserved).

  6. High-Elevation Sierra Nevada Conifers Reveal Increasing Reliance on Snow Water with Changing Climate

    Science.gov (United States)

    Lepley, K. S.; Meko, D. M.; Touchan, R.; Shamir, E.; Graham, R.

    2017-12-01

    Snowpack in the Sierra Nevada Mountains accounts for around one third of California's water supply. Melting snow can provide water into dry summer months characteristic of the region's Mediterranean climate. As climate changes, understanding patterns of snowpack, snowmelt, and biological response are critical in this region of agricultural, recreational, and ecological value. Tree rings can act as proxy records to inform scientists and resource managers of past climate variability where instrumental data is unavailable. Here we investigate relationships between tree rings of high-elevation, snow-adapted conifer trees (Tsuga mertensiana, Abies magnifica) and April 1st snow-water equivalent (SWE) in the northern Sierra Nevada Mountains. The 1st principal component of 29 highly correlated regional SWE time series was modeled using multiple linear regression of four tree-ring chronologies including two lagged chronologies. Split-period verification analysis of this model revealed poor predictive skill in the early half (1929 - 1966) of the calibration period (1929 - 2003). Further analysis revealed a significant (p time. Snow water is becoming a more limiting resource to tree growth as average temperatures rise and the hydrologic regime shifts. These results highlight the need for resource managers and policy makers to consider that biological response to climate is not static.

  7. Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia

    NARCIS (Netherlands)

    Olde Loohuis, Loes M.; Mangul, Serghei; Ori, Anil P.S.; Jospin, Guillaume; Koslicki, David; Yang, Harry Taegyun; Wu, Timothy; Boks, Marco P.; Lomen-Hoerth, Catherine; Wiedau-Pazos, Martina; Cantor, Rita M.; Vos, De Willem M.; Kahn, René S.; Eskin, Eleazar; Ophoff, Roel A.

    2018-01-01

    The role of the human microbiome in health and disease is increasingly appreciated. We studied the composition of microbial communities present in blood across 192 individuals, including healthy controls and patients with three disorders affecting the brain: schizophrenia, amyotrophic lateral

  8. Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

    Science.gov (United States)

    Knight, Jason S.; Meng, He; Coit, Patrick; Yalavarthi, Srilakshmi; Sule, Gautam; Gandhi, Alex A.; Grenn, Robert C.; Mazza, Levi F.; Ali, Ramadan A.; Renauer, Paul; Wren, Jonathan D.; Bockenstedt, Paula L.; Wang, Hui; Eitzman, Daniel T.; Sawalha, Amr H.

    2017-01-01

    Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophils — neutrophil extracellular traps (NETs), in particular — in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava. In patients, APS neutrophils demonstrated a proinflammatory signature with overexpression of genes relevant to IFN signaling, cellular defense, and intercellular adhesion. For in vivo studies, we focused on P-selectin glycoprotein ligand-1 (PSGL-1), a key adhesion molecule overexpressed in APS neutrophils. The introduction of APS IgG (as compared with control IgG) markedly potentiated thrombosis in WT mice, but not PSGL-1–KOs. PSGL-1 deficiency was also associated with reduced leukocyte vessel wall adhesion and NET formation. The thrombosis phenotype was restored in PSGL-1–deficient mice by infusion of WT neutrophils, while an anti–PSGL-1 monoclonal antibody inhibited APS IgG–mediated thrombosis in WT mice. PSGL-1 represents a potential therapeutic target in APS. PMID:28931754

  9. Building a Better Mousetrap (Exergame) to Increase Youth Physical Activity

    NARCIS (Netherlands)

    Baranowski, Tom; Maddison, Ralph; Maloney, Ann; Medina, Ernie; Simons, Monique

    Although exergames have been demonstrated to induce moderate levels of physical activity (PA) if played as designed, there is conflicting evidence on use of exergaming leading to increased habitual PA. Exergames have increased PA in some home and school studies, but not others. Exergames have been

  10. Increasing physical activity through mobile device interventions: A systematic review.

    Science.gov (United States)

    Muntaner, Adrià; Vidal-Conti, Josep; Palou, Pere

    2016-09-01

    Physical inactivity is a health problem that affects people worldwide and has been identified as the fourth largest risk factor for overall mortality (contributing to 6% of deaths globally). Many researchers have tried to increase physical activity levels through traditional methods without much success. Thus, many researchers are turning to mobile technology as an emerging method for changing health behaviours. This systematic review sought to summarise and update the existing scientific literature on increasing physical activity through mobile device interventions, taking into account the methodological quality of the studies. The articles were identified by searching the PubMed, SCOPUS and SPORTDiscus databases for studies published between January 2003 and December 2013. Studies investigating efforts to increase physical activity through mobile phone or even personal digital assistant interventions were included. The search results allowed the inclusion of 11 studies that gave rise to 12 publications. Six of the articles included in this review reported significant increases in physical activity levels. The number of studies using mobile devices for interventions has increased exponentially in the last few years, but future investigations with better methodological quality are needed to draw stronger conclusions regarding how to increase physical activity through mobile device interventions. © The Author(s) 2015.

  11. The impact of motivational interventions for increasing physical activity

    Directory of Open Access Journals (Sweden)

    Aneci Sobral Rocha

    2010-03-01

    Full Text Available Objective: To assess whether incentives for practicing regular physical activities in fact help raising the frequency of exercising. Methods: Male and female subjects undergoing two to three assessments in the Check-Up Unit of Hospital Israelita Albert Einstein (HIAE were evaluated by noting any increase in levels of physical activity, improvements in mean metabolic unit numbers, and the sensitization index. The International Physical Activity Questionnaire was applied to assess the sample. Results: There were 1,879 subjects – 1,559 (83% males and 320 (17% females – aged 20 to 76 years (mean age = 45.8 years, standard deviation ± 8.8 who underwent a Continued Health Review at the Center for Preventive Medicine of the HIAE, Check-Up Unit, Jardins. Initially, over half of the sample was insufficiently active (sedentary or poorly active; there were more women than men in this group. After the health review, most subjects increased their level of physical activity; this increase was higher among women. Males encouraged three times to exercising showed better results (increased level of physical activity as compared to males encouraged twice for exercising. The best results in females were found in the group that went through two evaluations. This result is due to the fact that the sample of females comprising the group that received incentives on three occasions was small. This was also the only group that showed no increase in mean metabolic units. The sensitization index assessment in the overall sample was very satisfactory, as the expected results were achieved. Conclusions: These results show that motivational interventions are effective for raising the level of physical activity. We concluded that to encourage the practice of regular physical activity through information programs about its health benefits is very important.

  12. Sweet Potato Value Chain Analysis Reveals Opportunities for Increased Income and Food Security in Northern Ghana

    Directory of Open Access Journals (Sweden)

    Issah Sugri

    2017-01-01

    Full Text Available Sweet potato has gained prominence due to its ability to adapt to wide production ecologies and yield response to minimal external inputs. Orange-fleshed cultivars in particular have immense potential to improve household income and nutrition in sub-Saharan Africa. However, the sweet potato value chain (SPVC is not well-developed in many producing countries. The study was conducted in two regions to characterize the production operations as well as identify opportunities to propel the SPVC in Northern Ghana. Data were collected using mixed methods including structured questionnaires via face-to-face interviews. Analysis of strengths, weaknesses, opportunities, and threats (SWOT was conducted at multistakeholder platforms with different actors. Gross margin profit and benefit-cost ratios were determined by using six cost variables. Overall, the industry was largely a fresh produce market, targeting food vendors, processors, and direct selling to wholesalers, retailers, and household consumers. The SWOT analysis revealed wide-ranging opportunities including favourable production ecologies, processing options, and insatiable local and international markets. The institutional actors need to network the primary actors to synergistically operate with a collective profit motive. The most prioritized production constraints such as access to seed, cost of chemical fertilizer, short shelf-life, field pests and diseases, and declining soil fertility should be addressed.

  13. Active sensing associated with spatial learning reveals memory-based attention in an electric fish.

    Science.gov (United States)

    Jun, James J; Longtin, André; Maler, Leonard

    2016-05-01

    Active sensing behaviors reveal what an animal is attending to and how it changes with learning. Gymnotus sp, a gymnotiform weakly electric fish, generates an electric organ discharge (EOD) as discrete pulses to actively sense its surroundings. We monitored freely behaving gymnotid fish in a large dark "maze" and extracted their trajectories and EOD pulse pattern and rate while they learned to find food with electrically detectable landmarks as cues. After training, they more rapidly found food using shorter, more stereotyped trajectories and spent more time near the food location. We observed three forms of active sensing: sustained high EOD rates per unit distance (sampling density), transient large increases in EOD rate (E-scans) and stereotyped scanning movements (B-scans) were initially strong at landmarks and food, but, after learning, intensified only at the food location. During probe (no food) trials, after learning, the fish's search area and intense active sampling was still centered on the missing food location, but now also increased near landmarks. We hypothesize that active sensing is a behavioral manifestation of attention and essential for spatial learning; the fish use spatial memory of landmarks and path integration to reach the expected food location and confine their attention to this region. Copyright © 2016 the American Physiological Society.

  14. Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia.

    Directory of Open Access Journals (Sweden)

    Yoshifumi Abe

    2017-04-01

    Full Text Available Diffusion functional MRI (DfMRI reveals neuronal activation even when neurovascular coupling is abolished, contrary to blood oxygenation level-dependent (BOLD functional MRI (fMRI. Here, we show that the water apparent diffusion coefficient (ADC derived from DfMRI increased in specific rat brain regions under anesthetic conditions, reflecting the decreased neuronal activity observed with local field potentials (LFPs, especially in regions involved in wakefulness. In contrast, BOLD signals showed nonspecific changes, reflecting systemic effects of the anesthesia on overall brain hemodynamics status. Electrical stimulation of the central medial thalamus nucleus (CM exhibiting this anesthesia-induced ADC increase led the animals to transiently wake up. Infusion in the CM of furosemide, a specific neuronal swelling blocker, led the ADC to increase further locally, although LFP activity remained unchanged, and increased the current threshold awakening the animals under CM electrical stimulation. Oppositely, induction of cell swelling in the CM through infusion of a hypotonic solution (-80 milliosmole [mOsm] artificial cerebrospinal fluid [aCSF] led to a local ADC decrease and a lower current threshold to wake up the animals. Strikingly, the local ADC changes produced by blocking or enhancing cell swelling in the CM were also mirrored remotely in areas functionally connected to the CM, such as the cingulate and somatosensory cortex. Together, those results strongly suggest that neuronal swelling is a significant mechanism underlying DfMRI.

  15. Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue.

    Directory of Open Access Journals (Sweden)

    Monique Ramos de Oliveira Trugilho

    2017-05-01

    Full Text Available Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet

  16. [Increase of physical activity by improvement of the nutritional status].

    Science.gov (United States)

    Torún, B

    1989-09-01

    Physical activity is affected by nutritional modifications and, in turn, influences growth, cognition, social behavior, work performance and other functions. Studies in preschool children showed that: 1. A decrease in energy intake during four to seven days reduced the time allocated to energy-demanding activities and increased sedentary activities. 2. Children with mild weight deficit were more sedentary than well-nourished counterparts. 3. Children became more active when nutritional status improved. 4. A 10% reduction in energy intake reduced total energy expenditure by 15% without affecting weight gain nor basal metabolism. Studies of men working in non-mechanized agriculture showed that: 1. Dietary improvements led to faster salaried work, reduction of napping time and greater physical activity after work. 2. An increase in energy intake increased total daily energy expenditure, tending to maintain energy balance and relatively stable body weight within the cyclic variations of the agricultural year. 3. Food supplementation did not necessarily improve productivity. Other labor incentives without dietary improvements increased energy expenditure during working hours, which resulted in weight loss. In conclusion, good health and nutrition provide the biological basis for adequate physical activity that may improve cognitive development, social interactions, economic productivity and the quality of life of an individual or a population, but other incentives are required for the optimal expression of that biologic potential.

  17. Purification of reversibly oxidized proteins (PROP reveals a redox switch controlling p38 MAP kinase activity.

    Directory of Open Access Journals (Sweden)

    Dennis J Templeton

    2010-11-01

    Full Text Available Oxidation of cysteine residues of proteins is emerging as an important means of regulation of signal transduction, particularly of protein kinase function. Tools to detect and quantify cysteine oxidation of proteins have been a limiting factor in understanding the role of cysteine oxidation in signal transduction. As an example, the p38 MAP kinase is activated by several stress-related stimuli that are often accompanied by in vitro generation of hydrogen peroxide. We noted that hydrogen peroxide inhibited p38 activity despite paradoxically increasing the activating phosphorylation of p38. To address the possibility that cysteine oxidation may provide a negative regulatory effect on p38 activity, we developed a biochemical assay to detect reversible cysteine oxidation in intact cells. This procedure, PROP, demonstrated in vivo oxidation of p38 in response to hydrogen peroxide and also to the natural inflammatory lipid prostaglandin J2. Mutagenesis of the potential target cysteines showed that oxidation occurred preferentially on residues near the surface of the p38 molecule. Cysteine oxidation thus controls a functional redox switch regulating the intensity or duration of p38 activity that would not be revealed by immunodetection of phosphoprotein commonly interpreted as reflective of p38 activity.

  18. Magnetoencephalography Reveals a Widespread Increase in Network Connectivity in Idiopathic/Genetic Generalized Epilepsy.

    Directory of Open Access Journals (Sweden)

    Adham Elshahabi

    Full Text Available Idiopathic/genetic generalized epilepsy (IGE/GGE is characterized by seizures, which start and rapidly engage widely distributed networks, and result in symptoms such as absences, generalized myoclonic and primary generalized tonic-clonic seizures. Although routine magnetic resonance imaging is apparently normal, many studies have reported structural alterations in IGE/GGE patients using diffusion tensor imaging and voxel-based morphometry. Changes have also been reported in functional networks during generalized spike wave discharges. However, network function in the resting-state without epileptiforme discharges has been less well studied. We hypothesize that resting-state networks are more representative of the underlying pathophysiology and abnormal network synchrony. We studied functional network connectivity derived from whole-brain magnetoencephalography recordings in thirteen IGE/GGE and nineteen healthy controls. Using graph theoretical network analysis, we found a widespread increase in connectivity in patients compared to controls. These changes were most pronounced in the motor network, the mesio-frontal and temporal cortex. We did not, however, find any significant difference between the normalized clustering coefficients, indicating preserved gross network architecture. Our findings suggest that increased resting state connectivity could be an important factor for seizure spread and/or generation in IGE/GGE, and could serve as a biomarker for the disease.

  19. Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells

    International Nuclear Information System (INIS)

    Dietz, Marina S; Haße, Daniel; Ferraris, Davide M; Göhler, Antonia; Niemann, Hartmut H; Heilemann, Mike

    2013-01-01

    The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.

  20. Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux

    NARCIS (Netherlands)

    Vrins, Carlos L. J.; van der Velde, Astrid E.; van den Oever, Karin; Levels, Johannes H. M.; Huet, Stephane; Elferink, Ronald P. J. Oude; Kuipers, Folkert; Groen, Albert K.

    2009-01-01

    Peroxisome proliferator-activated receptor delta (PPAR delta) is involved in regulation of energy homeostasis. Activation of PPAR delta markedly increases fecal neutral sterol secretion, the last step in reverse cholesterol transport. This phenomenon can neither be explained by increased

  1. Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux

    NARCIS (Netherlands)

    Vrins, Carlos L. J.; van der Velde, Astrid E.; van den Oever, Karin; Levels, Johannes H. M.; Huet, Stephane; Oude Elferink, Ronald P. J.; Kuipers, Folkert; Groen, Albert K.

    2009-01-01

    Peroxisome proliferator-activated receptor delta (PPARdelta) is involved in regulation of energy homeostasis. Activation of PPARdelta markedly increases fecal neutral sterol secretion, the last step in reverse cholesterol transport. This phenomenon can neither be explained by increased hepatobiliary

  2. The marine toxin, Yessotoxin, induces apoptosis and increases mitochondrial activity

    Directory of Open Access Journals (Sweden)

    Andrea Fernandez-Araujo

    2014-06-01

    Discussion: Colorimetric MTT assay is widely used as a viability measurement method (McHale and L., 1988;Chiba et al., 1998. But after YTX treatment, MTT assay had shown problems to detect a cell viability decrease. In this sense, in primary cardiac cell cultures, a false increment of the proliferation rate opposite to Sulforhodamine B assay (SRB results was reported after YTX treatment (Dell'Ovo et al., 2008. Also the same effect was obtained in different cancer cell lines after assaying anticancer therapies (Ulukaya et al., 2004. In our study, an increase in cell viability using MTT was observed when the number of cells was high, while by using the LDH assay a significant viability decrease was measured. In these conditions, YTX is activating extrinsic apoptosis cell death by increasing caspase 8 activity and caspase 3 levels. The explanation for this increase was found when the mitochondrial activity was quantified cell by cell in a cytometer. In these conditions a significant increment of mitochondrial activity was detected. Since the cell population is too high, the increase in mitochondrial activity that detects the MTT test disguised the decrease of signal due to the cell death and point to a false proliferation increase. In this sense, a mitochondrial activity decrease was observed after 48 hours YTX treatment in BE(2-M17 neuroblastoma cell line (Leira et al., 2002. However, this study was done in a microplate reader with a small number of cells (Leira et al., 2002. Therefore, to measure the viability by MTT assay is very important to take into account the number of cells per condition when the experiment is designed. Alternative assays, such as LDH test, independently of the direct mitochondrial activity, can be used.

  3. Casein phosphopeptides drastically increase the secretion of extracellular proteins in Aspergillus awamori. Proteomics studies reveal changes in the secretory pathway

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    Kosalková Katarina

    2012-01-01

    Full Text Available Abstract Background The secretion of heterologous animal proteins in filamentous fungi is usually limited by bottlenecks in the vesicle-mediated secretory pathway. Results Using the secretion of bovine chymosin in Aspergillus awamori as a model, we found a drastic increase (40 to 80-fold in cells grown with casein or casein phosphopeptides (CPPs. CPPs are rich in phosphoserine, but phosphoserine itself did not increase the secretion of chymosin. The stimulatory effect is reduced about 50% using partially dephosphorylated casein and is not exerted by casamino acids. The phosphopeptides effect was not exerted at transcriptional level, but instead, it was clearly observed on the secretion of chymosin by immunodetection analysis. Proteomics studies revealed very interesting metabolic changes in response to phosphopeptides supplementation. The oxidative metabolism was reduced, since enzymes involved in fermentative processes were overrepresented. An oxygen-binding hemoglobin-like protein was overrepresented in the proteome following phosphopeptides addition. Most interestingly, the intracellular pre-protein enzymes, including pre-prochymosin, were depleted (most of them are underrepresented in the intracellular proteome after the addition of CPPs, whereas the extracellular mature form of several of these secretable proteins and cell-wall biosynthetic enzymes was greatly overrepresented in the secretome of phosphopeptides-supplemented cells. Another important 'moonlighting' protein (glyceraldehyde-3-phosphate dehydrogenase, which has been described to have vesicle fusogenic and cytoskeleton formation modulating activities, was clearly overrepresented in phosphopeptides-supplemented cells. Conclusions In summary, CPPs cause the reprogramming of cellular metabolism, which leads to massive secretion of extracellular proteins.

  4. Physical activity increases survival after heart valve surgery

    DEFF Research Database (Denmark)

    Lund, K.; Sibilitz, Kirstine Lærum; Kikkenborg Berg, Selina

    2016-01-01

    physical activity levels 6-12 months after heart valve surgery and (1) survival, (2) hospital readmission 18-24 months after surgery and (3) participation in exercise-based cardiac rehabilitation. METHODS: Prospective cohort study with registry data from The CopenHeart survey, The Danish National Patient......OBJECTIVES: Increased physical activity predicts survival and reduces risk of readmission in patients with coronary heart disease. However, few data show how physical activity is associated with survival and readmission after heart valve surgery. Objective were to assess the association between...... Register and The Danish Civil Registration System of 742 eligible patients. Physical activity was quantified with the International Physical Activity Questionnaire and analysed using Kaplan-Meier analysis and Cox regression and logistic regression methods. RESULTS: Patients with a moderate to high physical...

  5. Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy.

    Science.gov (United States)

    West, Crystal; Zhang, Zheng; Ecker, Geoffrey; Masilamani, Shyama M E

    2010-11-01

    Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

  6. Increased cortical-limbic anatomical network connectivity in major depression revealed by diffusion tensor imaging.

    Directory of Open Access Journals (Sweden)

    Peng Fang

    Full Text Available Magnetic resonance imaging studies have reported significant functional and structural differences between depressed patients and controls. Little attention has been given, however, to the abnormalities in anatomical connectivity in depressed patients. In the present study, we aim to investigate the alterations in connectivity of whole-brain anatomical networks in those suffering from major depression by using machine learning approaches. Brain anatomical networks were extracted from diffusion magnetic resonance images obtained from both 22 first-episode, treatment-naive adults with major depressive disorder and 26 matched healthy controls. Using machine learning approaches, we differentiated depressed patients from healthy controls based on their whole-brain anatomical connectivity patterns and identified the most discriminating features that represent between-group differences. Classification results showed that 91.7% (patients=86.4%, controls=96.2%; permutation test, p<0.0001 of subjects were correctly classified via leave-one-out cross-validation. Moreover, the strengths of all the most discriminating connections were increased in depressed patients relative to the controls, and these connections were primarily located within the cortical-limbic network, especially the frontal-limbic network. These results not only provide initial steps toward the development of neurobiological diagnostic markers for major depressive disorder, but also suggest that abnormal cortical-limbic anatomical networks may contribute to the anatomical basis of emotional dysregulation and cognitive impairments associated with this disease.

  7. Does physical activity increase the risk of unsafe sun exposure?

    Science.gov (United States)

    Jardine, Andrew; Bright, Margaret; Knight, Libby; Perina, Heather; Vardon, Paul; Harper, Catherine

    2012-04-01

    Recent increases in the prevalence of self-reported participation in physical activity are encouraging and beneficial for health overall. However, the implications for sun safety need to be considered, particularly in Australia, which has the highest incidence of skin cancer in the world. This study investigated the relationship between physical activity and sunburn to determine if there is a need for integration of sun safety in physical activity promotion. During the 2009/10 southern hemisphere summer, 7802 adults aged 18 to 74 years participated in a computer-assisted telephone interview survey which included a range of self-reported health measures including physical activity, sunburn, skin type, sun protection behaviour and demographic questions. Multivariate logistic regression modelling was undertaken to estimate the association between physical activity and sunburn. Those who reported doing any level of physical activity were significantly more likely to report having experienced sunburn in the past 12 months and on the last weekend, compared with those who did none, with the strongest association among those who undertook 7 hours or more. Each hour of physical activity was associated with a modest increase in the odds of experiencing sunburn in the previous 12 months (OR 1.02, 95% CI 1.010-1.037) and weekend (OR 1.04, 95% CI: 1.023-1.065), after adjusting for potential confounding variables. This study highlights the need for sun protection to be given more prominence in physical activity promotion in order to optimise health benefits without increasing the prevalence of sunburn and associated skin cancer risk.

  8. Texting to increase adolescent physical activity: Feasibility assessment

    Science.gov (United States)

    Feasibility trials assess whether a behavior change program warrants a definite trial evaluation. This paper reports the feasibility of an intervention consisting of Self Determination Theory-informed text messages, pedometers, and goal prompts to increase adolescent physical activity. A 4-group ran...

  9. Increased NTPDase Activity in Lymphocytes during Experimental Sepsis

    Science.gov (United States)

    Bertoncheli, Claudia de Mello; Zimmermann, Carine Eloise Prestes; Jaques, Jeandre Augusto dos Santos; Leal, Cláudio Alberto Martins; Ruchel, Jader Betsch; Rocha, Bruna Cipolatto; Pinheiro, Kelly de Vargas; Souza, Viviane do Carmo Gonçalves; Stainki, Daniel Roulim; Luz, Sônia Cristina Almeida; Schetinger, Maria Rosa Chitolina; Leal, Daniela Bitencourt Rosa

    2012-01-01

    We investigated in rats induced to sepsis the activity of ectonucleoside triphosphate diphosphohydrolase (NTPDase; CD39; E.C. 3.6.1.5), an enzyme involved in the modulation of immune responses. After 12 hours of surgery, lymphocytes were isolated from blood and NTPDase activity was determined. It was also performed the histology of kidney, liver, and lung. The results demonstrated an increase in the hydrolysis of adenosine-5′-triphosphate (ATP) (P 0.05). Histological analysis showed several morphological changes in the septic group, such as vascular congestion, necrosis, and infiltration of mononuclear cells. It is known that the intracellular milieu contains much more ATP nucleotides than the extracellular. In this context, the increased ATPasic activity was probably induced as a dynamic response to clean up the elevated ATP levels resulting from cellular death. PMID:22645477

  10. Does Physical Activity Increase Life Expectancy? A Review of the Literature

    Directory of Open Access Journals (Sweden)

    C. D. Reimers

    2012-01-01

    Full Text Available Physical activity reduces many major mortality risk factors including arterial hypertension, diabetes mellitus type 2, dyslipidemia, coronary heart disease, stroke, and cancer. All-cause mortality is decreased by about 30% to 35% in physically active as compared to inactive subjects. The purpose of this paper was to synthesize the literature on life expectancy in relation to physical activity. A systematic PubMed search on life expectancy in physically active and inactive individuals was performed. In addition, articles comparing life expectancy of athletes compared to that of nonathletes were reviewed. Results of 13 studies describing eight different cohorts suggest that regular physical activity is associated with an increase of life expectancy by 0.4 to 6.9 years. Eleven studies included confounding risk factors for mortality and revealed an increase in life expectancy by 0.4 to 4.2 years with regular physical activity. Eleven case control studies on life expectancy in former athletes revealed consistently greater life expectancy in aerobic endurance athletes but inconsistent results for other athletes. None of these studies considered confounding risk factors for mortality. In conclusion, while regular physical activity increases life expectancy, it remains unclear if high-intensity sports activities further increase life expectancy.

  11. Increased physical activity decreases periodontitis risk in men

    International Nuclear Information System (INIS)

    Merchant, Anwar T.; Pitiphat, Waranuch; Rimm, Eric B.; Joshipura, Kaumudi

    2003-01-01

    Background: Increased physical activity improves insulin sensitivity and glucose metabolism, and may therefore affect incidence of periodontitis. Methods: We studied the association of physical activity, walking and periodontitis in 39,461 male, US based, health professionals, 40-75 years old at baseline, more than half of whom were dentists, being followed up continuously since 1986. Participants were free of periodontitis, coronary heart disease and stroke at the start of follow-up. Physical activity and periodontitis were measured by validated questionnaires (expressed in metabolic equivalents - METs); the first report of professionally diagnosed periodontitis was considered a case. Results: Periodontitis risk decreased by 3% for every 10-MET increase in average physical activity after adjustment for age, smoking, diabetes, BMI, alcohol consumption and total calories (RR = 0.97; 95% CI: 0.95-0.99). The inverse trend remained significant in the categorical analysis. Compared to men in the lowest quintile of physical activity, those in the highest quintile had a 13% lower risk of periodontitis (RR = 0.87; 95% CI: 0.76-1.01, p-value, test for trend = 0.02). In a sub-sample of men with radiographs (n = 137) the physically active had less average bone loss (β = -0.29, p-value = 0.03) after multivariate adjustment compared to those inactive. Conclusions: In this large-scale prospective study, we found an inverse, linear association between sustained physical activity and periodontitis independent of known risk factors. The benefits of a physically active lifestyle may extend to periodontal health

  12. Project U-Turn: increasing active transportation in Jackson, Michigan.

    Science.gov (United States)

    TenBrink, David S; McMunn, Randall; Panken, Sarah

    2009-12-01

    Jackson, Michigan, is a medium-sized city suffering from a bad economy and obesity-related health issues. Nearly 20% of the 36,000 residents live below the poverty line. It is a relatively young city (median age of 30 years) with a mixed ethnicity (20% black, 73% white, 4% Hispanic). The city offers many structured, active recreational opportunities, but has not integrated physical activity into daily life. Project U-Turn aimed to increase active transportation (e.g., biking, walking, and transit use) through an integrated approach to Active Living by Design's community action model and the Michigan Safe Routes to School model. Resources were focused on active living promotions and programs; partnership meetings were the source of changes in policy and physical projects. Each initiative was designed to introduce each of the 5Ps (preparation, promotion, programs, policy, and physical projects) to build support for the partnership's overall work. The partnership collected snapshot data of community walking and biking behavior, percentage of students walking to school, participation in events and programs, and new physical projects. Jackson saw a vast improvement in physical infrastructure and policy and a related increase in walking and biking in the community. The project engaged in purposeful partnership building to implement effective programs and promotions that built support for policy and physical projects. Limited resources were best used by encouraging partners to contribute and coordinate activities using existing staff, funding, and resources. Jackson has seen a shift toward awareness of the benefits of active living on community health, economic development, and environmental awareness.

  13. Chemically modified carboxypeptidase Y with increased amidase activity

    International Nuclear Information System (INIS)

    Breddam, K.

    1984-01-01

    Treatment of carboxypeptidase Y with 14 C-iodoacetamide caused a drastic reduction in the peptidase activity towards FA-Phe-Leu-OH while the esterase activity towards FA-Phe-OMe, the amidase activity towards FA-Phe-NH 2 and the peptidyl amino acid amide hydrolase activity towards FA-Phe-Gly-NH 2 were much less affected. The loss of peptidase activity could be correlated with the incorporation of a single equivalent of reagent and it was demonstrated that the site of reaction was a methionyl residue, thus forming a sulfonium derivative. Analogous methionyl modifications were performed: carboxypeptidase Y modified with phenacylbromide hydrolysed substrates with bulky leaving groups in the P position, i.e. -OEt, -OBzl, -Gly-NH 2 ,-Gly-OH, and -Leu-OH, at reduced rates while substrates with small groups in that position, i.e. -OMe and -NH 2 , were hydrolysed with increased rates. These results indicate that the methionyl residue modified by phenacylbromide is located in the S binding site of the enzyme. Similar results were obtained with carboxypeptidase Y modified with m-nitrophen- acylbromide and p-nitrophenacylbromide. The increase in amidase activity and decrease in peptidyl amino acid amide hydrolase activity of carboxypeptidase Y following modification with phenacylbromide, m-nitrophenacylbromide, and p-nitrophenacylbromide was exploited in deamidation of peptide amides. These modified enzymes deamidated peptide amides with the exception of those containing a C-terminal glycyl or seryl residue in yields of 80-100% which is significantly higher than with unmodified carboxypeptidase Y. (author)

  14. Active learning increases student performance in science, engineering, and mathematics.

    Science.gov (United States)

    Freeman, Scott; Eddy, Sarah L; McDonough, Miles; Smith, Michelle K; Okoroafor, Nnadozie; Jordt, Hannah; Wenderoth, Mary Pat

    2014-06-10

    To test the hypothesis that lecturing maximizes learning and course performance, we metaanalyzed 225 studies that reported data on examination scores or failure rates when comparing student performance in undergraduate science, technology, engineering, and mathematics (STEM) courses under traditional lecturing versus active learning. The effect sizes indicate that on average, student performance on examinations and concept inventories increased by 0.47 SDs under active learning (n = 158 studies), and that the odds ratio for failing was 1.95 under traditional lecturing (n = 67 studies). These results indicate that average examination scores improved by about 6% in active learning sections, and that students in classes with traditional lecturing were 1.5 times more likely to fail than were students in classes with active learning. Heterogeneity analyses indicated that both results hold across the STEM disciplines, that active learning increases scores on concept inventories more than on course examinations, and that active learning appears effective across all class sizes--although the greatest effects are in small (n ≤ 50) classes. Trim and fill analyses and fail-safe n calculations suggest that the results are not due to publication bias. The results also appear robust to variation in the methodological rigor of the included studies, based on the quality of controls over student quality and instructor identity. This is the largest and most comprehensive metaanalysis of undergraduate STEM education published to date. The results raise questions about the continued use of traditional lecturing as a control in research studies, and support active learning as the preferred, empirically validated teaching practice in regular classrooms.

  15. Protein energy malnutrition increases arginase activity in monocytes and macrophages.

    Science.gov (United States)

    Corware, Karina; Yardley, Vanessa; Mack, Christopher; Schuster, Steffen; Al-Hassi, Hafid; Herath, Shanthi; Bergin, Philip; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Kropf, Pascale

    2014-01-01

    Protein energy malnutrition is commonly associated with immune dysfunctions and is a major factor in susceptibility to infectious diseases. In this study, we evaluated the impact of protein energy malnutrition on the capacity of monocytes and macrophages to upregulate arginase, an enzyme associated with immunosuppression and increased pathogen replication. Our results show that monocytes and macrophages are significantly increased in the bone marrow and blood of mice fed on a protein low diet. No alteration in the capacity of bone marrow derived macrophages isolated from malnourished mice to phagocytose particles, to produce the microbicidal molecule nitric oxide and to kill intracellular Leishmania parasites was detected. However, macrophages and monocytes from malnourished mice express significantly more arginase both in vitro and in vivo. Using an experimental model of visceral leishmaniasis, we show that following protein energy malnutrition, the increased parasite burden measured in the spleen of these mice coincided with increased arginase activity and that macrophages provide a more permissive environment for parasite growth. Taken together, these results identify a novel mechanism in protein energy malnutrition that might contributes to increased susceptibility to infectious diseases by upregulating arginase activity in myeloid cells.

  16. Modafinil enhances thalamocortical activity by increasing neuronal electrotonic coupling

    Science.gov (United States)

    Urbano, Francisco J.; Leznik, Elena; Llinás, Rodolfo R.

    2007-01-01

    Modafinil (Provigil, Modiodal), an antinarcoleptic and mood-enhancing drug, is shown here to sharpen thalamocortical activity and to increase electrical coupling between cortical interneurons and between nerve cells in the inferior olivary nucleus. After irreversible pharmacological block of connexin permeability (i.e., by using either 18β-glycyrrhetinic derivatives or mefloquine), modafinil restored electrotonic coupling within 30 min. It was further established that this restoration is implemented through a Ca2+/calmodulin protein kinase II-dependent step. PMID:17640897

  17. Increased activation in Broca's area after cognitive remediation in schizophrenia.

    Science.gov (United States)

    Vianin, Pascal; Urben, Sébastien; Magistretti, Pierre; Marquet, Pierre; Fornari, Eleonora; Jaugey, Laure

    2014-03-30

    Functional magnetic resonance imaging (fMRI) was used to measure changes in cerebral activity in patients with schizophrenia after participation in the Cognitive Remediation Program for Schizophrenia and other related disorders (RECOS). As RECOS therapists make use of problem-solving and verbal mediation techniques, known to be beneficial in the rehabilitation of dysexecutive syndromes, we expected an increased activation of frontal areas after remediation. Executive functioning and cerebral activation during a covert verbal fluency task were measured in eight patients with schizophrenia before (T1) and after (T2) 14 weeks of RECOS therapy. The same measures were recorded in eight patients with schizophrenia who did not participate in RECOS at the same intervals of time (TAU group). Increased activation in Broca's area, as well as improvements in performance of executive/frontal tasks, was observed after cognitive training. Metacognitive techniques of verbalization are hypothesized to be the main factor underlying the brain changes observed in the present study. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Using Technology to Increase Physical Activity in Health Profession Students

    Directory of Open Access Journals (Sweden)

    Mary Ann Stark

    2016-01-01

    Full Text Available Health profession students may need help establishing and maintaining positive health behaviors when they are in college. This study explored the effectiveness of text messaging as an innovative method for promoting an increase in daily physical activity. A convenience sample (N = 134 was recruited from students at a college of Health and Human Services in Michigan. The participants were randomized into an intervention or control group (n = 67 each. The intervention group received daily affective text messages encouraging more physical activity by taking more steps. The control group received only messages reminding them to report their number of steps. All of the participants received a pedometer, completed a demographics and daily habits questionnaire, and completed the Perceived Stress Scale (PSS. There was no significant difference between the intervention and control groups in their number of daily steps. However, the most inactive participants had a significant increase in steps during the study period. Health profession students’ lifestyle behaviors have consequences, as they become caregivers in our dynamic, demanding health-care system. For those with the greatest need for physical activity, encouraging such activity via text messaging may improve their ability to care for themselves and their clients.

  19. Systematic review of recess interventions to increase physical activity.

    Science.gov (United States)

    Ickes, Melinda J; Erwin, Heather; Beighle, Aaron

    2013-08-01

    With the rapid increase in obesity rates among youth, efforts to increase physical activity (PA) have become a priority. School-based strategies for PA promotion must be cost-effective, unobtrusive, and linked to improved academic performance. Efforts to maximize recess PA are advocated because of both health and academic benefits. The purpose of this manuscript was to review recess interventions aimed to improve PA among youth, and make recommendations to develop related best practices. An extensive literature search was conducted to include all primary research articles evaluating any recess intervention with PA as an outcome. The included 13 interventions represented both settings within the U.S and internationally, among preschools and elementary/primary schools. A variety of strategies were used within the design and implementation of each of the interventions including: added equipment/materials, markings, zones, teacher involvement, active video games, activity of the week, and activity cards. Of the included studies, 95% demonstrated positive outcomes as a result of the recess intervention. A number of simple, low-cost strategies can be implemented to maximize the amount of recess time students are allotted. Long-term follow-up studies are warranted for each of the recess strategies identified to be effective.

  20. Interactions Increase Forager Availability and Activity in Harvester Ants.

    Directory of Open Access Journals (Sweden)

    Evlyn Pless

    Full Text Available Social insect colonies use interactions among workers to regulate collective behavior. Harvester ant foragers interact in a chamber just inside the nest entrance, here called the 'entrance chamber'. Previous studies of the activation of foragers in red harvester ants show that an outgoing forager inside the nest experiences an increase in brief antennal contacts before it leaves the nest to forage. Here we compare the interaction rate experienced by foragers that left the nest and ants that did not. We found that ants in the entrance chamber that leave the nest to forage experienced more interactions than ants that descend to the deeper nest without foraging. Additionally, we found that the availability of foragers in the entrance chamber is associated with the rate of forager return. An increase in the rate of forager return leads to an increase in the rate at which ants descend to the deeper nest, which then stimulates more ants to ascend into the entrance chamber. Thus a higher rate of forager return leads to more available foragers in the entrance chamber. The highest density of interactions occurs near the nest entrance and the entrances of the tunnels from the entrance chamber to the deeper nest. Local interactions with returning foragers regulate both the activation of waiting foragers and the number of foragers available to be activated.

  1. Altered spontaneous brain activity in adolescent boys with pure conduct disorder revealed by regional homogeneity analysis.

    Science.gov (United States)

    Wu, Qiong; Zhang, Xiaocui; Dong, Daifeng; Wang, Xiang; Yao, Shuqiao

    2017-07-01

    Functional magnetic resonance imaging (fMRI) studies have revealed abnormal neural activity in several brain regions of adolescents with conduct disorder (CD) performing various tasks. However, little is known about the spontaneous neural activity in people with CD in a resting state. The aims of this study were to investigate CD-associated regional activity abnormalities and to explore the relationship between behavioral impulsivity and regional activity abnormalities. Resting-state fMRI (rs-fMRI) scans were administered to 28 adolescents with CD and 28 age-, gender-, and IQ-matched healthy controls (HCs). The rs-fMRI data were subjected to regional homogeneity (ReHo) analysis. ReHo can demonstrate the temporal synchrony of regional blood oxygen level-dependent signals and reflect the coordination of local neuronal activity facilitating similar goals or representations. Compared to HCs, the CD group showed increased ReHo bilaterally in the insula as well as decreased ReHo in the right inferior parietal lobule, right middle temporal gyrus and right fusiform gyrus, left anterior cerebellum anterior, and right posterior cerebellum. In the CD group, mean ReHo values in the left and the right insula correlated positively with Barratt Impulsivity Scale (BIS) total scores. The results suggest that CD is associated with abnormal intrinsic brain activity, mainly in the cerebellum and temporal-parietal-limbic cortices, regions that are related to emotional and cognitive processing. BIS scores in adolescents with CD may reflect severity of abnormal neuronal synchronization in the insula.

  2. Serotonin increases synaptic activity in olfactory bulb glomeruli.

    Science.gov (United States)

    Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

    2016-03-01

    Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. Copyright © 2016 the American Physiological Society.

  3. Nest predation increases with parental activity: separating nest site and parental activity effects.

    OpenAIRE

    Martin, T E; Scott, J; Menge, C

    2000-01-01

    Alexander Skutch hypothesized that increased parental activity can increase the risk of nest predation. We tested this hypothesis using ten open-nesting bird species in Arizona, USA. Parental activity was greater during the nestling than incubation stage because parents visited the nest frequently to feed their young during the nestling stage. However, nest predation did not generally increase with parental activity between nesting stages across the ten study species. Previous investigators h...

  4. Increasing physical activity with mobile devices: a meta-analysis.

    Science.gov (United States)

    Fanning, Jason; Mullen, Sean P; McAuley, Edward

    2012-11-21

    Regular physical activity has established physical and mental health benefits; however, merely one quarter of the U.S. adult population meets national physical activity recommendations. In an effort to engage individuals who do not meet these guidelines, researchers have utilized popular emerging technologies, including mobile devices (ie, personal digital assistants [PDAs], mobile phones). This study is the first to synthesize current research focused on the use of mobile devices for increasing physical activity. To conduct a meta-analysis of research utilizing mobile devices to influence physical activity behavior. The aims of this review were to: (1) examine the efficacy of mobile devices in the physical activity setting, (2) explore and discuss implementation of device features across studies, and (3) make recommendations for future intervention development. We searched electronic databases (PubMed, PsychINFO, SCOPUS) and identified publications through reference lists and requests to experts in the field of mobile health. Studies were included that provided original data and aimed to influence physical activity through dissemination or collection of intervention materials with a mobile device. Data were extracted to calculate effect sizes for individual studies, as were study descriptives. A random effects meta-analysis was conducted using the Comprehensive Meta-Analysis software suite. Study quality was assessed using the quality of execution portion of the Guide to Community Preventative Services data extraction form. Four studies were of "good" quality and seven of "fair" quality. In total, 1351 individuals participated in 11 unique studies from which 18 effects were extracted and synthesized, yielding an overall weight mean effect size of g = 0.54 (95% CI = 0.17 to 0.91, P = .01). Research utilizing mobile devices is gaining in popularity, and this study suggests that this platform is an effective means for influencing physical activity behavior. Our focus

  5. Playing active video games increases energy expenditure in children.

    Science.gov (United States)

    Graf, Diana L; Pratt, Lauren V; Hester, Casey N; Short, Kevin R

    2009-08-01

    To compare energy expenditure rates in children playing the physically active video games, Dance Dance Revolution (DDR) and Nintendo's Wii Sports in relation to treadmill walking. Energy expenditure, heart rate, step rate, and perceived exertion were measured in 14 boys and 9 girls (ages 10-13 years; BMI at 3-98th percentile for age and gender) while watching television at rest, playing DDR at 2 skill levels, playing Wii bowling and boxing, and walking at 2.6, 4.2, and 5.7 km/h. Arterial elasticity was measured at rest and immediately after gaming. Compared with watching television, energy expenditure while gaming or walking increased 2- to 3-fold. Similarly, high rates of energy expenditure, heart rate, and perceived exertion were elicited from playing Wii boxing, DDR level 2, or walking at 5.7 km/h. This occurred despite variations in step rate among activities, reflecting greater use of upper body during Wii play (lowest step rate) than during walking (highest step rate) or DDR play. Wii bowling and beginner level DDR elicited a 2-fold increase in energy expenditure compared to television watching. Large-artery elasticity declined immediately after both DDR and Wii. The change was inversely related to the increment in energy expenditure above rest achieved during the activity. Energy expenditure during active video game play is comparable to moderate-intensity walking. Thus, for children who spend considerable time playing electronic screen games for entertainment, physically active games seem to be a safe, fun, and valuable means of promoting energy expenditure.

  6. Live imaging of cysteine-cathepsin activity reveals dynamics of focal inflammation, angiogenesis, and polyp growth.

    Directory of Open Access Journals (Sweden)

    Elias Gounaris

    2008-08-01

    Full Text Available It has been estimated that up to 30% of detectable polyps in patients regress spontaneously. One major challenge in the evaluation of effective therapy of cancer is the readout for tumor regression and favorable biological response to therapy. Inducible near infra-red (NIR fluorescent probes were utilized to visualize intestinal polyps of mice hemizygous for a novel truncation of the Adenomatous Polyposis coli (APC gene. Laser Scanning Confocal Microscopy in live mice allowed visualization of cathepsin activity in richly vascularized benign dysplastic lesions. Using biotinylated suicide inhibitors we quantified increased activities of the Cathepsin B & Z in the polyps. More than (3/4 of the probe signal was localized in CD11b(+Gr1(+ myeloid derived suppressor cells (MDSC and CD11b(+F4/80(+ macrophages infiltrating the lesions. Polyposis was attenuated through genetic ablation of cathepsin B, and suppressed by neutralization of TNFalpha in mice. In both cases, diminished probe signal was accounted for by loss of MDSC. Thus, in vivo NIR imaging of focal cathepsin activity reveals inflammatory reactions etiologically linked with cancer progression and is a suitable approach for monitoring response to therapy.

  7. Community Lenses Revealing the Role of Sociocultural Environment on Physical Activity

    Science.gov (United States)

    Belon, Ana Paula; Nieuwendyk, Laura M.; Vallianatos, Helen; Nykiforuk, Candace I. J.

    2016-01-01

    Purpose To identify perceptions of how sociocultural environment enabled and hindered physical activity (PA) participation. Design Community-based participatory research. Setting Two semirural and two urban communities located in Alberta, Canada. Participants Thirty-five people (74.3% females, 71.4% aged 25–64 years) across the four communities. Method PhotoVoice activities occurred over 3 months during the spring of 2009. Participants were asked to document perceived environmental attributes that might foster or inhibit PA in their community. Photographs and narratives were shared in one-on-one interviews. Line-by-line coding of the transcripts was independently conducted by two researchers using an inductive approach. Codes were arranged into themes and subthemes, which were then organized into the Analysis Grid for Environments Linked to Obesity (ANGELO) framework. Results Six main themes (accompanied by subthemes) emerged: sociocultural aesthetics, safety, social involvement, PA motivation, cultural ideas of recreation, and car culture. Representative quotes and photographs illustrate enablers and obstacles identified by participants. Conclusion This PhotoVoice study revealed how aspects of participants’ sociocultural environments shaped their decisions to be physically active. Providing more PA resources is only one step in the promotion of supportive environments. Strategies should also account for the beautification and maintenance of communities, increasing feelings of safety, enhancement of social support among community members, popularization of PA, and mitigating car culture, among others. PMID:25973966

  8. Community Lenses Revealing the Role of Sociocultural Environment on Physical Activity.

    Science.gov (United States)

    Belon, Ana Paula; Nieuwendyk, Laura M; Vallianatos, Helen; Nykiforuk, Candace I J

    2016-01-01

    To identify perceptions of how sociocultural environment enabled and hindered physical activity (PA) participation. Community-based participatory research. Two semirural and two urban communities located in Alberta, Canada. Thirty-five people (74.3% females, 71.4% aged 25-64 years) across the four communities. PhotoVoice activities occurred over 3 months during the spring of 2009. Participants were asked to document perceived environmental attributes that might foster or inhibit PA in their community. Photographs and narratives were shared in one-on-one interviews. Line-by-line coding of the transcripts was independently conducted by two researchers using an inductive approach. Codes were arranged into themes and subthemes, which were then organized into the Analysis Grid for Environments Linked to Obesity (ANGELO) framework. Six main themes (accompanied by subthemes) emerged: sociocultural aesthetics, safety, social involvement, PA motivation, cultural ideas of recreation, and car culture. Representative quotes and photographs illustrate enablers and obstacles identified by participants. This PhotoVoice study revealed how aspects of participants' sociocultural environments shaped their decisions to be physically active. Providing more PA resources is only one step in the promotion of supportive environments. Strategies should also account for the beautification and maintenance of communities, increasing feelings of safety, enhancement of social support among community members, popularization of PA, and mitigating car culture, among others.

  9. Attributing Increased River Flooding in the Future: Hydrodynamic Downscaling Reveals Role of Plant Physiological Responses to Increased CO2 is First Order

    Science.gov (United States)

    Fowler, M. D.; Kooperman, G. J.; Pritchard, M. S.; Randerson, J. T.

    2017-12-01

    River flooding events, which are the most frequently occurring natural disaster today, are expected to become more frequent and intense in response to climate change. However, the magnitude of these changes remains debated, in part due to uncertainty in our understanding of the physical processes that contribute to these events and their representation in global climate models. While the intensification of precipitation has been shown to be a primary driver of increased flooding, plant physiological responses to increasing CO2 may also play an important role. As the atmospheric concentration of CO2 increases, plants may respond by reducing the width of their stomata (i.e. stomatal conductance), which can decrease water lost through transpiration and in turn maintain higher soil moisture levels. On long timescales, reduced transpiration has been shown to increase average runoff, but on short timescales elevated soil moisture can also increase instantaneous runoff by limiting the rate at which water is able to infiltrate the soil surface. Here, through hydrodynamic downscaling, we isolate the portion of flooding amplification that can be attributed to the physiological response to increasing CO2. This builds on a new analysis that has revealed such physiological effects can rival changes caused by the atmospheric response alone in the tails of the runoff distribution. We use a set of four simulations run with the Community Earth System Model: one pre-industrial control simulation and three others that are forced with four times CO2. In the three climate change simulations, the increased CO2 is applied only to the land-surface, only to the atmosphere, and to both, respectively. Thirty years of daily runoff from these experiments are used as input for the hydrodynamic CaMa-Flood model. Our results reveal that both the radiative and physiological responses to climate change contribute significantly to future changes in flood return period and inundated area. This

  10. Increased dopaminergic activity in socially isolated rats: an electrophysiological study

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Helboe, Lone; Fink-Jensen, Anders

    2010-01-01

    The development of animal models mimicking symptoms associated with schizophrenia has been a critical step in understanding the neurobiological mechanisms underlying the disease. Long-term social isolation from weaning in rodents, a model based on the neurodevelopmental hypothesis of schizophrenia......, has been suggested to mimic some of the deficits seen in schizophrenic patients. We confirm in the present study that socially isolated rats display an increase in both spontaneous and d-amphetamine-induced locomotor activity, as well as deficits in sensorimotor gating as assessed in a pre......, and a change of firing activity towards a more irregular and bursting firing pattern. Taken together, our findings suggest that the behavioral phenotype induced by social isolation may be driven by an overactive dopamine system....

  11. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    Directory of Open Access Journals (Sweden)

    Ari J S Ferreira

    Full Text Available Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  12. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    KAUST Repository

    Ferreira, Ari J S

    2014-06-12

    Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world\\'s oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  13. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    KAUST Repository

    Ferreira, Ari J S; Siam, Rania; Setubal, Joã o C; Moustafa, Ahmed; Sayed, Ahmed; Chambergo, Felipe S; Dawe, Adam S; Ghazy, Mohamed A; Sharaf, Hazem; Ouf, Amged; Alam, Intikhab; Abdel-Haleem, Alyaa M; Lehvä slaiho, Heikki; Ramadan, Eman; Antunes, André ; Stingl, Ulrich; Archer, John A.C.; Jankovic, Boris R; Sogin, Mitchell; Bajic, Vladimir B.; El-Dorry, Hamza

    2014-01-01

    Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  14. Both novelty and expertise increase action observation network activity

    Directory of Open Access Journals (Sweden)

    Sook-Lei eLiew

    2013-09-01

    Full Text Available Our experiences with others affect how we perceive their actions. In particular, activity in bilateral premotor and parietal cortices during action observation, collectively known as the action observation network (AON, is modulated by one’s expertise with the observed actions or individuals. However, conflicting reports suggest that AON activity is greatest both for familiar and unfamiliar actions. The current study examines the effects of different types and amounts of experience (e.g., visual, interpersonal, personal on AON activation. fMRI was used to scan 16 healthy participants without prior experience with individuals with amputations (novices, 11 experienced occupational therapists (OTs who had varying amounts of experience with individuals with amputations, and one individual born with below-elbow residual limbs (participant CJ, as they viewed video clips of goal-matched actions performed by an individual with residual limbs and by an individual with hands. Participants were given increased visual exposure to actions performed by both effectors midway through the scanning procedure. Novices demonstrated a large AON response to the initial viewing of an individual with residual limbs compared to one with hands, but this signal was attenuated after they received visual exposure to both effectors. In contrast, OTs, who had moderate familiarity with residual limbs, demonstrated a lower AON response upon initial viewing—similar to novices after they received visual exposure. At the other extreme, CJ, who has extreme familiarity with residual limbs both visually and motorically, shows a largely increased left-lateralized AON response, exceeding that of novices and experienced OTs, when viewing the residual limb compared to hand actions. These results suggest that a nuanced model of AON engagement is needed to explain how cases of both extreme experience (CJ and extreme novelty (novices can result in the greatest AON activity.

  15. Revealing School Counselors' Perspectives on Using Physical Activity and Consulting with Coaches

    Science.gov (United States)

    Hayden, Laura; Silva, Meghan Ray; Gould, Kaitlin

    2018-01-01

    This study reveals school counselors' perspectives on using physical activity and a consultative process with coaches to provide school-based support for youth. Emerging from this exploration are ways that school-based physical activity might be used to help students develop life skills and to remove barriers to systemic integration of…

  16. Transient extracellular application of gold nanostars increases hippocampal neuronal activity.

    Science.gov (United States)

    Salinas, Kirstie; Kereselidze, Zurab; DeLuna, Frank; Peralta, Xomalin G; Santamaria, Fidel

    2014-08-20

    With the increased use of nanoparticles in biomedical applications there is a growing need to understand the effects that nanoparticles may have on cell function. Identifying these effects and understanding the mechanism through which nanoparticles interfere with the normal functioning of a cell is necessary for any therapeutic or diagnostic application. The aim of this study is to evaluate if gold nanoparticles can affect the normal function of neurons, namely their activity and coding properties. We synthesized star shaped gold nanoparticles of 180 nm average size. We applied the nanoparticles to acute mouse hippocampal slices while recording the action potentials from single neurons in the CA3 region. Our results show that CA3 hippocampal neurons increase their firing rate by 17% after the application of gold nanostars. The increase in excitability lasted for as much as 50 minutes after a transient 5 min application of the nanoparticles. Further analyses of the action potential shape and computational modeling suggest that nanoparticles block potassium channels responsible for the repolarization of the action potentials, thus allowing the cell to increase its firing rate. Our results show that gold nanoparticles can affect the coding properties of neurons by modifying their excitability.

  17. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

  18. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    Science.gov (United States)

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  19. Activation of the zymogen to urokinase-type plasminogen activator is associated with increased interdomain flexibility

    DEFF Research Database (Denmark)

    Behrens, Manja A; Bøtkjær, Kenneth Alrø; Goswami, Sumit

    2011-01-01

    A key regulatory step for serine proteases of the trypsin clan is activation of the initially secreted zymogens, leading to an increase in activity by orders of magnitude. Zymogen activation occurs by cleavage of a single peptide bond near the N-terminus of the catalytic domain. Besides the catal...

  20. Use of active video games to increase physical activity in children: a (virtual) reality?

    Science.gov (United States)

    Foley, Louise; Maddison, Ralph

    2010-02-01

    There has been increased research interest in the use of active video games (in which players physically interact with images onscreen) as a means to promote physical activity in children. The aim of this review was to assess active video games as a means of increasing energy expenditure and physical activity behavior in children. Studies were obtained from computerized searches of multiple electronic bibliographic databases. The last search was conducted in December 2008. Eleven studies focused on the quantification of the energy cost associated with playing active video games, and eight studies focused on the utility of active video games as an intervention to increase physical activity in children. Compared with traditional nonactive video games, active video games elicited greater energy expenditure, which was similar in intensity to mild to moderate intensity physical activity. The intervention studies indicate that active video games may have the potential to increase free-living physical activity and improve body composition in children; however, methodological limitations prevent definitive conclusions. Future research should focus on larger, methodologically sound intervention trials to provide definitive answers as to whether this technology is effective in promoting long-term physical activity in children.

  1. INCREASED TISSUE TRANSGLUTAMINASE LEVELS ARE ASSOCIATED WITH INCREASED EPILEPTIFORM ACTIVITY IN ELECTROENCEPHALOGRAPHY AMONG PATIENTS WITH CELIAC DISEASE

    Directory of Open Access Journals (Sweden)

    Sedat IŞIKAY

    2015-12-01

    Full Text Available Background - Celiac disease is an autoimmune systemic disorder in genetically predisposed individuals precipitated by gluten ingestion. Objective - In this study, we aimed to determine asymptomatic spike-and-wave findings on electroencephalography in children with celiac disease. Methods - A total of 175 children with the diagnosis of celiac disease (study group and 99 age- and sex-matched healthy children as controls (control group were included in the study. In order to determine the effects of gluten free diet on laboratory and electroencephalography findings, the celiac group is further subdivided into two as newly-diagnosed and formerly-diagnosed patients. Medical histories of all children and laboratory findings were all recorded and neurologic statuses were evaluated. All patients underwent a sleep and awake electroencephalography. Results - Among 175 celiac disease patients included in the study, 43 were newly diagnosed while 132 were formerly-diagnosed patients. In electroencephalography evaluation of patients the epileptiform activity was determined in 4 (9.3% of newly diagnosed and in 2 (1.5% of formerly diagnosed patients; on the other hand the epileptiform activity was present in only 1 (1.0% of control cases. There was a statistically significant difference between groups in regards to the presence of epileptiform activity in electroencephalography. Pearson correlation analysis revealed that epileptiform activity in both sleep and awake electroencephalography were positively correlated with tissue transglutaminase levels (P=0.014 and P=0.019, respectively. Conclusion - We have determined an increased epileptiform activity frequency among newly-diagnosed celiac disease patients compared with formerly-diagnosed celiac disease patients and control cases. Moreover the tissue transglutaminase levels were also correlated with the presence of epileptiform activity in electroencephalography. Among newly diagnosed celiac disease patients

  2. HYPNOBIRTHING INCREASE PAIN TOLERANCE AND ANXIETY IN ACTIVE PHASE LABOR

    Directory of Open Access Journals (Sweden)

    Nursalam Nursalam

    2017-07-01

    Full Text Available Introduction: The main problem of inpartu mother was a labour pain and anxiety. The etiology of labour pain has been determained by dilatation and cervic’s tickness. The objective of this study was to examine the effect of hypnobirthing relaxation on the pain tolerance and anxiety responses in labor. Method: A pre experimental static group comparison purposive sampling design was used in this study. Population were all pregnant women in age of pregnancies between 38 until 39 weeks at RSUD Wangaya Denpasar. There were 12 respondents who met to the inclusion criteria divided into 6 respondents were given hypnobirthing relaxation intervention and 6 respondents as the control group. The independent variable was hypnobirthing relaxation and dependent variables were tolerance of pain and anxiety responses. Data were collected by using observation and questionnaire, then data were analyzed by using Mann Whitney U Test with significance level p=0.05. Result: The result showed that hypnobirthing relaxation had an effect on the pain tolerance and anxiety responses (p=0.015. Discussion: It can be concluded that the hypnobirthing relaxation has an effect to increase the pain tolerance and to decrease anxiety responses in active phase of labour. It is recommended to the hospital that have an ante natal care to hypnobirthing relaxation technique. Further studies should measure the effect of hynobirthing relaxation on increasing of β-endorfin in active phase labour.

  3. Hypocapnia induces caspase-3 activation and increases Abeta production.

    Science.gov (United States)

    Xie, Zhongcong; Moir, Robert D; Romano, Donna M; Tesco, Giuseppina; Kovacs, Dora M; Tanzi, Rudolph E

    2004-01-01

    At least half of all cases of early onset (<60) familial Alzheimer's disease (FAD) are caused by any of over 150 mutations in three genes: the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2). Mutant forms of PS1 have been shown to sensitize cells to apoptotic cell death. We investigated the effects of hypocapnia, a risk factor for both cognitive and neurodevelopment deficits, on caspase-3 activation, apoptosis, and amyloid beta-protein (Abeta) production, and assessed the influence of the PS1Delta9 FAD mutation on these effects. For this purpose, we exposed stably transfected H4 human neuroglioma cells to conditions consistent with hypocapnia (PCO2<40 mm Hg) and hypocapnia plus hypoxia (PO2<21%). Hypocapnia (20 mm Hg CO2 for 6 h) induced caspase-3 activation and apoptosis; the PS1Delta9 FAD mutation significantly potentiated these effects. Moreover, the combination of hypocapnia (20 mm Hg CO2) and hypoxia (5%O2) induced caspase-3 activation and apoptosis in a synergistic manner. Hypocapnia (5 and 20 mm Hg CO2 for 6 h) also led to an increased Abeta production. The findings suggest that hypocapnia (e.g. during general anesthesia) could exacerbate AD neuropathogenesis. Copyright (c) 2004 S. Karger AG, Basel.

  4. Municipal services as a means of increasing the citizens’ activity

    Directory of Open Access Journals (Sweden)

    Olga Valeryevna Yakhina

    2015-06-01

    Full Text Available Objective to propose ways of increasing the activity of Russian citizens through the institution of municipal services. Methods the methodological basis of the study was a systematic and integrated approach to the analysis of the institution of municipal services. The general philosophical method was used as well as general scientific methods of cognition dialectical systemic analysis and synthesis induction and deduction and specific scientific methods comparativelegal formallegal historicallegal sociological systemicfunctional theoreticalprognostic linguolegal methods. In particular the formallegal method was used to study the problem of the legal fixation of administrative regulations statuses the theoreticalprognostic method was used in preparing recommendations to increase the activity of citizens. Results the municipal services are regarded by the author as a way to meet the needs of the population of a particular territory and as a way of interaction between local public authorities and the citizens. The issue of the functioning of emunicipalities is studied as well as the shortcomings in the legal regulation in this field. The problem is discussed of insufficient use of the Internet in the local authoritiesrsquo interaction with citizens. The author suggests ways to improve the Federal Law quotOn the organization of state and municipal servicesquot N 210FZ of July 2 2010 regarding the use of the Internet as a means of feedback between the public authorities and the population of a territory. Special attention is paid to normative legal acts regulating the procedure of municipal services provision i.e. the administrative regulations of local authorities. The emerging challenges in the legal regulation of the specified institution are identified the solutions to the identified problems are proposed. Scientific novelty in 2010 the institution of municipal services has undergone significant modernization thus the necessity to its research

  5. Increasing evidence that bats actively forage at wind turbines.

    Science.gov (United States)

    Foo, Cecily F; Bennett, Victoria J; Hale, Amanda M; Korstian, Jennifer M; Schildt, Alison J; Williams, Dean A

    2017-01-01

    Although the ultimate causes of high bat fatalities at wind farms are not well understood, several lines of evidence suggest that bats are attracted to wind turbines. One hypothesis is that bats would be attracted to turbines as a foraging resource if the insects that bats prey upon are commonly present on and around the turbine towers. To investigate the role that foraging activity may play in bat fatalities, we conducted a series of surveys at a wind farm in the southern Great Plains of the US from 2011-2016. From acoustic monitoring we recorded foraging activity, including feeding buzzes indicative of prey capture, in the immediate vicinity of turbine towers from all six bat species known to be present at this site. From insect surveys we found Lepidoptera, Coleoptera, and Orthoptera in consistently high proportions over several years suggesting that food resources for bats were consistently available at wind turbines. We used DNA barcoding techniques to assess bat diet composition of (1) stomach contents from 47 eastern red bat ( Lasiurus borealis ) and 24 hoary bat ( Lasiurus cinereus ) carcasses collected in fatality searches, and (2) fecal pellets from 23 eastern red bats that were found on turbine towers, transformers, and tower doors. We found that the majority of the eastern red bat and hoary bat stomachs, the two bat species most commonly found in fatality searches at this site, were full or partially full, indicating that the bats were likely killed while foraging. Although Lepidoptera and Orthoptera dominated the diets of these two bat species, both consumed a range of prey items with individual bats having from one to six insect species in their stomachs at the time of death. The prey items identified from eastern red bat fecal pellets showed similar results. A comparison of the turbine insect community to the diet analysis results revealed that the most abundant insects at wind turbines, including terrestrial insects such as crickets and several

  6. Charcoal Increases Microbial Activity in Eastern Sierra Nevada Forest Soils

    Directory of Open Access Journals (Sweden)

    Zachary W. Carter

    2018-02-01

    Full Text Available Fire is an important component of forests in the western United States. Not only are forests subjected to wildfires, but fire is also an important management tool to reduce fuels loads. Charcoal, a product of fire, can have major impacts on carbon (C and nitrogen (N cycling in forest soils, but it is unclear how these effects vary by dominant vegetation. In this study, soils collected from Jeffrey pine (JP or lodgepole pine (LP dominated areas and amended with charcoal derived from JP or LP were incubated to assess the importance of charcoal on microbial respiration and potential nitrification. In addition, polyphenol sorption was measured in unamended and charcoal-amended soils. In general, microbial respiration was highest at the 1% and 2.5% charcoal additions, but charcoal amendment had limited effects on potential nitrification rates throughout the incubation. Microbial respiration rates decreased but potential nitrification rates increased over time across most treatments. Increased microbial respiration may have been caused by priming of native organic matter rather than the decomposition of charcoal itself. Charcoal had a larger stimulatory effect on microbial respiration in LP soils than JP soils. Charcoal type had little effect on microbial processes, but polyphenol sorption was higher on LP-derived than JP-derived charcoal at higher amendment levels despite surface area being similar for both charcoal types. The results from our study suggest that the presence of charcoal can increase microbial activity in soils, but the exact mechanisms are still unclear.

  7. Natural high pCO2 increases autotrophy in Anemonia viridis (Anthozoa) as revealed from stable isotope (C, N) analysis.

    Science.gov (United States)

    Horwitz, Rael; Borell, Esther M; Yam, Ruth; Shemesh, Aldo; Fine, Maoz

    2015-03-05

    Contemporary cnidarian-algae symbioses are challenged by increasing CO2 concentrations (ocean warming and acidification) affecting organisms' biological performance. We examined the natural variability of carbon and nitrogen isotopes in the symbiotic sea anemone Anemonia viridis to investigate dietary shifts (autotrophy/heterotrophy) along a natural pCO2 gradient at the island of Vulcano, Italy. δ(13)C values for both algal symbionts (Symbiodinium) and host tissue of A. viridis became significantly lighter with increasing seawater pCO2. Together with a decrease in the difference between δ(13)C values of both fractions at the higher pCO2 sites, these results indicate there is a greater net autotrophic input to the A. viridis carbon budget under high pCO2 conditions. δ(15)N values and C/N ratios did not change in Symbiodinium and host tissue along the pCO2 gradient. Additional physiological parameters revealed anemone protein and Symbiodinium chlorophyll a remained unaltered among sites. Symbiodinium density was similar among sites yet their mitotic index increased in anemones under elevated pCO2. Overall, our findings show that A. viridis is characterized by a higher autotrophic/heterotrophic ratio as pCO2 increases. The unique trophic flexibility of this species may give it a competitive advantage and enable its potential acclimation and ecological success in the future under increased ocean acidification.

  8. Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients.

    Directory of Open Access Journals (Sweden)

    Fabrice Armougom

    Full Text Available BACKGROUND: Studies of the bacterial communities of the gut microbiota have revealed a shift in the ratio of Firmicutes and Bacteroidetes in obese patients. Determining the variations of microbial communities in feces may be beneficial for the identification of specific profiles in patients with abnormal weights. The roles of the archaeon Methanobrevibacter smithii and Lactobacillus species have not been described in these studies. METHODS AND FINDINGS: We developed an efficient and robust real-time PCR tool that includes a plasmid-based internal control and allows for quantification of the bacterial divisions Bacteroidetes, Firmicutes, and Lactobacillus as well as the methanogen M. smithii. We applied this technique to the feces of 20 obese subjects, 9 patients with anorexia nervosa, and 20 normal-weight healthy controls. Our results confirmed a reduction in the Bacteroidetes community in obese patients (p<0.01. We found a significantly higher Lactobacillus species concentration in obese patients than in lean controls (p=0.0197 or anorexic patients (p=0.0332. The M. smithii concentration was much higher in anorexic patients than in the lean population (p=0.0171. CONCLUSIONS: Lactobacillus species are widely used as growth promoters in the farm industry and are now linked to obesity in humans. The study of the bacterial flora in anorexic patients revealed an increase in M. smithii. This increase might represent an adaptive use of nutrients in this population.

  9. Engagement in activities revealing the body and psychosocial adjustment in adults with a trans-tibial prosthesis.

    Science.gov (United States)

    Donovan-Hall, M K; Yardley, L; Watts, R J

    2002-04-01

    The purpose of this study was to examine the effects of the appearance of a prosthesis on social behaviour, social discomfort and psychological well-being in eleven amputees taking delivery of a prosthesis with a silicone cover. Two new scales were developed: the 'Engagement in everyday activities involving revealing the body' (EEARB); and the 'Discomfort-Engagement in everyday activities involving revealing the body' (Discomfort-EEARB) scales. The psychometric properties of these scales were determined using a sample of 101 able-bodied adults. The Hospital Anxiety and Depression Scale and the Rosenberg Self-Esteem Scale were also used to measure psychological well-being in the amputee sample. The EEARB and Discomfort-EEARB proved to have good reliability and validity. Comparison of amputees' scores prior to receiving the silicone cosmesis with those of the able-bodied adults revealed significant behavioural limitations and social discomfort, associated with low self-esteem, anxiety and depression. There was a significant increase in amputees' scores three months afier taking delivery of their prosthesis, indicating that amputees reported engaging in more activities which involved revealing their body, and that they would feel more comfortable in situations which involved revealing the body. As the amputee sample available was small and self-selected, it is not possible to generalise these findings to the amputee population as a whole. However, since there is little previous research investigating the effects of the appearance of the prosthesis, these findings demonstrate the need for further research in this area.

  10. Increases in Use and Activity Due to Urban Renewal

    DEFF Research Database (Denmark)

    Andersen, Henriette Bondo; Christiansen, Lars Breum; Klinker, Charlotte Demant

    2017-01-01

    Introduction Urban green space and other recreational facilities are associated with physical activity. For adolescents living in multistory housing, public outdoor spaces that support physical activity may play an important role in activity promotion strategies. However, stronger evidence for a ...

  11. Increased 5α-reductase activity in idiopathic hirsutism

    International Nuclear Information System (INIS)

    Serafini, P.; Lobo, R.A.

    1985-01-01

    In vitro, genital skin 5α-reductase activity (5α-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5α-RA. In vitro 5α-RA was assessed by incubations of skin with 14 C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5α-androstane 3α-17β-estradiol (3α-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3α-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3α-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5α-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5α-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5α-RA

  12. A Global Genomic Screening Strategy Reveals Diverse Activators of Constitutive Activated Receptor (CAR)

    Science.gov (United States)

    A comprehensive survey of conditions that activate CAR in the mouse liver has not been carried out but would be useful in understanding their impact on CAR-dependent liver tumor induction. A gene signature dependent on CAR activation was identified by comparing the transcript pr...

  13. Dual gene activation and knockout screen reveals directional dependencies in genetic networks. | Office of Cancer Genomics

    Science.gov (United States)

    Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair.

  14. Transcriptional decomposition reveals active chromatin architectures and cell specific regulatory interactions

    DEFF Research Database (Denmark)

    Rennie, Sarah; Dalby, Maria; van Duin, Lucas

    2018-01-01

    Transcriptional regulation is tightly coupled with chromosomal positioning and three-dimensional chromatin architecture. However, it is unclear what proportion of transcriptional activity is reflecting such organisation, how much can be informed by RNA expression alone and how this impacts disease...... proportion of total levels and is highly informative of topological associating domain activities and organisation, revealing boundaries and chromatin compartments. Furthermore, expression data alone accurately predict individual enhancer-promoter interactions, drawing features from expression strength...... between transcription and chromatin architecture....

  15. Increased 5. cap alpha. -reductase activity in idiopathic hirsutism

    Energy Technology Data Exchange (ETDEWEB)

    Serafini, P.; Lobo, R.A.

    1985-01-01

    In vitro, genital skin 5..cap alpha..-reductase activity (5..cap alpha..-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5..cap alpha..-RA. In vitro 5..cap alpha..-RA was assessed by incubations of skin with /sup 14/C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5..cap alpha..-androstane 3..cap alpha..-17..beta..-estradiol (3..cap alpha..-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3..cap alpha..-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3..cap alpha..-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5..cap alpha..-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5..cap alpha..-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5..cap alpha..-RA.

  16. Electron Tomography Reveals the Active Phase–Support Interaction in Sulfidic Hydroprocessing Catalysts

    NARCIS (Netherlands)

    Eijsbouts, Sonja; Li, Xuang; Juan-Alcaniz, Jana; van den Oetelaar, Leon C A; Bergwerff, Jaap; Loos, Joachim; Carlsson, Anna; Vogt, E.T.C.

    2017-01-01

    Conventional two-dimensional (2D) transmission electron microscopy of sulfidic hydroprocessing catalysts can be deceiving and give the impression that parts of the support are overloaded with active phase. High-angle annular dark field scanning transmission electron microscopy tomography reveals

  17. Altered behavior in spotted hyenas associated with increased human activity

    Science.gov (United States)

    Boydston, Erin E.; Kapheim, Karen M.; Watts, Heather E.; Szykman, Micaela; Holekamp, Kay E.

    2003-01-01

    To investigate how anthropogenic activity might affect large carnivores, we studied the behaviour of spotted hyenas (Crocuta crocuta) during two time periods. From 1996 to 1998, we documented the ecological correlates of space utilization patterns exhibited by adult female hyenas defending a territory at the edge of a wildlife reserve in Kenya. Hyenas preferred areas near dense vegetation but appeared to avoid areas containing the greatest abundance of prey, perhaps because these were also the areas of most intensive livestock grazing. We then compared hyena behaviour observed in 1996–98 with that observed several years earlier and found many differences. Female hyenas in 1996–98 were found farther from dens, but closer to dense vegetation and to the edges of their territory, than in 1988–90. Recent females also had larger home ranges, travelled farther between consecutive sightings, and were more nocturnal than in 1988–90. Finally, hyenas occurred in smaller groups in 1996–98 than in 1988–90. We also found several changes in hyena demography between periods. We next attempted to explain differences observed between time periods by testing predictions of hypotheses invoking prey abundance, climate, interactions with lions, tourism and livestock grazing. Our data were consistent with the hypothesis that increased reliance on the reserve for livestock grazing was responsible for observed changes. That behavioural changes were not associated with decreased hyena population density suggests the behavioural plasticity typical of this species may protect it from extinction.

  18. Resveratrol Reactivates Latent HIV through Increasing Histone Acetylation and Activating Heat Shock Factor 1.

    Science.gov (United States)

    Zeng, Xiaoyun; Pan, Xiaoyan; Xu, Xinfeng; Lin, Jian; Que, Fuchang; Tian, Yuanxin; Li, Lin; Liu, Shuwen

    2017-06-07

    The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression, although its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Mode of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homologue 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC). However, latent HIV was reactivated by resveratrol mediated through increasing histone acetylation and activation of heat shock factor 1 (HSF1). Additionally, synergistic activation of the latent HIV reservoirs was observed under cotreatment with resveratrol and conventional LRAs. Collectively, this research reveals that resveratrol is a natural LRA and shows promise for HIV therapy.

  19. Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum.

    Science.gov (United States)

    Kenyon, Amy; Gavriouchkina, Daria; Zorman, Jernej; Napolitani, Giorgio; Cerundolo, Vincenzo; Sauka-Spengler, Tatjana

    2017-07-26

    The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1β, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1β transcription.

  20. Trapezius muscle activity increases during near work activity regardless of accommodation/vergence demand level.

    Science.gov (United States)

    Richter, H O; Zetterberg, C; Forsman, M

    2015-07-01

    To investigate if trapezius muscle activity increases over time during visually demanding near work. The vision task consisted of sustained focusing on a contrast-varying black and white Gabor grating. Sixty-six participants with a median age of 38 (range 19-47) fixated the grating from a distance of 65 cm (1.5 D) during four counterbalanced 7-min periods: binocularly through -3.5 D lenses, and monocularly through -3.5 D, 0 D and +3.5 D. Accommodation, heart rate variability and trapezius muscle activity were recorded in parallel. General estimating equation analyses showed that trapezius muscle activity increased significantly over time in all four lens conditions. A concurrent effect of accommodation response on trapezius muscle activity was observed with the minus lenses irrespective of whether incongruence between accommodation and convergence was present or not. Trapezius muscle activity increased significantly over time during the near work task. The increase in muscle activity over time may be caused by an increased need of mental effort and visual attention to maintain performance during the visual tasks to counteract mental fatigue.

  1. Processing of Building Binder Materials to Increase their Activation

    Science.gov (United States)

    Fediuk, R. S.; Garmashov, I. S.; Kuzmin, D. E.; Stoyushko, N. Yu; Gladkova, N. A.

    2018-01-01

    The paper deals modern physical methods of activation of building powder materials. During mechanical activation a composite binder active molecules cement minerals occur in the destruction of the molecular defects in the areas of packaging and breaking metastable phase decompensation intermolecular forces. The process is accompanied by a change in the kinetics of hardening of Portland cement. Activated concrete has a number of features that are used as design characteristics of structures and are due to the structure of the activated binder and its contacts with concrete aggregates. These features also have a significant impact on the nature of the destruction of concrete under load, changing the boundaries of its microcracks and durability.

  2. A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

    Science.gov (United States)

    Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

    2016-04-01

    Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

  3. Hydrophilic Phage-Mimicking Membrane Active Antimicrobials Reveal Nanostructure-Dependent Activity and Selectivity.

    Science.gov (United States)

    Jiang, Yunjiang; Zheng, Wan; Kuang, Liangju; Ma, Hairong; Liang, Hongjun

    2017-09-08

    The prevalent wisdom on developing membrane active antimicrobials (MAAs) is to seek a delicate, yet unquantified, cationic-hydrophobic balance. Inspired by phages that use nanostructured protein devices to invade bacteria efficiently and selectively, we study here the antibiotic role of nanostructures by designing spherical and rod-like polymer molecular brushes (PMBs) that mimic the two basic structural motifs of bacteriophages. Three model PMBs with different well-defined geometries consisting of multiple, identical copies of densely packed poly(4-vinyl-N-methylpyridine iodide) branches are synthesized by controlled/"living" polymerization, reminiscent of the viral structural motifs comprised of multiple copies of protein subunits. We show that, while the individual linear-chain polymer branch that makes up the PMBs is hydrophilic and a weak antimicrobial, amphiphilicity is not a required antibiotic trait once nanostructures come into play. The nanostructured PMBs induce an unusual topological transition of bacterial but not mammalian membranes to form pores. The sizes and shapes of the nanostructures further help define the antibiotic activity and selectivity of the PMBs against different families of bacteria. This study highlights the importance of nanostructures in the design of MAAs with high activity, low toxicity, and target specificity.

  4. Data on the effect of conductive hearing loss on auditory and visual cortex activity revealed by intrinsic signal imaging.

    Science.gov (United States)

    Teichert, Manuel; Bolz, Jürgen

    2017-10-01

    This data article provides additional data related to the research article entitled "Simultaneous intrinsic signal imaging of auditory and visual cortex reveals profound effects of acute hearing loss on visual processing" (Teichert and Bolz, 2017) [1]. The primary auditory and visual cortex (A1 and V1) of adult male C57BL/6J mice (P120-P240) were mapped simultaneously using intrinsic signal imaging (Kalatsky and Stryker, 2003) [2]. A1 and V1 activity evoked by combined auditory and visual stimulation were measured before and after conductive hearing loss (CHL) induced by bilateral malleus removal. We provide data showing that A1 responsiveness evoked by sounds of different sound pressure levels (SPL) decreased after CHL whereas visually evoked V1 activity increased after this intervention. In addition, we also provide imaging data on percentage of V1 activity increases after CHL compared to pre-CHL.

  5. Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Ytting, H; Jensenius, Jens Christian; Christensen, I J

    2004-01-01

    BACKGROUND: Postoperative bacterial infectious complications are frequent in patients with colorectal cancer (CRC), with subsequent increased recurrence rates and poor prognosis. Deficiency of the mannan-binding lectin (MBL) complement activation pathway may cause increased risk of infection......: Serum MBL concentrations and MBL/MASP activity were determined using immunofluorometric assays. The levels are presented as the median, inter-quartile range and range. RESULTS: Serum MBL levels were significantly (P cancer (1384 (400-2188) ng/mL) (median...... in the colon or rectum, and disease stages according to Dukes' classification. No statistical difference (P=0.20) in frequency of MBL deficiency was found between the patients (20%) and the donors (27%). CONCLUSIONS: Overall, the MBL complement activation pathway is significantly increased in patients...

  6. Correlation of neural activity with behavioral kinematics reveals distinct sensory encoding and evidence accumulation processes during active tactile sensing.

    Science.gov (United States)

    Delis, Ioannis; Dmochowski, Jacek P; Sajda, Paul; Wang, Qi

    2018-03-23

    Many real-world decisions rely on active sensing, a dynamic process for directing our sensors (e.g. eyes or fingers) across a stimulus to maximize information gain. Though ecologically pervasive, limited work has focused on identifying neural correlates of the active sensing process. In tactile perception, we often make decisions about an object/surface by actively exploring its shape/texture. Here we investigate the neural correlates of active tactile decision-making by simultaneously measuring electroencephalography (EEG) and finger kinematics while subjects interrogated a haptic surface to make perceptual judgments. Since sensorimotor behavior underlies decision formation in active sensing tasks, we hypothesized that the neural correlates of decision-related processes would be detectable by relating active sensing to neural activity. Novel brain-behavior correlation analysis revealed that three distinct EEG components, localizing to right-lateralized occipital cortex (LOC), middle frontal gyrus (MFG), and supplementary motor area (SMA), respectively, were coupled with active sensing as their activity significantly correlated with finger kinematics. To probe the functional role of these components, we fit their single-trial-couplings to decision-making performance using a hierarchical-drift-diffusion-model (HDDM), revealing that the LOC modulated the encoding of the tactile stimulus whereas the MFG predicted the rate of information integration towards a choice. Interestingly, the MFG disappeared from components uncovered from control subjects performing active sensing but not required to make perceptual decisions. By uncovering the neural correlates of distinct stimulus encoding and evidence accumulation processes, this study delineated, for the first time, the functional role of cortical areas in active tactile decision-making. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

    International Nuclear Information System (INIS)

    Teutschbein, Janka; Haydn, Johannes M; Samans, Birgit; Krause, Michael; Eilers, Martin; Schartl, Manfred; Meierjohann, Svenja

    2010-01-01

    Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation. Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration. Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development

  8. Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

    Directory of Open Access Journals (Sweden)

    Krause Michael

    2010-07-01

    Full Text Available Abstract Background Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation. Methods Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Results Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1, early growth response 1 (Egr1, osteopontin (Opn, insulin-like growth factor binding protein 3 (Igfbp3, dual-specificity phosphatase 4 (Dusp4, and tumor-associated antigen L6 (Taal6. Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration. Conclusion Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute

  9. Targeted massively parallel sequencing of angiosarcomas reveals frequent activation of the mitogen activated protein kinase pathway

    Science.gov (United States)

    Murali, Rajmohan; Chandramohan, Raghu; Möller, Inga; Scholz, Simone L.; Berger, Michael; Huberman, Kety; Viale, Agnes; Pirun, Mono; Socci, Nicholas D.; Bouvier, Nancy; Bauer, Sebastian; Artl, Monika; Schilling, Bastian; Schimming, Tobias; Sucker, Antje; Schwindenhammer, Benjamin; Grabellus, Florian; Speicher, Michael R.; Schaller, Jörg; Hillen, Uwe; Schadendorf, Dirk; Mentzel, Thomas; Cheng, Donavan T.; Wiesner, Thomas; Griewank, Klaus G.

    2015-01-01

    Angiosarcomas are rare malignant mesenchymal tumors of endothelial differentiation. The clinical behavior is usually aggressive and the prognosis for patients with advanced disease is poor with no effective therapies. The genetic bases of these tumors have been partially revealed in recent studies reporting genetic alterations such as amplifications of MYC (primarily in radiation-associated angiosarcomas), inactivating mutations in PTPRB and R707Q hotspot mutations of PLCG1. Here, we performed a comprehensive genomic analysis of 34 angiosarcomas using a clinically-approved, hybridization-based targeted next-generation sequencing assay for 341 well-established oncogenes and tumor suppressor genes. Over half of the angiosarcomas (n = 18, 53%) harbored genetic alterations affecting the MAPK pathway, involving mutations in KRAS, HRAS, NRAS, BRAF, MAPK1 and NF1, or amplifications in MAPK1/CRKL, CRAF or BRAF. The most frequently detected genetic aberrations were mutations in TP53 in 12 tumors (35%) and losses of CDKN2A in 9 tumors (26%). MYC amplifications were generally mutually exclusive of TP53 alterations and CDKN2A loss and were identified in 8 tumors (24%), most of which (n = 7, 88%) arose post-irradiation. Previously reported mutations in PTPRB (n = 10, 29%) and one (3%) PLCG1 R707Q mutation were also identified. Our results demonstrate that angiosarcomas are a genetically heterogeneous group of tumors, harboring a wide range of genetic alterations. The high frequency of genetic events affecting the MAPK pathway suggests that targeted therapies inhibiting MAPK signaling may be promising therapeutic avenues in patients with advanced angiosarcomas. PMID:26440310

  10. Physical Activity and Adherence to Mediterranean Diet Increase Total Antioxidant Capacity: The ATTICA Study

    Directory of Open Access Journals (Sweden)

    Stavros A. Kavouras

    2011-01-01

    Full Text Available We studied the association of physical activity and adherence to the Mediterranean diet, in total antioxidant capacity (TAC. A random sample of 1514 men and 1528 women was selected from Attica region. Physical activity was assessed with a translated version of the validated “International Physical Activity Questionnaire” (iPAQ, and dietary intake through a validated Food Frequency Questionnaire (FFQ. Adherence to the Mediterranean diet was assessed by the MedDietScore that incorporated the inherent characteristics of this diet. TAC was positively correlated with the degree of physical activity (P<.05. TAC was also positively correlated with MedDietScore (r=0.24, P<.001. Stratified analysis by diet status revealed that the most beneficial results were observed to highly active people as compared to inactive, who also followed the Mediterranean diet (288  ±  70 μmol/L, 230  ±  50 μmol/L, resp., after adjusting for various confounders. Increased physical activity and greater adherence to the Mediterranean diet were associated with increased total antioxidant capacity.

  11. Quantitative PCR Profiling of Escherichia coli in Livestock Feces Reveals Increased Population Resilience Relative to Culturable Counts under Temperature Extremes.

    Science.gov (United States)

    Oliver, David M; Bird, Clare; Burd, Emmy; Wyman, Michael

    2016-09-06

    The relationship between culturable counts (CFU) and quantitative PCR (qPCR) cell equivalent counts of Escherichia coli in dairy feces exposed to different environmental conditions and temperature extremes was investigated. Fecal samples were collected in summer and winter from dairy cowpats held under two treatments: field-exposed versus polytunnel-protected. A significant correlation in quantified E. coli was recorded between the qPCR and culture-based methods (r = 0.82). Evaluation of the persistence profiles of E. coli over time revealed no significant difference in the E. coli numbers determined as either CFU or gene copies during the summer for the field-exposed cowpats, whereas significantly higher counts were observed by qPCR for the polytunnel-protected cowpats, which were exposed to higher ambient temperatures. In winter, the qPCR returned significantly higher counts of E. coli for the field-exposed cowpats, thus representing a reversal of the findings from the summer sampling campaign. Results from this study suggest that with increasing time post-defecation and with the onset of challenging environmental conditions, such as extremes in temperature, culture-based counts begin to underestimate the true resilience of viable E. coli populations in livestock feces. This is important not only in the long term as the Earth changes in response to climate-change drivers but also in the short term during spells of extremely cold or hot weather.

  12. The evidence for increased L1 activity in the site of human adult brain neurogenesis.

    Directory of Open Access Journals (Sweden)

    Alexey A Kurnosov

    Full Text Available Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus-the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.

  13. Reveal the response of enzyme activities to heavy metals through in situ zymography.

    Science.gov (United States)

    Duan, Chengjiao; Fang, Linchuan; Yang, Congli; Chen, Weibin; Cui, Yongxing; Li, Shiqing

    2018-07-30

    Enzymes in the soil are vital for assessing heavy metal soil pollution. Although the presence of heavy metals is thought to change the soil enzyme system, the distribution of enzyme activities in heavy metal polluted-soil is still unknown. For the first time, using soil zymography, we analyzed the distribution of enzyme activities of alfalfa rhizosphere and soil surface in the metal-contaminated soil. The results showed that the growth of alfalfa was significantly inhibited, and an impact that was most pronounced in seedling biomass and chlorophyll content. Catalase activity (CAT) in alfalfa decreased with increasing heavy metal concentrations, while malondialdehyde (MDA) content continually increased. The distribution of enzyme activities showed that both phosphatase and β-glucosidase activities were associated with the roots and were rarely distributed throughout the soil. In addition, the total hotspot areas of enzyme activities were the highest in extremely heavy pollution soil. The hotspot areas of phosphatase were 3.4%, 1.5% and 7.1% under none, moderate and extremely heavy pollution treatment, respectively, but increased from 0.1% to 0.9% for β-glucosidase with the increasing pollution levels. Compared with the traditional method of enzyme activities, zymography can directly and accurately reflect the distribution and extent of enzyme activity in heavy metals polluted soil. The results provide an efficient research method for exploring the interaction between enzyme activities and plant rhizosphere. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Breast Fibroadenoma With Increased Activity on 68Ga DOTATATE PET/CT.

    Science.gov (United States)

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Karantanas, Apostolos H; Bagci, Ulas; Patronas, Nicholas J

    2017-02-01

    Fibroadenoma is the most common benign breast tumor in women of reproductive age, carrying little to no risk of breast cancer development. We report on a case of a woman with history of neuroendocrine tumor who on follow-up imaging tests underwent whole-body PET/CT study using Ga DOTATATE. The scan showed increased focal activity in the right breast, which was biopsied revealing a fibroadenoma. The presented data suggests cell surface overexpression of somatostatin receptors by this benign breast tumor. Moreover, this finding emphasizes the need for cautious interpretation of Ga DOTATATE-avid breast lesions that could mimic malignancy in neuroendocrine tumor patients.

  15. Natural and Semisynthetic Analogues of Manadoperoxide B Reveal New Structural Requirements for Trypanocidal Activity

    Science.gov (United States)

    Chianese, Giuseppina; Scala, Fernando; Calcinai, Barbara; Cerrano, Carlo; Dien, Henny A.; Kaiser, Marcel; Tasdemir, Deniz; Taglialatela-Scafati, Orazio

    2013-01-01

    Chemical analysis of the Indonesian sponge Plakortis cfr. lita afforded two new analogues of the potent trypanocidal agent manadoperoxide B (1), namely 12-isomanadoperoxide B (2) and manadoperoxidic acid B (3). These compounds were isolated along with a new short chain dicarboxylate monoester (4), bearing some interesting relationships with the polyketide endoperoxides found in this sponge. Some semi-synthetic analogues of manadoperoxide B (6–8) were prepared and evaluated for antitrypanosomal activity and cytotoxicity. These studies revealed crucial structure–activity relationships that should be taken into account in the design of optimized and simplified endoperoxyketal trypanocidal agents. PMID:23989650

  16. Natural and Semisynthetic Analogues of Manadoperoxide B Reveal New Structural Requirements for Trypanocidal Activity

    Directory of Open Access Journals (Sweden)

    Orazio Taglialatela-Scafati

    2013-08-01

    Full Text Available Chemical analysis of the Indonesian sponge Plakortis cfr. lita afforded two new analogues of the potent trypanocidal agent manadoperoxide B (1, namely 12-isomanadoperoxide B (2 and manadoperoxidic acid B (3. These compounds were isolated along with a new short chain dicarboxylate monoester (4, bearing some interesting relationships with the polyketide endoperoxides found in this sponge. Some semi-synthetic analogues of manadoperoxide B (6–8 were prepared and evaluated for antitrypanosomal activity and cytotoxicity. These studies revealed crucial structure–activity relationships that should be taken into account in the design of optimized and simplified endoperoxyketal trypanocidal agents.

  17. Exogenous Methyl Jasmonate Treatment Increases Glucosinolate Biosynthesis and Quinone Reductase Activity in Kale Leaf Tissue

    Science.gov (United States)

    Ku, Kang-Mo; Jeffery, Elizabeth H.; Juvik, John A.

    2014-01-01

    Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties ‘Dwarf Blue Curled Vates’ and ‘Red Winter’ in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar ‘Red Winter’ in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, Pkale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined increases in phenolics (quercetin and kaempferol) and GS hydrolysis product concentrations rather than by individual products alone. PMID:25084454

  18. Structure of the human protein kinase MPSK1 reveals an atypical activation loop architecture.

    Science.gov (United States)

    Eswaran, Jeyanthy; Bernad, Antonio; Ligos, Jose M; Guinea, Barbara; Debreczeni, Judit E; Sobott, Frank; Parker, Sirlester A; Najmanovich, Rafael; Turk, Benjamin E; Knapp, Stefan

    2008-01-01

    The activation segment of protein kinases is structurally highly conserved and central to regulation of kinase activation. Here we report an atypical activation segment architecture in human MPSK1 comprising a beta sheet and a large alpha-helical insertion. Sequence comparisons suggested that similar activation segments exist in all members of the MPSK1 family and in MAST kinases. The consequence of this nonclassical activation segment on substrate recognition was studied using peptide library screens that revealed a preferred substrate sequence of X-X-P/V/I-phi-H/Y-T*-N/G-X-X-X (phi is an aliphatic residue). In addition, we identified the GTPase DRG1 as an MPSK1 interaction partner and specific substrate. The interaction domain in DRG1 was mapped to the N terminus, leading to recruitment and phosphorylation at Thr100 within the GTPase domain. The presented data reveal an atypical kinase structural motif and suggest a role of MPSK1 regulating DRG1, a GTPase involved in regulation of cellular growth.

  19. An Angiotensin II type 1 receptor activation switch patch revealed through Evolutionary Trace analysis

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Yao, Rong; Ma, Jian-Nong

    2010-01-01

    to be completely resolved. Evolutionary Trace (ET) analysis is a computational method, which identifies clusters of functionally important residues by integrating information on evolutionary important residue variations with receptor structure. Combined with known mutational data, ET predicted a patch of residues......) displayed phenotypes associated with changed activation state, such as increased agonist affinity or basal activity, promiscuous activation, or constitutive internalization highlighting the importance of testing different signaling pathways. We conclude that this evolutionary important patch mediates...

  20. RESEARCH ON INCREASING ACTIVE LIFE OF CUTTING TOOLS

    Directory of Open Access Journals (Sweden)

    Alin STĂNCIOIU

    2012-05-01

    Full Text Available At the exploitation of dies the defections that occur, due mainly to non operating rules of exploration, the improperly conditions of the machine (press in terms of cinematic precision and the wearing elements in relative motion (ram displacement, wearing guides, etc as the incorrect mounting of dies on the press. When installing dies must consider several aspects. Among the techniques used, especially for restoring the active elements in the work area are rectified frontal surfaces, hard chromating, hardening with electric sparks and charging welding. Were restored active profile and size of the work active elements so after reconditioning they corresponded in terms of dimensional precision and resistance to wear, like initial elements

  1. Effectiveness of Corporate Social Media Activities to Increase Relational Outcomes

    DEFF Research Database (Denmark)

    Risius, Marten; Beck, Roman

    2015-01-01

    This study applies social media analytics to investigate the impact of different corporate social media activities on user word of mouth and attitudinal loyalty. We conduct a multilevel analysis of approximately 5 million tweets regarding the main Twitter accounts of 28 large global companies. We...... empirically identify different social media activities in terms of social media management strategies (using social media management tools or the web-frontend client), account types (broadcasting or receiving information), and communicative approaches (conversational or disseminative). We find positive...... effects of social media management tools, broadcasting accounts, and conversational communication on public perception....

  2. Ultrastructural and Molecular Analyses Reveal Enhanced Nucleolar Activity in Medicago truncatula Cells Overexpressing the MtTdp2α Gene

    Science.gov (United States)

    Macovei, Anca; Faè, Matteo; Biggiogera, Marco; de Sousa Araújo, Susana; Carbonera, Daniela; Balestrazzi, Alma

    2018-01-01

    The role of tyrosyl-DNA phosphodiesterase 2 (Tdp2) involved in the repair of 5′-end-blocking DNA lesions is still poorly explored in plants. To gain novel insights, Medicago truncatula suspension cultures overexpressing the MtTdp2α gene (Tdp2α-13C and Tdp2α-28 lines, respectively) and a control (CTRL) line carrying the empty vector were investigated. Transmission electron microscopy (TEM) revealed enlarged nucleoli (up to 44% expansion of the area, compared to CTRL), the presence of nucleolar vacuoles, increased frequency of multinucleolate cells (up to 4.3-fold compared to CTRL) and reduced number of ring-shaped nucleoli in Tdp2α-13C and Tdp2α-28 lines. Ultrastructural data suggesting for enhanced nucleolar activity in MtTdp2α-overexpressing lines were integrated with results from bromouridine incorporation. The latter revealed an increase of labeled transcripts in both Tdp2α-13C and Tdp2α-28 cells, within the nucleolus and in the extra-nucleolar region. MtTdp2α-overexpressing cells showed tolerance to etoposide, a selective inhibitor of DNA topoisomerase II, as evidenced by DNA diffusion assay. TEM analysis revealed etoposide-induced rearrangements within the nucleolus, resembling the nucleolar caps observed in animal cells under transcription impairment. Based on these findings it is evident that MtTdp2α-overexpression enhances nucleolar activity in plant cells. PMID:29868059

  3. Ultrastructural and Molecular Analyses Reveal Enhanced Nucleolar Activity in Medicago truncatula Cells Overexpressing the MtTdp2α Gene

    Directory of Open Access Journals (Sweden)

    Anca Macovei

    2018-05-01

    Full Text Available The role of tyrosyl-DNA phosphodiesterase 2 (Tdp2 involved in the repair of 5′-end-blocking DNA lesions is still poorly explored in plants. To gain novel insights, Medicago truncatula suspension cultures overexpressing the MtTdp2α gene (Tdp2α-13C and Tdp2α-28 lines, respectively and a control (CTRL line carrying the empty vector were investigated. Transmission electron microscopy (TEM revealed enlarged nucleoli (up to 44% expansion of the area, compared to CTRL, the presence of nucleolar vacuoles, increased frequency of multinucleolate cells (up to 4.3-fold compared to CTRL and reduced number of ring-shaped nucleoli in Tdp2α-13C and Tdp2α-28 lines. Ultrastructural data suggesting for enhanced nucleolar activity in MtTdp2α-overexpressing lines were integrated with results from bromouridine incorporation. The latter revealed an increase of labeled transcripts in both Tdp2α-13C and Tdp2α-28 cells, within the nucleolus and in the extra-nucleolar region. MtTdp2α-overexpressing cells showed tolerance to etoposide, a selective inhibitor of DNA topoisomerase II, as evidenced by DNA diffusion assay. TEM analysis revealed etoposide-induced rearrangements within the nucleolus, resembling the nucleolar caps observed in animal cells under transcription impairment. Based on these findings it is evident that MtTdp2α-overexpression enhances nucleolar activity in plant cells.

  4. Increased expression of T-helper cell activation markers in ...

    African Journals Online (AJOL)

    Ehab

    expression of these activation markers would be of value in monitoring asthma severity and the response to ... Key words: Children, atopic asthma, T-helper cell subsets, glucocorticoid inhalation, lower respiratory infections, CD45RO ...... budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma.

  5. Counselling increases physical activity behaviour nine weeks after rehabilitation

    NARCIS (Netherlands)

    van der Ploeg, H P; Streppel, K R M; van der Beek, A J; van der Woude, L H V; Vollenbroek-Hutten, M M R; van Harten, W H; van Mechelen, W

    BACKGROUND: For people with disabilities, a physically active lifestyle can reduce the risk of secondary health problems and improve overall functioning. OBJECTIVES: To determine the effects of the sport stimulation programme "rehabilitation and sports" (R&S) and R&S combined with the daily physical

  6. Compensation in resting metabolism for experimentally increased activity

    NARCIS (Netherlands)

    Deerenberg, C; Overkamp, GJF; Visser, GH; Daan, S; Heldmaier, G.

    1998-01-01

    To study zebra finch allocation of energy to day and night at two different workloads, we assessed the daily energy turnover from: (1) metabolizable energy of the food, and (2) doubly-labeled water. In both experiments we imposed two levels of activity on captive zebra finches (Taeniopygia guttata),

  7. Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS.

    Science.gov (United States)

    Ruppenthal, Sabrina; Kleiner, Helga; Nolte, Florian; Fabarius, Alice; Hofmann, Wolf-Karsten; Nowak, Daniel; Seifarth, Wolfgang

    2018-01-01

    ESPL1/separase, a cysteine endopeptidase, is a key player in centrosome duplication and mitotic sister chromatid separation. Aberrant expression and/or altered separase proteolytic activity are associated with centrosome amplification, aneuploidy, tumorigenesis and disease progression. Since centrosome alterations are a common and early detectable feature in patients with myelodysplastic syndrome (MDS) and cytogenetic aberrations play an important role in disease risk stratification, we examined separase activity on single cell level in 67 bone marrow samples obtained from patients with MDS, secondary acute myeloid leukemia (sAML), de novo acute myeloid leukemia (AML) and healthy controls by a flow cytometric separase activity assay. The separase activity distribution (SAD) value, a calculated measure for the occurrence of cells with prominent separase activity within the analyzed sample, was tested for correlation with the centrosome, karyotype and gene mutation status. We found higher SAD values in bone marrow cells of sAML patients than in corresponding cells of MDS patients. This concurred with an increased incidence of aberrant centrosome phenotypes in sAML vs. MDS samples. No correlation was found between SAD values and the karyotype/gene mutation status. During follow-up of four MDS patients we observed increasing SAD values after transformation to sAML, in two patients SAD values decreased during azacitidine therapy. Cell culture experiments employing MDS-L cells as an in vitro model of MDS revealed that treatment with rigosertib, a PLK1 inhibitor and therapeutic drug known to induce G2/M arrest, results in decreased SAD values. In conclusion, the appearance of cells with unusual high separase activity levels, as indicated by increased SAD values, concurs with the transformation of MDS to sAML and may reflect separase dysregulation potentially contributing to clonal evolution during MDS progression. Separase activity measurement may therefore be useful as a

  8. Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity.

    Science.gov (United States)

    Riès, Stephanie K; Dhillon, Rummit K; Clarke, Alex; King-Stephens, David; Laxer, Kenneth D; Weber, Peter B; Kuperman, Rachel A; Auguste, Kurtis I; Brunner, Peter; Schalk, Gerwin; Lin, Jack J; Parvizi, Josef; Crone, Nathan E; Dronkers, Nina F; Knight, Robert T

    2017-06-06

    Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70-150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain.

  9. Trunk muscle activity increases with unstable squat movements.

    Science.gov (United States)

    Anderson, Kenneth; Behm, David G

    2005-02-01

    The objective of this study was to determine differences in electromyographic (EMG) activity of the soleus (SOL), vastus lateralis (VL), biceps femoris (BF), abdominal stabilizers (AS), upper lumbar erector spinae (ULES), and lumbo-sacral erector spinae (LSES) muscles while performing squats of varied stability and resistance. Stability was altered by doing the squat movement on a Smith machine, a free squat, and while standing on two balance discs. Fourteen male subjects performed the movements. Activities of the SOL, AS, ULES, and LSES were highest during the unstable squat and lowest with the Smith machine protocol (p squats on unstable surfaces may permit a training adaptation of the trunk muscles responsible for supporting the spinal column (i.e., erector spinae) as well as the muscles most responsible for maintaining posture (i.e., SOL).

  10. Whole-brain activity maps reveal stereotyped, distributed networks for visuomotor behavior.

    Science.gov (United States)

    Portugues, Ruben; Feierstein, Claudia E; Engert, Florian; Orger, Michael B

    2014-03-19

    Most behaviors, even simple innate reflexes, are mediated by circuits of neurons spanning areas throughout the brain. However, in most cases, the distribution and dynamics of firing patterns of these neurons during behavior are not known. We imaged activity, with cellular resolution, throughout the whole brains of zebrafish performing the optokinetic response. We found a sparse, broadly distributed network that has an elaborate but ordered pattern, with a bilaterally symmetrical organization. Activity patterns fell into distinct clusters reflecting sensory and motor processing. By correlating neuronal responses with an array of sensory and motor variables, we find that the network can be clearly divided into distinct functional modules. Comparing aligned data from multiple fish, we find that the spatiotemporal activity dynamics and functional organization are highly stereotyped across individuals. These experiments systematically reveal the functional architecture of neural circuits underlying a sensorimotor behavior in a vertebrate brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Xanthene derivatives increase glucose utilization through activation of LKB1-dependent AMP-activated protein kinase.

    Directory of Open Access Journals (Sweden)

    Yonghoon Kwon

    Full Text Available 5' AMP-activated protein kinase (AMPK is a highly conserved serine-threonine kinase that regulates energy expenditure by activating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. Therefore AMPK activators are considered to be drug targets for treatment of metabolic diseases such as diabetes mellitus. To identify novel AMPK activators, we screened xanthene derivatives. We determined that the AMPK activators 9H-xanthene-9-carboxylic acid {2,2,2-trichloro-1-[3-(3-nitro-phenyl-thioureido]-ethyl}-amide (Xn and 9H-xanthene-9-carboxylic acid {2,2,2-trichloro-1-[3-(3-cyano-phenyl-thioureido]-ethyl}-amide (Xc elevated glucose uptake in L6 myotubes by stimulating translocation of glucose transporter type 4 (GLUT4. Treatment with the chemical AMPK inhibitor compound C and infection with dominant-negative AMPKa2-virus inhibited AMPK phosphorylation and glucose uptake in myotubes induced by either Xn or Xc. Of the two major upstream kinases of AMPK, we found that Xn and Xc showed LKB1 dependency by knockdown of STK11, an ortholog of human LKB1. Single intravenous administration of Xn and Xc to high-fat diet-induced diabetic mice stimulated AMPK phosphorylation of skeletal muscle and improved glucose tolerance. Taken together, these results suggest that Xn and Xc regulate glucose homeostasis through LKB1-dependent AMPK activation and that the compounds are potential candidate drugs for the treatment of type 2 diabetes mellitus.

  12. Motivational Interviewing to Increase Physical Activity in Breast Cancer Survivors

    Science.gov (United States)

    2011-05-01

    impact of physical activity on depressive symptoms, fatigue, and aerobic fitness over time. 4 BODY TRAINING ACCOMPLISHMENTS The SOW outlined 5...not count fruit drinks like Kooi-Aid, lemonade, Hi-C, cranberry juice drink, Tang, and Twister. Include juice you drank at all mealtimes and between...5. I had trouble keeping my mind on what I was D D D D doing 6. I felt depressed D D D D 7. I felt that everything I did was an effort D D D D

  13. Inter-species activity correlations reveal functional correspondences between monkey and human brain areas

    Science.gov (United States)

    Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G.; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A.; Vanduffel, Wim

    2012-01-01

    Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. In cases where functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assess similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by means of temporal correlation. Using natural vision data, we reveal regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This novel framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models. PMID:22306809

  14. Common brain regions underlying different arithmetic operations as revealed by conjunct fMRI-BOLD activation.

    Science.gov (United States)

    Fehr, Thorsten; Code, Chris; Herrmann, Manfred

    2007-10-03

    The issue of how and where arithmetic operations are represented in the brain has been addressed in numerous studies. Lesion studies suggest that a network of different brain areas are involved in mental calculation. Neuroimaging studies have reported inferior parietal and lateral frontal activations during mental arithmetic using tasks of different complexities and using different operators (addition, subtraction, etc.). Indeed, it has been difficult to compare brain activation across studies because of the variety of different operators and different presentation modalities used. The present experiment examined fMRI-BOLD activity in participants during calculation tasks entailing different arithmetic operations -- addition, subtraction, multiplication and division -- of different complexities. Functional imaging data revealed a common activation pattern comprising right precuneus, left and right middle and superior frontal regions during all arithmetic operations. All other regional activations were operation specific and distributed in prominently frontal, parietal and central regions when contrasting complex and simple calculation tasks. The present results largely confirm former studies suggesting that activation patterns due to mental arithmetic appear to reflect a basic anatomical substrate of working memory, numerical knowledge and processing based on finger counting, and derived from a network originally related to finger movement. We emphasize that in mental arithmetic research different arithmetic operations should always be examined and discussed independently of each other in order to avoid invalid generalizations on arithmetics and involved brain areas.

  15. Transient increase in phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol trisphosphate during activation of human neutrophils

    International Nuclear Information System (INIS)

    Traynor-Kaplan, A.E.; Thompson, B.L.; Harris, A.L.; Taylor, P.; Omann, G.M.; Sklar, L.A.

    1989-01-01

    We recently showed that phosphatidylinositol trisphosphate (PIP3) was present in a unique lipid fraction generated in neutrophils during activation. Here, we demonstrate that the band containing this fraction isolated from thin layer chromatography consists primarily of PIP3 and that only small amounts of radiolabeled PIP3 exist prior to activation. In addition, high performance liquid chromatography of deacylated phospholipids from stimulated cells reveals an increase in a fraction eluting ahead of glycerophosphoinositol 4,5-P2. After removal of the glycerol we found that it coeluted with inositol 1,3,4-P3 when resubjected to high performance liquid chromatography. Thus, we have detected a second, novel form of phosphatidylinositol bisphosphate in activated neutrophils, PI-(3,4)P2. The elevation of PIP3 through the formyl peptide receptor is blocked by pretreatment with pertussis toxin, implicating mediation of the increase in PIP3 by a guanosine triphosphate-binding (G) protein. The rise in PIP3 is not secondary to calcium elevation. Buffering the rise in intracellular calcium did not diminish the increase in PIP3. The elevation of PIP3 appears to occur during activation with physiological agonists, its level varying with the degree of activation. Leukotriene B4, which elicits many of the same responses as stimulation of the formyl peptide receptor but with minimal oxidant production, stimulates a much attenuated rise in PIP3. Isoproterenol, which inhibits oxidant production also reduces the rise in PIP3. Hence formation of PI(3,4)P2 and PIP3 (presumed to be PI(3,4,5)P3) correlates closely with the early events of neutrophil activation

  16. Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma.

    Science.gov (United States)

    Yoo, Byoung Kwon; Santhekadur, Prasanna K; Gredler, Rachel; Chen, Dong; Emdad, Luni; Bhutia, Sujit; Pannell, Lewis; Fisher, Paul B; Sarkar, Devanand

    2011-05-01

    There is virtually no effective treatment for advanced hepatocellular carcinoma (HCC) and novel targets need to be identified to develop effective treatment. We recently documented that the oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis. Employing yeast two-hybrid assay and coimmunoprecipitation followed by mass spectrometry, we identified staphylococcal nuclease domain containing 1 (SND1), a nuclease in the RNA-induced silencing complex (RISC) facilitating RNAi-mediated gene silencing, as an AEG-1 interacting protein. Coimmunoprecipitation and colocalization studies confirmed that AEG-1 is also a component of RISC and both AEG-1 and SND1 are required for optimum RISC activity facilitating small interfering RNA (siRNA) and micro RNA (miRNA)-mediated silencing of luciferase reporter gene. In 109 human HCC samples SND1 was overexpressed in ≈74% cases compared to normal liver. Correspondingly, significantly higher RISC activity was observed in human HCC cells compared to immortal normal hepatocytes. Increased RISC activity, conferred by AEG-1 or SND1, resulted in increased degradation of tumor suppressor messenger RNAs (mRNAs) that are target of oncomiRs. Inhibition of enzymatic activity of SND1 significantly inhibited proliferation of human HCC cells. As a corollary, stable overexpression of SND1 augmented and siRNA-mediated inhibition of SND1 abrogated growth of human HCC cells in vitro and in vivo, thus revealing a potential role of SND1 in hepatocarcinogenesis. We unravel a novel mechanism that overexpression of AEG-1 and SND1 leading to increased RISC activity might contribute to hepatocarcinogenesis. Targeted inhibition of SND1 enzymatic activity might be developed as an effective therapy for HCC. Copyright © 2011 American Association for the Study of Liver Diseases.

  17. Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

    Directory of Open Access Journals (Sweden)

    Kristina Kirschner

    2015-03-01

    Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

  18. Identity of active methanotrophs in landfill cover soil as revealed by DNA-stable isotope probing.

    Science.gov (United States)

    Cébron, Aurélie; Bodrossy, Levente; Chen, Yin; Singer, Andrew C; Thompson, Ian P; Prosser, James I; Murrell, J Colin

    2007-10-01

    A considerable amount of methane produced during decomposition of landfill waste can be oxidized in landfill cover soil by methane-oxidizing bacteria (methanotrophs) thus reducing greenhouse gas emissions to the atmosphere. The identity of active methanotrophs in Roscommon landfill cover soil, a slightly acidic peat soil, was assessed by DNA-stable isotope probing (SIP). Landfill cover soil slurries were incubated with (13)C-labelled methane and under either nutrient-rich nitrate mineral salt medium or water. The identity of active methanotrophs was revealed by analysis of (13)C-labelled DNA fractions. The diversity of functional genes (pmoA and mmoX) and 16S rRNA genes was analyzed using clone libraries, microarrays and denaturing gradient gel electrophoresis. 16S rRNA gene analysis revealed that the cover soil was mainly dominated by Type II methanotrophs closely related to the genera Methylocella and Methylocapsa and to Methylocystis species. These results were supported by analysis of mmoX genes in (13)C-DNA. Analysis of pmoA gene diversity indicated that a significant proportion of active bacteria were also closely related to the Type I methanotrophs, Methylobacter and Methylomonas species. Environmental conditions in the slightly acidic peat soil from Roscommon landfill cover allow establishment of both Type I and Type II methanotrophs.

  19. Myeloperoxidase activity is increased in gingival crevicular fluid and whole saliva after fixed orthodontic appliance activation.

    Science.gov (United States)

    Marcaccini, Andrea M; Amato, Patricia A F; Leão, Fernanda V; Gerlach, Raquel F; Ferreira, Jose T L

    2010-11-01

    Orthodontic tooth movement uses mechanical forces that result in inflammation in the first days. Myeloperoxidase (MPO) is an enzyme found in polymorphonuclear neutrophil (PMN) granules, and it is used to estimate the number of PMN granules in tissues. So far, MPO has not been used to study the inflammatory alterations after the application of orthodontic tooth movement forces. The aim of this study was to determine MPO activity in the gingival crevicular fluid (GCF) and saliva (whole stimulated saliva) of orthodontic patients at different time points after fixed appliance activation. MPO was determined in the GCF and collected by means of periopaper from the saliva of 14 patients with orthodontic fixed appliances. GCF and saliva samples were collected at baseline, 2 hours, and 7 and 14 days after application of the orthodontic force. Mean MPO activity was increased in both the GCF and saliva of orthodontic patients at 2 hours after appliance activation (P orthodontic force probably results in the increased MPO level observed at this time point. MPO might be a good marker to assess inflammation in orthodontic movement; it deserves further studies in orthodontic therapy. Copyright © 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  20. Collaborative activity between parietal and dorso-lateral prefrontal cortex in dynamic spatial working memory revealed by fMRI.

    Science.gov (United States)

    Diwadkar, V A; Carpenter, P A; Just, M A

    2000-07-01

    Functional MRI was used to determine how the constituents of the cortical network subserving dynamic spatial working memory respond to two types of increases in task complexity. Participants mentally maintained the most recent location of either one or three objects as the three objects moved discretely in either a two- or three-dimensional array. Cortical activation in the dorsolateral prefrontal (DLPFC) and the parietal cortex increased as a function of the number of object locations to be maintained and the dimensionality of the display. An analysis of the response characteristics of the individual voxels showed that a large proportion were activated only when both the variables imposed the higher level of demand. A smaller proportion were activated specifically in response to increases in task demand associated with each of the independent variables. A second experiment revealed the same effect of dimensionality in the parietal cortex when the movement of objects was signaled auditorily rather than visually, indicating that the additional representational demands induced by 3-D space are independent of input modality. The comodulation of activation in the prefrontal and parietal areas by the amount of computational demand suggests that the collaboration between areas is a basic feature underlying much of the functionality of spatial working memory. Copyright 2000 Academic Press.

  1. Sympathetic network drive during water deprivation does not increase respiratory or cardiac rhythmic sympathetic nerve activity.

    Science.gov (United States)

    Holbein, Walter W; Toney, Glenn M

    2013-06-15

    Effects of water deprivation on rhythmic bursting of sympathetic nerve activity (SNA) were investigated in anesthetized, bilaterally vagotomized, euhydrated (control) and 48-h water-deprived (WD) rats (n = 8/group). Control and WD rats had similar baseline values of mean arterial pressure, heart rate, end-tidal CO2, and central respiratory drive. Although integrated splanchnic SNA (sSNA) was greater in WD rats than controls (P analysis of respiratory rhythmic bursting of sSNA revealed that inspiratory rhythmic burst amplitude was actually smaller (P analysis revealed that water deprivation had no effect on either the amplitude or periodicity of the cardiac rhythmic oscillation of sSNA. Collectively, these data indicate that the increase of sSNA produced by water deprivation is not attributable to either increased respiratory or cardiac rhythmic burst discharge. Thus the sympathetic network response to acute water deprivation appears to differ from that of chronic sympathoexcitation in neurogenic forms of arterial hypertension, where increased respiratory rhythmic bursting of SNA and baroreflex adaptations have been reported.

  2. Effects of sport activities on increasing preschool children's creativity

    Directory of Open Access Journals (Sweden)

    Mehdi Shahbazi

    2012-10-01

    Full Text Available Torrance tests of creative thinking have been widely used to measure the impact of different items such as creativity on different groups of children. In this study, we perform an empirical study to measure the effects of endurance, power-based and flexibility on a group of children's creativity, originality and flexibility. The study chooses a sample of 341 from 2978 preschool children and distributes a questionnaire among them where 153 were female and 188 of them were male. Cronbach alpha for creativity, originality and fluency were calculated as 0.814, 0.822 and 0.788, respectively. The results of our study indicate that there are some positive and meaningful relationship among three components of creativity, originality and fluency before and after accomplishing test. The impact of test was measured for three types of sport activities including endurance, power-based and flexibility tests. After applying 32 sessions of sporting games, flexibility games represent a mean value of 32.40, which is higher than the other two tests and it maintains meaningful value compared with two other sporting tests of endurance and power base tests.

  3. Application of Pilates principles increases paraspinal muscle activation.

    Science.gov (United States)

    Andrade, Letícia Souza; Mochizuki, Luís; Pires, Flávio Oliveira; da Silva, Renato André Sousa; Mota, Yomara Lima

    2015-01-01

    To analyze the effect of Pilates principles on the EMG activity of abdominal and paraspinal muscles on stable and unstable surfaces. Surface EMG data about the rectus abdominis (RA), iliocostalis (IL) and lumbar multifidus (MU) of 19 participants were collected while performing three repetitions of a crunch exercise in the following conditions: 1) with no Pilates technique and stable surface (nP + S); 2) with no Pilates technique and unstable surface (nP + U); 3) with Pilates technique and stable surface (P + S); 4) with Pilates and unstable surface (P + U). The EMG Fanalysis was conducted using a custom-made Matlab(®) 10. There was no condition effect in the RA iEMG with stable and unstable surfaces (F(1,290) = 0 p = 0.98) and with and without principles (F(1,290) = 1.2 p = 0.27). IL iEMG was higher for the stable surface condition (F(1,290) = 32.3 p Pilates principles (F(1,290) = 21.9 p Pilates principles (F(1,290) = 84.9 p < 0.001). Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity

    Directory of Open Access Journals (Sweden)

    Monika Dabrzalska

    2017-02-01

    Full Text Available The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer—methylene blue (MB. As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines.

  5. SSU rRNA reveals a sequential increase in shell complexity among the euglyphid testate amoebae (Rhizaria: Euglyphida)

    DEFF Research Database (Denmark)

    Lara, Enrique; Heger, Thierry J; Mitchell, Edward A D

    2007-01-01

    The existing data on the molecular phylogeny of filose testate amoebae from order Euglyphida has revealed contradictions between traditional morphological classification and SSU rRNA phylogeny and, moreover, the position of several important genera remained unknown. We therefore carried out a stu...

  6. Prices dip, activity increases in unrestricted uranium market

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    April's activity in the restricted uranium market fluctuated in the same range as that observed in March. At the same time, NUKEM detects a weakening of prices in the unrestricted market to $7.45-$7.65. Unrestricted buyers seem to have detected lower prices as well; much of the new demand noted this month emerged in the unrestricted segment of the market. With this issue, NUKEM inaugurates a new market statistic. To better follow developments in the conversion market, we will report a spot price range for conversion services. This price measure will be derived in a manner analogous to NUKEM's other spot market price ranges. We will continue to publish the current NUKEM price range for new contracts for a few months. If you wish to retain the old conversion contract price range in future editions, please contact our US office. Four deals for near term delivery occurred in the uranium market in April, resulting in spot market transaction volume of 2.5 million lbs U3O8 equivalent. In the first week, a US non-utility purchased a small quantity of enriched uranium product from an intermediary in a spot transaction representing about 75,000 lbs U3O8. The second week saw the stealthy purchase of Portland General Electric's inventory of natural and enriched uranium. The buyer of PGE's 1.1 million lbs U3O8 equivalent has achieved an unusual degree of anonymity. Also during the second week, a US utility bought a small quantity of enriched uranium containing less than 25,000 lbs natural U3O8 equivalent

  7. Peptidomic analysis reveals proteolytic activity of kefir microorganisms on bovine milk proteins

    Science.gov (United States)

    Dallas, David C.; Citerne, Florine; Tian, Tian; Silva, Vitor L. M.; Kalanetra, Karen M.; Frese, Steven A.; Robinson, Randall C.; Mills, David A.; Barile, Daniela

    2015-01-01

    Scope The microorganisms that make up kefir grains are well known for lactose fermentation, but the extent to which they hydrolyze and consume milk proteins remains poorly understood. Peptidomics technologies were used to examine the proteolytic activity of kefir grains on bovine milk proteins. Methods and results Gel electrophoresis revealed substantial digestion of milk proteins by kefir grains, with mass spectrometric analysis showing the release of 609 protein fragments and alteration of the abundance of >1,500 peptides that derived from 27 milk proteins. Kefir contained 25 peptides identified from the literature as having biological activity, including those with antihypertensive, antimicrobial, immunomodulatory, opioid and anti-oxidative functions. 16S rRNA and shotgun metagenomic sequencing identified the principle taxa in the culture as Lactobacillus species. Conclusion The model kefir sample contained thousands of protein fragments released in part by kefir microorganisms and in part by native milk proteases. PMID:26616950

  8. Peptidomic analysis reveals proteolytic activity of kefir microorganisms on bovine milk proteins.

    Science.gov (United States)

    Dallas, David C; Citerne, Florine; Tian, Tian; Silva, Vitor L M; Kalanetra, Karen M; Frese, Steven A; Robinson, Randall C; Mills, David A; Barile, Daniela

    2016-04-15

    The microorganisms that make up kefir grains are well known for lactose fermentation, but the extent to which they hydrolyze and consume milk proteins remains poorly understood. Peptidomics technologies were used to examine the proteolytic activity of kefir grains on bovine milk proteins. Gel electrophoresis revealed substantial digestion of milk proteins by kefir grains, with mass spectrometric analysis showing the release of 609 protein fragments and alteration of the abundance of >1500 peptides that derived from 27 milk proteins. Kefir contained 25 peptides identified from the literature as having biological activity, including those with antihypertensive, antimicrobial, immunomodulatory, opioid and anti-oxidative functions. 16S rRNA and shotgun metagenomic sequencing identified the principle taxa in the culture as Lactobacillus species. The model kefir sample contained thousands of protein fragments released in part by kefir microorganisms and in part by native milk proteases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase

    Directory of Open Access Journals (Sweden)

    Abrahim Noor

    2012-11-01

    Full Text Available Abstract Background Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7. Methods The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase assays in MCF-7 cells. Results Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml. Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase. Conclusions Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide

  10. Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase.

    Science.gov (United States)

    Abrahim, Noor Nazirahanie; Kanthimathi, M S; Abdul-Aziz, Azlina

    2012-11-15

    Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7. The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane) and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) assays in MCF-7 cells. Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml). Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase. Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide dismutase in the treated cells could alter the antioxidant defense

  11. Glycoprotein profiles of macrophages at different stages of activation as revealed by lectin binding after electrophoretic separation.

    Science.gov (United States)

    Irimura, T; North, S M; Nicolson, G L

    1987-01-01

    Glycoprotein profiles of rat macrophages (M phi) at different stages of activation were studied by examining the reactivity of various lectins to the glycoproteins separated by polyacrylamide gel electrophoresis. Ricinus communis agglutinin 1 (RCA1) revealed several components including glycoproteins of Mr 160 kDa and 65 kDa prominent in resident M phi. A pokeweed mitogen (PWM) isolectin, Pa-4, recognizes branched poly(N-acetyllactosamine)-type carbohydrate chains, and revealed a significant increase in glycoproteins of Mr ranging from 70 kDa to 150 kDa on thioglycolate-elicited M phi. Increased reactivity of PWM to thioglycolate-elicited M phi was observed by direct binding of 125I-labeled Pa-4 to intact or glutaraldehyde-fixed M phi. Histochemical staining of formaldehyde-fixed M phi in vitro with biotinylated Pa-4 was consistent with the gel analysis, that is, resident M phi had no reactivity while thioglycolate-elicited M phi showed slight reactivity. Alveolar and intratumoral M phi bound more Pa-4 than resident or thioglycolate-elicited M phi. The PWM isolectin may therefore serve as a marker for an early stage of M phi activation.

  12. SNOW AVALANCHE ACTIVITY IN PARÂNG SKI AREA REVEALED BY TREE-RINGS

    Directory of Open Access Journals (Sweden)

    F. MESEȘAN

    2014-11-01

    Full Text Available Snow Avalanche Activity in Parâng Ski Area Revealed by Tree-Rings. Snow avalanches hold favorable conditions to manifest in Parâng Mountains but only one event is historically known, without destructive impact upon infrastructure or fatalities and this region wasn’t yet the object of avalanche research. The existing ski infrastructure of Parâng resort located in the west of Parâng Mountains is proposed to be extended in the steep slopes of subalpine area. Field evidence pinpoints that these steep slopes were affected by snow avalanches in the past. In this study we analyzed 11 stem discs and 31 increment cores extracted from 22 spruces (Picea abies (L. Karst impacted by avalanches, in order to obtain more information about past avalanches activity. Using the dendrogeomorphological approach we found 13 avalanche events that occurred along Scărița avalanche path, since 1935 until 2012, nine of them produced in the last 20 years. The tree-rings data inferred an intense snow avalanche activity along this avalanche path. This study not only calls for more research in the study area but also proves that snow avalanches could constitute an important restrictive factor for the tourism infrastructure and related activities in the area. It must be taken into consideration by the future extension of tourism infrastructure. Keywords: snow avalanche, Parâng Mountains, dendrogeomorphology, ski area.

  13. Presbycusis Disrupts Spontaneous Activity Revealed by Resting-State Functional MRI

    Directory of Open Access Journals (Sweden)

    Yu-Chen Chen

    2018-03-01

    Full Text Available Purpose: Presbycusis, age-related hearing loss, is believed to involve neural changes in the central nervous system, which is associated with an increased risk of cognitive impairment. The goal of this study was to determine if presbycusis disrupted spontaneous neural activity in specific brain areas involved in auditory processing, attention and cognitive function using resting-state functional magnetic resonance imaging (fMRI approach.Methods: Hearing and resting-state fMRI measurements were obtained from 22 presbycusis patients and 23 age-, sex- and education-matched healthy controls. To identify changes in spontaneous neural activity associated with age-related hearing loss, we compared the amplitude of low-frequency fluctuations (ALFF and regional homogeneity (ReHo of fMRI signals in presbycusis patients vs. controls and then determined if these changes were linked to clinical measures of presbycusis.Results: Compared with healthy controls, presbycusis patients manifested decreased spontaneous activity mainly in the superior temporal gyrus (STG, parahippocampal gyrus (PHG, precuneus and inferior parietal lobule (IPL as well as increased neural activity in the middle frontal gyrus (MFG, cuneus and postcentral gyrus (PoCG. A significant negative correlation was observed between ALFF/ReHo activity in the STG and average hearing thresholds in presbycusis patients. Increased ALFF/ReHo activity in the MFG was positively correlated with impaired Trail-Making Test B (TMT-B scores, indicative of impaired cognitive function involving the frontal lobe.Conclusions: Presbycusis patients have disrupted spontaneous neural activity reflected by ALFF and ReHo measurements in several brain regions; these changes are associated with specific cognitive performance and speech/language processing. These findings mainly emphasize the crucial role of aberrant resting-state ALFF/ReHo patterns in presbycusis patients and will lead to a better understanding of the

  14. Presbycusis Disrupts Spontaneous Activity Revealed by Resting-State Functional MRI.

    Science.gov (United States)

    Chen, Yu-Chen; Chen, Huiyou; Jiang, Liang; Bo, Fan; Xu, Jin-Jing; Mao, Cun-Nan; Salvi, Richard; Yin, Xindao; Lu, Guangming; Gu, Jian-Ping

    2018-01-01

    Purpose : Presbycusis, age-related hearing loss, is believed to involve neural changes in the central nervous system, which is associated with an increased risk of cognitive impairment. The goal of this study was to determine if presbycusis disrupted spontaneous neural activity in specific brain areas involved in auditory processing, attention and cognitive function using resting-state functional magnetic resonance imaging (fMRI) approach. Methods : Hearing and resting-state fMRI measurements were obtained from 22 presbycusis patients and 23 age-, sex- and education-matched healthy controls. To identify changes in spontaneous neural activity associated with age-related hearing loss, we compared the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of fMRI signals in presbycusis patients vs. controls and then determined if these changes were linked to clinical measures of presbycusis. Results : Compared with healthy controls, presbycusis patients manifested decreased spontaneous activity mainly in the superior temporal gyrus (STG), parahippocampal gyrus (PHG), precuneus and inferior parietal lobule (IPL) as well as increased neural activity in the middle frontal gyrus (MFG), cuneus and postcentral gyrus (PoCG). A significant negative correlation was observed between ALFF/ReHo activity in the STG and average hearing thresholds in presbycusis patients. Increased ALFF/ReHo activity in the MFG was positively correlated with impaired Trail-Making Test B (TMT-B) scores, indicative of impaired cognitive function involving the frontal lobe. Conclusions : Presbycusis patients have disrupted spontaneous neural activity reflected by ALFF and ReHo measurements in several brain regions; these changes are associated with specific cognitive performance and speech/language processing. These findings mainly emphasize the crucial role of aberrant resting-state ALFF/ReHo patterns in presbycusis patients and will lead to a better understanding of the

  15. Revealing hidden effect of earthworm on C distribution and enzyme activity

    Science.gov (United States)

    Razavi, Bahar S.; Hoang, Duyen; Kuzyakov, Yakov

    2017-04-01

    Despite its importance for terrestrial nutrient and carbon cycling, the spatial organization and localization of microbial activity in soil and in biopores is poorly understood. We hypothesized that biopores created by earthworm play a critical role in reducing the gap of SOM input and microbial activities between topsoil and subsoil. Accordingly, Carbon (C) allocation by earthworms was related to enzyme distribution along soil profile. For the first time we visualized spatial distribution of enzyme activities (β-glucosidase, chitinase and acid phosphatase) and C allocation (by 14C imaging) in earthworm biopores in topsoil and subsoil. Soil zymography (an in situ method for the analysis of the two-dimensional distribution of enzyme activity in soil) was accompanied with 14C imaging (a method that enables to trace distribution of litter and C in soil profile) to visualize change of enzyme activities along with SOM incorporation by earthworms from topsoil to subsoil. Experiment was set up acquiring rhizoboxes (9×1×50 cm) filled up with fresh soil and 3 earthworms (L. terrestris), which were then layered with 14C-labeled plant-litter of 0.3 MBq on the soil surface. 14C imaging and zymography have been carried out after one month. Activities of all enzymes regardless of their nutrient involvement (C, N, P) were higher in the biopores than in bulk soil, but the differences were larger in topsoil compared to subsoil. Among three enzymes, Phosphatase activity was 4-times higher in the biopore than in the bulk soil. Phosphatase activity was closely associated with edge of burrows and correlate positively with 14C activity. These results emphasized especial contribution of hotspheres such as biopores to C allocation in subsoil - which is limited in C input and nutrients - and in stimulation of microbial and enzymatic activity by input of organic residues, e.g. by earthworms. In conclusion, biopore increased enzymatic mobilization of nutrients (e.g. P) inducing allocation

  16. Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Jonathan Wirsich

    2016-01-01

    In rTLE patients, we found a widespread hypercorrelated functional network. Network communication analysis revealed greater unspecific branching of the shortest path (search information in the structural connectome and a higher global correlation between the structural and functional connectivity for the patient group. We also found evidence for a preserved structural rich-club in the patient group. In sum, global augmentation of structure-function correlation might be linked to a smaller functional repertoire in rTLE patients, while sparing the central core of the brain which may represent a pathway that facilitates the spread of seizures.

  17. Lost for emotion words: What motor and limbic brain activity reveals about autism and semantic theory

    Science.gov (United States)

    Moseley, Rachel L.; Shtyrov, Yury; Mohr, Bettina; Lombardo, Michael V.; Baron-Cohen, Simon; Pulvermüller, Friedemann

    2015-01-01

    Autism spectrum conditions (ASC) are characterised by deficits in understanding and expressing emotions and are frequently accompanied by alexithymia, a difficulty in understanding and expressing emotion words. Words are differentially represented in the brain according to their semantic category and these difficulties in ASC predict reduced activation to emotion-related words in limbic structures crucial for affective processing. Semantic theories view ‘emotion actions’ as critical for learning the semantic relationship between a word and the emotion it describes, such that emotion words typically activate the cortical motor systems involved in expressing emotion actions such as facial expressions. As ASC are also characterised by motor deficits and atypical brain structure and function in these regions, motor structures would also be expected to show reduced activation during emotion-semantic processing. Here we used event-related fMRI to compare passive processing of emotion words in comparison to abstract verbs and animal names in typically-developing controls and individuals with ASC. Relatively reduced brain activation in ASC for emotion words, but not matched control words, was found in motor areas and cingulate cortex specifically. The degree of activation evoked by emotion words in the motor system was also associated with the extent of autistic traits as revealed by the Autism Spectrum Quotient. We suggest that hypoactivation of motor and limbic regions for emotion word processing may underlie difficulties in processing emotional language in ASC. The role that sensorimotor systems and their connections might play in the affective and social-communication difficulties in ASC is discussed. PMID:25278250

  18. 13C ENDOR Spectroscopy of Lipoxygenase-Substrate Complexes Reveals the Structural Basis for C-H Activation by Tunneling.

    Science.gov (United States)

    Horitani, Masaki; Offenbacher, Adam R; Carr, Cody A Marcus; Yu, Tao; Hoeke, Veronika; Cutsail, George E; Hammes-Schiffer, Sharon; Klinman, Judith P; Hoffman, Brian M

    2017-02-08

    In enzymatic C-H activation by hydrogen tunneling, reduced barrier width is important for efficient hydrogen wave function overlap during catalysis. For native enzymes displaying nonadiabatic tunneling, the dominant reactive hydrogen donor-acceptor distance (DAD) is typically ca. 2.7 Å, considerably shorter than normal van der Waals distances. Without a ground state substrate-bound structure for the prototypical nonadiabatic tunneling system, soybean lipoxygenase (SLO), it has remained unclear whether the requisite close tunneling distance occurs through an unusual ground state active site arrangement or by thermally sampling conformational substates. Herein, we introduce Mn 2+ as a spin-probe surrogate for the SLO Fe ion; X-ray diffraction shows Mn-SLO is structurally faithful to the native enzyme. 13 C ENDOR then reveals the locations of 13 C10 and reactive 13 C11 of linoleic acid relative to the metal; 1 H ENDOR and molecular dynamics simulations of the fully solvated SLO model using ENDOR-derived restraints give additional metrical information. The resulting three-dimensional representation of the SLO active site ground state contains a reactive (a) conformer with hydrogen DAD of ∼3.1 Å, approximately van der Waals contact, plus an inactive (b) conformer with even longer DAD, establishing that stochastic conformational sampling is required to achieve reactive tunneling geometries. Tunneling-impaired SLO variants show increased DADs and variations in substrate positioning and rigidity, confirming previous kinetic and theoretical predictions of such behavior. Overall, this investigation highlights the (i) predictive power of nonadiabatic quantum treatments of proton-coupled electron transfer in SLO and (ii) sensitivity of ENDOR probes to test, detect, and corroborate kinetically predicted trends in active site reactivity and to reveal unexpected features of active site architecture.

  19. Brain catalase activity inhibition as well as opioid receptor antagonism increases ethanol-induced HPA axis activation.

    Science.gov (United States)

    Pastor, Raúl; Sanchis-Segura, Carles; Aragon, Carlos M G

    2004-12-01

    Growing evidence indicates that brain catalase activity is involved in the psychopharmacological actions of ethanol. Recent data suggest that participation of this enzymatic system in some ethanol effects could be mediated by the endogenous opioid system. The present study assessed whether brain catalase has a role in ethanol-induced activation of the HPA axis, a neuroendocrine system modulated by the endogenous opioid neurotransmission. Swiss male mice received an intraperitoneal injection of the catalase inhibitor 3-amino-1,2,4-triazole (AT; 0-1 g/kg), and 0 to 20 hr after this administration, animals received an ethanol (0-4 g/kg; intraperitoneally) challenge. Thirty, 60, or 120 min after ethanol administration, plasma corticosterone levels were determined immunoenzymatically. In addition, we tested the effects of 45 mg/kg of cyanamide (another catalase inhibitor) and 0 to 2 mg/kg of naltrexone (nonselective opioid receptor antagonist) on ethanol-induced enhancement in plasma corticosterone values. The present study revealed that AT boosts ethanol-induced increase in plasma corticosterone levels in a dose- and time-dependent manner. However, it did not affect corticosterone values when measured after administration of saline, cocaine (4 mg/kg, intraperitoneally), or morphine (30 mg/kg, intraperitoneally). The catalase inhibitor cyanamide (45 mg/kg, intraperitoneally) also increased ethanol-related plasma corticosterone levels. These effects of AT and cyanamide on ethanol-induced corticosterone values were observed under treatment conditions that decreased significantly brain catalase activity. Indeed, a significant correlation between effects of catalase manipulations on both variables was found. Finally, we found that the administration of naltrexone enhanced the levels of plasma corticosterone after the administration of saline or ethanol. This study shows that the inhibition of brain catalase increases ethanol-induced plasma corticosterone levels. Results are

  20. A chimeric prokaryotic pentameric ligand–gated channel reveals distinct pathways of activation

    Science.gov (United States)

    Schmandt, Nicolaus; Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.; Stein, Richard A.; Bonner, Ross; Talley, Lauren; Parker, Mark D.; Mchaourab, Hassane S.; Yee, Vivien C.; Lodowski, David T.

    2015-01-01

    Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primary amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators. PMID:26415570

  1. Activity in human visual and parietal cortex reveals object-based attention in working memory.

    Science.gov (United States)

    Peters, Benjamin; Kaiser, Jochen; Rahm, Benjamin; Bledowski, Christoph

    2015-02-25

    Visual attention enables observers to select behaviorally relevant information based on spatial locations, features, or objects. Attentional selection is not limited to physically present visual information, but can also operate on internal representations maintained in working memory (WM) in service of higher-order cognition. However, only little is known about whether attention to WM contents follows the same principles as attention to sensory stimuli. To address this question, we investigated in humans whether the typically observed effects of object-based attention in perception are also evident for object-based attentional selection of internal object representations in WM. In full accordance with effects in visual perception, the key behavioral and neuronal characteristics of object-based attention were observed in WM. Specifically, we found that reaction times were shorter when shifting attention to memory positions located on the currently attended object compared with equidistant positions on a different object. Furthermore, functional magnetic resonance imaging and multivariate pattern analysis of visuotopic activity in visual (areas V1-V4) and parietal cortex revealed that directing attention to one position of an object held in WM also enhanced brain activation for other positions on the same object, suggesting that attentional selection in WM activates the entire object. This study demonstrated that all characteristic features of object-based attention are present in WM and thus follows the same principles as in perception. Copyright © 2015 the authors 0270-6474/15/353360-10$15.00/0.

  2. Stepwise multiphoton activation fluorescence reveals a new method of melanin detection

    Science.gov (United States)

    Lai, Zhenhua; Kerimo, Josef; Mega, Yair; DiMarzio, Charles A.

    2013-06-01

    The stepwise multiphoton activated fluorescence (SMPAF) of melanin, activated by a continuous-wave mode near infrared (NIR) laser, reveals a broad spectrum extending from the visible spectra to the NIR and has potential application for a low-cost, reliable method of detecting melanin. SMPAF images of melanin in mouse hair and skin are compared with conventional multiphoton fluorescence microscopy and confocal reflectance microscopy (CRM). By combining CRM with SMPAF, we can locate melanin reliably. However, we have the added benefit of eliminating background interference from other components inside mouse hair and skin. The melanin SMPAF signal from the mouse hair is a mixture of a two-photon process and a third-order process. The melanin SMPAF emission spectrum is activated by a 1505.9-nm laser light, and the resulting spectrum has a peak at 960 nm. The discovery of the emission peak may lead to a more energy-efficient method of background-free melanin detection with less photo-bleaching.

  3. Angiogenesis interactome and time course microarray data reveal the distinct activation patterns in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Liang-Hui Chu

    Full Text Available Angiogenesis involves stimulation of endothelial cells (EC by various cytokines and growth factors, but the signaling mechanisms are not completely understood. Combining dynamic gene expression time-course data for stimulated EC with protein-protein interactions associated with angiogenesis (the "angiome" could reveal how different stimuli result in different patterns of network activation and could implicate signaling intermediates as points for control or intervention. We constructed the protein-protein interaction networks of positive and negative regulation of angiogenesis comprising 367 and 245 proteins, respectively. We used five published gene expression datasets derived from in vitro assays using different types of blood endothelial cells stimulated by VEGFA (vascular endothelial growth factor A. We used the Short Time-series Expression Miner (STEM to identify significant temporal gene expression profiles. The statistically significant patterns between 2D fibronectin and 3D type I collagen substrates for telomerase-immortalized EC (TIME show that different substrates could influence the temporal gene activation patterns in the same cell line. We investigated the different activation patterns among 18 transmembrane tyrosine kinase receptors, and experimentally measured the protein level of the tyrosine-kinase receptors VEGFR1, VEGFR2 and VEGFR3 in human umbilical vein EC (HUVEC and human microvascular EC (MEC. The results show that VEGFR1-VEGFR2 levels are more closely coupled than VEGFR1-VEGFR3 or VEGFR2-VEGFR3 in HUVEC and MEC. This computational methodology can be extended to investigate other molecules or biological processes such as cell cycle.

  4. Breast fibroadenoma with increased activity on 68Ga-DOTATATE PET/CT

    Science.gov (United States)

    Papadakis, Georgios Z.; Millo, Corina; Sadowski, Samira M.; Karantanas, Apostolos H.; Bagci, Ulas; Patronas, Nicholas J.

    2016-01-01

    Fibroadenoma is the most common benign breast tumor in women of reproductive age, carrying little to no risk of breast cancer development. We report on a case of a woman with history of neuroendocrine tumor (NET), who on follow-up imaging tests underwent whole-body PET/CT study using 68Ga-DOTATATE. The scan showed increased focal activity in the right breast, which was biopsied revealing a fibroadenoma. The presented data suggests cell surface over-expression of somatostatin receptors (SSTRs) by this benign breast tumor. Moreover, this finding emphasizes the need for cautious interpretation of 68Ga-DOTATATE avid breast lesions which could mimic malignancy in NET patients. PMID:27879489

  5. Assessment of synergistic antibacterial activity of combined biosurfactants revealed by bacterial cell envelop damage.

    Science.gov (United States)

    Sana, Santanu; Datta, Sriparna; Biswas, Dipa; Sengupta, Dipanjan

    2018-02-01

    Besides potential surface activity and some beneficial physical properties, biosurfactants express antibacterial activity. Bacterial cell membrane disrupting ability of rhamnolipid produced by Pseudomonas aeruginosa C2 and a lipopeptide type biosurfactant, BS15 produced by Bacillus stratosphericus A15 was examined against Staphylococcus aureus ATCC 25923 and Escherichia coli K8813. Broth dilution technique was followed to examine minimum inhibitory concentration (MIC) of both the biosurfactants. The combined effect of rhamnolipid and BS15 against S. aureus and E. coli showed synergistic activity by expressing fractional inhibitory concentration (FIC) index of 0.43 and 0.5. Survival curve of both the bacteria showed bactericidal activity after treating with biosurfactants at their MIC obtained from FIC index study as it killed >90% of initial population. The lesser value of MIC than minimum bactericidal concentration (MBC) of the biosurfactants also supported their bactericidal activity against both the bacteria. Membrane permeability against both the bacteria was supported by amplifying protein release, increasing of cell surface hydrophobicity, withholding capacity of crystal violet dye and leakage of intracellular materials. Finally cell membrane disruption was confirmed by scanning electron microscopy (SEM). All these experiments expressed synergism and effective bactericidal activity of the combination of rhamnolipid and BS15 by enhancing the bacterial cell membrane permeability. Such effect of the combination of rhamnolipid and BS15 could make them promising alternatives to traditional antibiotic in near future. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Zebrafish Embryonic Lipidomic Analysis Reveals that the Yolk Cell Is Metabolically Active in Processing Lipid

    Directory of Open Access Journals (Sweden)

    Daniel Fraher

    2016-02-01

    Full Text Available The role of lipids in providing energy and structural cellular components during vertebrate development is poorly understood. To elucidate these roles further, we visualized lipid deposition and examined expression of key lipid-regulating genes during zebrafish embryogenesis. We also conducted a semiquantitative analysis of lipidomic composition using liquid chromatography (LC-mass spectrometry. Finally, we analyzed processing of boron-dipyrromethene (BODIPY lipid analogs injected into the yolk using thin layer chromatography. Our data reveal that the most abundant lipids in the embryo are cholesterol, phosphatidylcholine, and triglyceride. Moreover, we demonstrate that lipids are processed within the yolk prior to mobilization to the embryonic body. Our data identify a metabolically active yolk and body resulting in a dynamic lipid composition. This provides a foundation for studying lipid biology during normal or pharmacologically compromised embryogenesis.

  7. Distribution patterns of firearm discharge residues as revealed by neutron activation analysis

    International Nuclear Information System (INIS)

    Pillay, K.K.S.; Driscoll, D.C.; Jester, W.A.

    1975-01-01

    A systematic investigation using a variety of handguns has revealed the existence of distinguisable distribution patterns of firearm discharge residues on surfaces below the flight path of a bullet. The residues are identificable even at distances of 12 meters from the gun using nondestructive neutron activation analysis. The results of these investigations show that the distribution pattern for a gun is reproducible using similar ammunition and that there exist two distinct regions to the patterns developed between the firearm and the target-one with respect to the position of the gun and the other in the vicinity of the target. The judicious applications of these findings could be of significant value in criminal investigations. (T.G.)

  8. Integrated analysis of genetic variation and gene expression reveals novel variant for increased warfarin dose requirement in African Americans

    NARCIS (Netherlands)

    Hernandez, W.; Gamazon, E. R.; Aquino-Michaels, K.; Smithberger, E.; O'Brien, T. J.; Harralson, A. F.; Tuck, M.; Barbour, A.; Cavallari, L. H.; Perera, M. A.

    2017-01-01

    Essentials Genetic variants controlling gene regulation have not been explored in pharmacogenomics. We tested liver expression quantitative trait loci for association with warfarin dose response. A novel predictor for increased warfarin dose response in African Americans was identified. Precision

  9. Sudden increase in atmospheric concentration reveals strong coupling between shoot carbon uptake and root nutrient uptake in young walnut trees

    International Nuclear Information System (INIS)

    Delaire, M.; Sigogne, M.; Beaujard, F.; Frak, E.; Adam, B.; Le Roux, X.

    2005-01-01

    Short-term effects of a sudden increase in carbon dioxide concentration on nutrient uptake by roots during vegetative growth was studied in young walnut trees. Rates of carbon dioxide uptake and water loss by individual trees were determined by a branch bag method from three days before and six days after carbon dioxide concentration was increased. Nutrient uptake rates were measured concurrently by a hydroponic recirculating nutrient solution system. Carbon dioxide uptake rates increased greatly with increasing atmospheric carbon dioxide; nutrient uptake rates were proportional to carbon dioxide uptake rates, except for the phosphorus ion. Daily water loss rates were only slightly affected by elevated carbon dioxide. Overall, it was concluded that in the presence of non-limiting supplies of water and nutrients, root nutrient uptake and shoot carbon assimilation are strongly coupled in the short term in young walnut trees despite the important carbon and nutrient storage capacities od woody species. 45 refs., 7 figs

  10. Chemical stress induced by heliotrope (Heliotropium europaeum L.) allelochemicals and increased activity of antioxidant enzymes.

    Science.gov (United States)

    Abdulghader, Kalantar; Nojavan, Majid; Naghshbandi, Nabat

    2008-03-15

    The aims of this study were to evaluate the allelopathic potential of heliotrope on some biochemical processes of dodder. The preliminary experiments revealed that the effect of aqueous extract of leaves of heliotrope is higher than its seeds and roots. So, the aqueous extract of leaves was used in remaining experiments. Leaf extracts of 5 g powder per 100 mL H2O inhibited the germination of dodder seeds up to 95% and that of radish up to 100%. While, the aqueous extract of vine leaves which is a non-allelopathic plant did not have any inhibitory effect on these seeds. Vine leaf was used as a control to show that the inhibitory effect of heliotrope is due to an inhibitory compound but not due to the concentration. The leaf extract of heliotrope at 0.0, 0.1, 1.0, 2, 3, 4 and 5 g powder per 100 mL H2O reduced the radish seedling growth from 14 cm to about 0.5 cm and that of dodder from 7.5 cm to about 0.25 cm. The effects of heliotrope allelochemicals on some physiological and biochemical processes of radish was also Investigated. The activity of auxin oxidase increased in leaves and roots of radish. Suggesting that the reduced radish growth is due to the decreased active auxin levels in its leaves and roots. The activity of alpha-amylase was reduced, so reduction of starch degradation and lack of respiratory energy is the prime reason of germination inhibition in dodder and radish seeds. The level of soluble sugars increased. This is an indication of reduction of the activity of some respiratory enzymes and reduced consumption of these sugars. Proline levels were also increased, indicating that, the chemical stress is induced by leaf extract. Finally, the activities of GPX and CAT which are antioxidant enzymes were increased, along with increased extract concentration. These finding shows that the chemical stress induced by leaf extract produces super oxide (O2*) and H2O2, which is neutralized to H2O and O2 by these enzymes.

  11. Elevated atmospheric CO2 increases microbial growth rates and enzymes activity in soil

    Science.gov (United States)

    Blagodatskaya, Evgenia; Blagodatsky, Sergey; Dorodnikov, Maxim; Kuzyakov, Yakov

    2010-05-01

    Increasing the belowground translocation of assimilated carbon by plants grown under elevated CO2 can cause a shift in the structure and activity of the microbial community responsible for the turnover of organic matter in soil. We investigated the long-term effect of elevated CO2 in the atmosphere on microbial biomass and specific growth rates in root-free and rhizosphere soil. The experiments were conducted under two free air carbon dioxide enrichment (FACE) systems: in Hohenheim and Braunschweig, as well as in the intensively managed forest mesocosm of the Biosphere 2 Laboratory (B2L) in Oracle, AZ. Specific microbial growth rates (μ) were determined using the substrate-induced respiration response after glucose and/or yeast extract addition to the soil. We evaluated the effect of elevated CO2 on b-glucosidase, chitinase, phosphatase, and sulfatase to estimate the potential enzyme activity after soil amendment with glucose and nutrients. For B2L and both FACE systems, up to 58% higher μ were observed under elevated vs. ambient CO2, depending on site, plant species and N fertilization. The μ-values increased linearly with atmospheric CO2 concentration at all three sites. The effect of elevated CO2 on rhizosphere microorganisms was plant dependent and increased for: Brassica napus=Triticum aestivumyeast extract then for those growing on glucose, i.e. the effect of elevated CO2 was smoothed on rich vs. simple substrate. So, the r/K strategies ratio can be better revealed by studying growth on simple (glucose) than on rich substrate mixtures (yeast extract). After adding glucose, enzyme activities under elevated CO2 were 1.2-1.9-fold higher than under ambient CO2. This indicates the increased activity of microorganisms, which leads to accelerated C turnover in soil under elevated CO2. Our results clearly showed that the functional characteristics of the soil microbial community (i.e. specific growth rates and enzymes activity) rather than total microbial biomass

  12. The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a novel redox switch that regulates its activities

    Energy Technology Data Exchange (ETDEWEB)

    Chitnumsub, Penchit; Ittarat, Wanwipa; Jaruwat, Aritsara; Noytanom, Krittikar [National Center for Genetic Engineering and Biotechnology, 113 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani 12120 (Thailand); Amornwatcharapong, Watcharee [Mahidol University, Bangkok (Thailand); Pornthanakasem, Wichai [National Center for Genetic Engineering and Biotechnology, 113 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani 12120 (Thailand); Chaiyen, Pimchai [Mahidol University, Bangkok (Thailand); Yuthavong, Yongyuth; Leartsakulpanich, Ubolsree [National Center for Genetic Engineering and Biotechnology, 113 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani 12120 (Thailand)

    2014-06-01

    The crystal structure of P. falciparum SHMT revealed snapshots of an intriguing disulfide/sulfhydryl switch controlling the functional activity. Plasmodium falciparum serine hydroxymethyltransferase (PfSHMT), an enzyme in the dTMP synthesis cycle, is an antimalarial target because inhibition of its expression or function has been shown to be lethal to the parasite. As the wild-type enzyme could not be crystallized, protein engineering of residues on the surface was carried out. The surface-engineered mutant PfSHMT-F292E was successfully crystallized and its structure was determined at 3 Å resolution. The PfSHMT-F292E structure is a good representation of PfSHMT as this variant revealed biochemical properties similar to those of the wild type. Although the overall structure of PfSHMT is similar to those of other SHMTs, unique features including the presence of two loops and a distinctive cysteine pair formed by Cys125 and Cys364 in the tetrahydrofolate (THF) substrate binding pocket were identified. These structural characteristics have never been reported in other SHMTs. Biochemical characterization and mutation analysis of these two residues confirm that they act as a disulfide/sulfhydryl switch to regulate the THF-dependent catalytic function of the enzyme. This redox switch is not present in the human enzyme, in which the cysteine pair is absent. The data reported here can be further exploited as a new strategy to specifically disrupt the activity of the parasite enzyme without interfering with the function of the human enzyme.

  13. The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a novel redox switch that regulates its activities

    International Nuclear Information System (INIS)

    Chitnumsub, Penchit; Ittarat, Wanwipa; Jaruwat, Aritsara; Noytanom, Krittikar; Amornwatcharapong, Watcharee; Pornthanakasem, Wichai; Chaiyen, Pimchai; Yuthavong, Yongyuth; Leartsakulpanich, Ubolsree

    2014-01-01

    The crystal structure of P. falciparum SHMT revealed snapshots of an intriguing disulfide/sulfhydryl switch controlling the functional activity. Plasmodium falciparum serine hydroxymethyltransferase (PfSHMT), an enzyme in the dTMP synthesis cycle, is an antimalarial target because inhibition of its expression or function has been shown to be lethal to the parasite. As the wild-type enzyme could not be crystallized, protein engineering of residues on the surface was carried out. The surface-engineered mutant PfSHMT-F292E was successfully crystallized and its structure was determined at 3 Å resolution. The PfSHMT-F292E structure is a good representation of PfSHMT as this variant revealed biochemical properties similar to those of the wild type. Although the overall structure of PfSHMT is similar to those of other SHMTs, unique features including the presence of two loops and a distinctive cysteine pair formed by Cys125 and Cys364 in the tetrahydrofolate (THF) substrate binding pocket were identified. These structural characteristics have never been reported in other SHMTs. Biochemical characterization and mutation analysis of these two residues confirm that they act as a disulfide/sulfhydryl switch to regulate the THF-dependent catalytic function of the enzyme. This redox switch is not present in the human enzyme, in which the cysteine pair is absent. The data reported here can be further exploited as a new strategy to specifically disrupt the activity of the parasite enzyme without interfering with the function of the human enzyme

  14. Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD.

    Science.gov (United States)

    Atasoy, Selen; Roseman, Leor; Kaelen, Mendel; Kringelbach, Morten L; Deco, Gustavo; Carhart-Harris, Robin L

    2017-12-15

    Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used 'connectome-harmonic decomposition', a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.

  15. Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.

    Science.gov (United States)

    Berkes, Pietro; Orbán, Gergo; Lengyel, Máté; Fiser, József

    2011-01-07

    The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.

  16. Altered spontaneous activity in anisometropic amblyopia subjects: revealed by resting-state FMRI.

    Directory of Open Access Journals (Sweden)

    Xiaoming Lin

    Full Text Available Amblyopia, also known as lazy eye, usually occurs during early childhood and results in poor or blurred vision. Recent neuroimaging studies have found cortical structural/functional abnormalities in amblyopia. However, until now, it was still not known whether the spontaneous activity of the brain changes in amblyopia subjects. In the present study, regional homogeneity (ReHo, a measure of the homogeneity of functional magnetic resonance imaging signals, was used for the first time to investigate changes in resting-state local spontaneous brain activity in individuals with anisometropic amblyopia. Compared with age- and gender-matched subjects with normal vision, the anisometropic amblyopia subjects showed decreased ReHo of spontaneous brain activity in the right precuneus, the left medial prefrontal cortex, the left inferior frontal gyrus, and the left cerebellum, and increased ReHo of spontaneous brain activity was found in the bilateral conjunction area of the postcentral and precentral gyri, the left paracentral lobule, the left superior temporal gyrus, the left fusiform gyrus, the conjunction area of the right insula, putamen and the right middle occipital gyrus. The observed decreases in ReHo may reflect decreased visuo-motor processing ability, and the increases in ReHo in the somatosensory cortices, the motor areas and the auditory area may indicate compensatory plasticity in amblyopia.

  17. Enhanced Botrytis cinerea resistance of Arabidopsis plants grown in compost may be explained by increased expression of defense-related genes, as revealed by microarray analysis.

    Directory of Open Access Journals (Sweden)

    Guillem Segarra

    Full Text Available Composts are the products obtained after the aerobic degradation of different types of organic matter waste and can be used as substrates or substrate/soil amendments for plant cultivation. There is a small but increasing number of reports that suggest that foliar diseases may be reduced when using compost, rather than standard substrates, as growing medium. The purpose of this study was to examine the gene expression alteration produced by the compost to gain knowledge of the mechanisms involved in compost-induced systemic resistance. A compost from olive marc and olive tree leaves was able to induce resistance against Botrytis cinerea in Arabidopsis, unlike the standard substrate, perlite. Microarray analyses revealed that 178 genes were differently expressed, with a fold change cut-off of 1, of which 155 were up-regulated and 23 were down-regulated in compost-grown, as against perlite-grown plants. A functional enrichment study of up-regulated genes revealed that 38 Gene Ontology terms were significantly enriched. Response to stress, biotic stimulus, other organism, bacterium, fungus, chemical and abiotic stimulus, SA and ABA stimulus, oxidative stress, water, temperature and cold were significantly enriched, as were immune and defense responses, systemic acquired resistance, secondary metabolic process and oxireductase activity. Interestingly, PR1 expression, which was equally enhanced by growing the plants in compost and by B. cinerea inoculation, was further boosted in compost-grown pathogen-inoculated plants. Compost triggered a plant response that shares similarities with both systemic acquired resistance and ABA-dependent/independent abiotic stress responses.

  18. Increasing Physical Activity in Older Adults: Walking by Prescription in Primary Care

    Directory of Open Access Journals (Sweden)

    Vera Paisana Morais

    2017-08-01

    Full Text Available AimThe present study (PTDC/SAU-SAP/110799/2009 funded by the Portuguese Government (Fundação para a Ciência e Tecnologia – FCT aimed to test the effectiveness of a behaviour based intervention combined with a cognitive based one, designed to increase physical activity levels in older adults at Primary Health Care Centres.MethodA total of 108 participants aged over 65 years participated in the study. Participants were referred by their General Practitioner (GP and randomized by gender and marital status at the moment they started the program (single vs. couple, and allocated into one of three conditions: goal intention, action planning, action planning and coping planning. All participants received a pedometer and a logbook and were asked to register their daily number of steps for a period of 24 weeks. Study follows a longitudinal design with five assessments over a 6-month after baseline.ResultsThe test between subjects’ effects revealed an interaction between condition and participating in the study as single vs. couple. Older adults participating as singles walked more steps on average in the condition goal intention plus action planning and coping planning, whereas participants that entered in the study with their spouse, goal intention without any other planning intervention was the most effective intervention.ConclusionThe 24-week physical activity program based on the recent developments of behavioural-cognitive framework, has proven useful increasing older adults daily walking behaviour.

  19. Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

    Science.gov (United States)

    LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

    2016-02-01

    The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

  20. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

    2015-12-25

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Museum specimen data reveal emergence of a plant disease may be linked to increases in the insect vector population.

    Science.gov (United States)

    Zeilinger, Adam R; Rapacciuolo, Giovanni; Turek, Daniel; Oboyski, Peter T; Almeida, Rodrigo P P; Roderick, George K

    2017-09-01

    The emergence rate of new plant diseases is increasing due to novel introductions, climate change, and changes in vector populations, posing risks to agricultural sustainability. Assessing and managing future disease risks depends on understanding the causes of contemporary and historical emergence events. Since the mid-1990s, potato growers in the western United States, Mexico, and Central America have experienced severe yield loss from Zebra Chip disease and have responded by increasing insecticide use to suppress populations of the insect vector, the potato psyllid, Bactericera cockerelli (Hemiptera: Triozidae). Despite the severe nature of Zebra Chip outbreaks, the causes of emergence remain unknown. We tested the hypotheses that (1) B. cockerelli occupancy has increased over the last century in California and (2) such increases are related to climate change, specifically warmer winters. We compiled a data set of 87,000 museum specimen occurrence records across the order Hemiptera collected between 1900 and 2014. We then analyzed changes in B. cockerelli distribution using a hierarchical occupancy model using changes in background species lists to correct for collecting effort. We found evidence that B. cockerelli occupancy has increased over the last century. However, these changes appear to be unrelated to climate changes, at least at the scale of our analysis. To the extent that species occupancy is related to abundance, our analysis provides the first quantitative support for the hypothesis that B. cockerelli population abundance has increased, but further work is needed to link B. cockerelli population dynamics to Zebra Chip epidemics. Finally, we demonstrate how this historical macro-ecological approach provides a general framework for comparative risk assessment of future pest and insect vector outbreaks. © 2017 by the Ecological Society of America.

  2. VLA Observations Of T CrB Reveal Increase in Radio Flux Density Between 2014 and 2016

    Science.gov (United States)

    Linford, J.; Weston, J.; Chomiuk, L.; Sokoloski, J.; Nelson, T.; Mukai, K.; Finzell, T.; Rupen, M.; Mioduszewski, A.

    2016-06-01

    We report new observations of the symbiotic binary and known recurrent nova T Coronae Borealis (T CrB) with the Karl G. Janksy Very Large Array (VLA). We recently began monitoring T CrB in 2016 May after reports that it was in a super-active state at other wavelengths (Munari, Dallaporta, & Cherini 2016, NewA, 47, 7; ATEL #8675; AAVSO Special Notice 415).

  3. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

    2015-01-01

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

  4. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun, E-mail: lijunzhou@tju.edu.cn

    2015-12-25

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

  5. Using an alternate reality game to increase physical activity and decrease obesity risk of college students.

    Science.gov (United States)

    Johnston, Jeanne D; Massey, Anne P; Marker-Hoffman, Rickie Lee

    2012-07-01

    This quasi-experimental study investigated a game intervention--specifically, an alternate reality game (ARG)--as a means to influence college students' physical activity (PA). An ARG is an interactive narrative that takes place in the real world and uses multiple media to reveal a story. Three sections of a college health course (n = 115 freshman students) were assigned either to a game group that played the ARG or to a comparison group that learned how to use exercise equipment in weekly laboratory sessions. Pre- and post-intervention measures included weight, waist circumference, body mass index (BMI), percentage body fat (PBF), and self-reported moderate physical activity (MPA) and vigorous physical activity (VPA), and PA (steps/week). A significant group x time interaction (p = .001) was detected for PA, with a significant increase in PA for the game (p students--collaborative and social, experiential and media-rich. Our results provide preliminary evidence that a game intervention can positively influence PA within the college student population. © 2012 Diabetes Technology Society.

  6. Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer.

    Science.gov (United States)

    Arsova-Sarafinovska, Zorica; Eken, Ayse; Matevska, Nadica; Erdem, Onur; Sayal, Ahmet; Savaser, Ayhan; Banev, Saso; Petrovski, Daniel; Dzikova, Sonja; Georgiev, Vladimir; Sikole, Aleksandar; Ozgök, Yaşar; Suturkova, Ljubica; Dimovski, Aleksandar J; Aydin, Ahmet

    2009-08-01

    The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO(2)(-)/NO(3)(-)), cGMP and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO(2)(-)/NO(3)(-) and cGMP levels versus controls and BPH groups in both studied samples. This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

  7. Meta-analysis of Gene Expression in the Mouse Liver Reveals Biomarkers Associated with Inflammation Increased Early During Aging

    Science.gov (United States)

    Aging is associated with a predictable loss of cellular homeostasis, a decline in physiological function and an increase in various diseases. We hypothesized that similar age-related gene expression profiles would be observed in mice across independent studies. Employing a metaan...

  8. 30 years of data reveal dramatic increase in abundance of brown trout following the removal of a small hydrodam

    DEFF Research Database (Denmark)

    Birnie-Gauvin, Kim; Larsen, Martin Hage; Nielsen, Jan

    2017-01-01

    and spawning of fish. In the present study, we present thirty years of data from electrofishing surveys obtained at two sites, both prior to and following the removal of a small-scale hydropower dam in Central Jutland, Denmark. We demonstrate that the dam removal has led to a dramatic increase in trout density...

  9. Dobutamine cardiac "stress" test reveals increased arrhythmia risk in conscious rats after a single exposure to acrolein

    Science.gov (United States)

    Mild-to-moderate exercise is often used to stress the cardiovascular (CV) system of patients while monitoring them for electrocardiogram (ECG) abnormalities that may indicate underlying CV disease. We previously demonstrated that dobutamine, which increases heart rate (HR) and co...

  10. Activation of auditory white matter tracts as revealed by functional magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tae, Woo Suk [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Yakunina, Natalia; Nam, Eui-Cheol [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Kangwon National University, Department of Otolaryngology, School of Medicine, Chuncheon, Kangwon-do (Korea, Republic of); Kim, Tae Su [Kangwon National University Hospital, Department of Otolaryngology, Chuncheon (Korea, Republic of); Kim, Sam Soo [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Kangwon National University, Department of Radiology, School of Medicine, Chuncheon (Korea, Republic of)

    2014-07-15

    The ability of functional magnetic resonance imaging (fMRI) to detect activation in brain white matter (WM) is controversial. In particular, studies on the functional activation of WM tracts in the central auditory system are scarce. We utilized fMRI to assess and characterize the entire auditory WM pathway under robust experimental conditions involving the acquisition of a large number of functional volumes, the application of broadband auditory stimuli of high intensity, and the use of sparse temporal sampling to avoid scanner noise effects and increase signal-to-noise ratio. Nineteen healthy volunteers were subjected to broadband white noise in a block paradigm; each run had four sound-on/off alternations and was repeated nine times for each subject. Sparse sampling (TR = 8 s) was used. In addition to traditional gray matter (GM) auditory center activation, WM activation was detected in the isthmus and midbody of the corpus callosum (CC), tapetum, auditory radiation, lateral lemniscus, and decussation of the superior cerebellar peduncles. At the individual level, 13 of 19 subjects (68 %) had CC activation. Callosal WM exhibited a temporal delay of approximately 8 s in response to the stimulation compared with GM. These findings suggest that direct evaluation of the entire functional network of the central auditory system may be possible using fMRI, which may aid in understanding the neurophysiological basis of the central auditory system and in developing treatment strategies for various central auditory disorders. (orig.)

  11. Activation of auditory white matter tracts as revealed by functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Tae, Woo Suk; Yakunina, Natalia; Nam, Eui-Cheol; Kim, Tae Su; Kim, Sam Soo

    2014-01-01

    The ability of functional magnetic resonance imaging (fMRI) to detect activation in brain white matter (WM) is controversial. In particular, studies on the functional activation of WM tracts in the central auditory system are scarce. We utilized fMRI to assess and characterize the entire auditory WM pathway under robust experimental conditions involving the acquisition of a large number of functional volumes, the application of broadband auditory stimuli of high intensity, and the use of sparse temporal sampling to avoid scanner noise effects and increase signal-to-noise ratio. Nineteen healthy volunteers were subjected to broadband white noise in a block paradigm; each run had four sound-on/off alternations and was repeated nine times for each subject. Sparse sampling (TR = 8 s) was used. In addition to traditional gray matter (GM) auditory center activation, WM activation was detected in the isthmus and midbody of the corpus callosum (CC), tapetum, auditory radiation, lateral lemniscus, and decussation of the superior cerebellar peduncles. At the individual level, 13 of 19 subjects (68 %) had CC activation. Callosal WM exhibited a temporal delay of approximately 8 s in response to the stimulation compared with GM. These findings suggest that direct evaluation of the entire functional network of the central auditory system may be possible using fMRI, which may aid in understanding the neurophysiological basis of the central auditory system and in developing treatment strategies for various central auditory disorders. (orig.)

  12. Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

    Science.gov (United States)

    Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

    2013-01-01

    Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

  13. Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation.

    Science.gov (United States)

    Paulk, Angelique C; Zhou, Yanqiong; Stratton, Peter; Liu, Li; van Swinderen, Bruno

    2013-10-01

    Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel "whole brain" readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior.

  14. Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation.

    Science.gov (United States)

    Reyes-Reyes, E Merit; Šalipur, Francesca R; Shams, Mitra; Forsthoefel, Matthew K; Bates, Paula J

    2015-08-01

    AS1411 is a G-rich quadruplex-forming oligodeoxynucleotide that binds specifically to nucleolin, a protein found on the surface and in the cytoplasm of most malignant cells but absent from the surface/cytoplasm of most normal cells. AS1411 has shown promising clinical activity and is being widely used as a tumor-targeting agent, but its mechanism of action is not fully understood. Previously, we showed that AS1411 is taken up in cancer cells by macropinocytosis (fluid phase endocytosis) and subsequently stimulates further macropinocytosis by a nucleolin-dependent mechanism. In the current study, we have investigated the significance and molecular mechanisms of AS1411-induced macropinocytosis. Our results indicate that the antiproliferative activity of AS1411 in various cell lines correlated with its capacity to stimulate macropinocytosis. In DU145 prostate cancer cells, AS1411 induced activation of EGFR, Akt, p38, and Rac1. Activation of Akt and p38 were not critical for AS1411 activity because Akt activation was not observed in all AS1411-responsive cell lines and knockdown of p38 had no effect on AS1411's ability to inhibit proliferation. On the other hand, activation of EGFR and Rac1 appeared to play a role in AS1411 activity in all cancer cell lines examined (DU145, MDA-MB-468, A549, LNCaP) and their inhibition significantly reduced AS1411-mediated macropinocytosis and AS1411 antiproliferative activity. Interestingly, downregulation of nucleolin expression by siRNA also produced a substantial increase in activated Rac1, revealing a previously unknown role for nucleolin as a negative regulator of Rac1 activation. Our results are consistent with a model whereby AS1411 binding to nucleolin leads to sustained activation of Rac1 and causes methuosis, a novel type of nonapoptotic cell death characterized by hyperstimulation of macropinocytosis. We speculate that methuosis is a tumor/metastasis suppressor mechanism that opposes the malignant functions of Rac1 and that

  15. Natural high pCO2 increases autotrophy in Anemonia viridis (Anthozoa) as revealed from stable isotope (C, N) analysis

    OpenAIRE

    Horwitz, Rael; Borell, Esther M.; Yam, Ruth; Shemesh, Aldo; Fine, Maoz

    2015-01-01

    Contemporary cnidarian-algae symbioses are challenged by increasing CO2 concentrations (ocean warming and acidification) affecting organisms' biological performance. We examined the natural variability of carbon and nitrogen isotopes in the symbiotic sea anemone Anemonia viridis to investigate dietary shifts (autotrophy/heterotrophy) along a natural pCO2 gradient at the island of Vulcano, Italy. ?13C values for both algal symbionts (Symbiodinium) and host tissue of A. viridis became significa...

  16. Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy.

    Science.gov (United States)

    Wirsich, Jonathan; Perry, Alistair; Ridley, Ben; Proix, Timothée; Golos, Mathieu; Bénar, Christian; Ranjeva, Jean-Philippe; Bartolomei, Fabrice; Breakspear, Michael; Jirsa, Viktor; Guye, Maxime

    2016-01-01

    The in vivo structure-function relationship is key to understanding brain network reorganization due to pathologies. This relationship is likely to be particularly complex in brain network diseases such as temporal lobe epilepsy, in which disturbed large-scale systems are involved in both transient electrical events and long-lasting functional and structural impairments. Herein, we estimated this relationship by analyzing the correlation between structural connectivity and functional connectivity in terms of analytical network communication parameters. As such, we targeted the gradual topological structure-function reorganization caused by the pathology not only at the whole brain scale but also both in core and peripheral regions of the brain. We acquired diffusion (dMRI) and resting-state fMRI (rsfMRI) data in seven right-lateralized TLE (rTLE) patients and fourteen healthy controls and analyzed the structure-function relationship by using analytical network communication metrics derived from the structural connectome. In rTLE patients, we found a widespread hypercorrelated functional network. Network communication analysis revealed greater unspecific branching of the shortest path (search information) in the structural connectome and a higher global correlation between the structural and functional connectivity for the patient group. We also found evidence for a preserved structural rich-club in the patient group. In sum, global augmentation of structure-function correlation might be linked to a smaller functional repertoire in rTLE patients, while sparing the central core of the brain which may represent a pathway that facilitates the spread of seizures.

  17. Characterization of the biocontrol activity of pseudomonas fluorescens strain X reveals novel genes regulated by glucose.

    Directory of Open Access Journals (Sweden)

    Gerasimos F Kremmydas

    Full Text Available Pseudomonas fluorescens strain X, a bacterial isolate from the rhizosphere of bean seedlings, has the ability to suppress damping-off caused by the oomycete Pythium ultimum. To determine the genes controlling the biocontrol activity of strain X, transposon mutagenesis, sequencing and complementation was performed. Results indicate that, biocontrol ability of this isolate is attributed to gcd gene encoding glucose dehydrogenase, genes encoding its co-enzyme pyrroloquinoline quinone (PQQ, and two genes (sup5 and sup6 which seem to be organized in a putative operon. This operon (named supX consists of five genes, one of which encodes a non-ribosomal peptide synthase. A unique binding site for a GntR-type transcriptional factor is localized upstream of the supX putative operon. Synteny comparison of the genes in supX revealed that they are common in the genus Pseudomonas, but with a low degree of similarity. supX shows high similarity only to the mangotoxin operon of Ps. syringae pv. syringae UMAF0158. Quantitative real-time PCR analysis indicated that transcription of supX is strongly reduced in the gcd and PQQ-minus mutants of Ps. fluorescens strain X. On the contrary, transcription of supX in the wild type is enhanced by glucose and transcription levels that appear to be higher during the stationary phase. Gcd, which uses PQQ as a cofactor, catalyses the oxidation of glucose to gluconic acid, which controls the activity of the GntR family of transcriptional factors. The genes in the supX putative operon have not been implicated before in the biocontrol of plant pathogens by pseudomonads. They are involved in the biosynthesis of an antimicrobial compound by Ps. fluorescens strain X and their transcription is controlled by glucose, possibly through the activity of a GntR-type transcriptional factor binding upstream of this putative operon.

  18. Glycan structure of Gc Protein-derived Macrophage Activating Factor as revealed by mass spectrometry.

    Science.gov (United States)

    Borges, Chad R; Rehder, Douglas S

    2016-09-15

    Disagreement exists regarding the O-glycan structure attached to human vitamin D binding protein (DBP). Previously reported evidence indicated that the O-glycan of the Gc1S allele product is the linear core 1 NeuNAc-Gal-GalNAc-Thr trisaccharide. Here, glycan structural evidence is provided from glycan linkage analysis and over 30 serial glycosidase-digestion experiments which were followed by analysis of the intact protein by electrospray ionization mass spectrometry (ESI-MS). Results demonstrate that the O-glycan from the Gc1F protein is the same linear trisaccharide found on the Gc1S protein and that the hexose residue is galactose. In addition, the putative anti-cancer derivative of DBP known as Gc Protein-derived Macrophage Activating Factor (GcMAF, which is formed by the combined action of β-galactosidase and neuraminidase upon DBP) was analyzed intact by ESI-MS, revealing that the activating E. coli β-galactosidase cleaves nothing from the protein-leaving the glycan structure of active GcMAF as a Gal-GalNAc-Thr disaccharide, regardless of the order in which β-galactosidase and neuraminidase are applied. Moreover, glycosidase digestion results show that α-N-Acetylgalactosamindase (nagalase) lacks endoglycosidic function and only cleaves the DBP O-glycan once it has been trimmed down to a GalNAc-Thr monosaccharide-precluding the possibility of this enzyme removing the O-glycan trisaccharide from cancer-patient DBP in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Metagenomics, metatranscriptomics and single cell genomics reveal functional response of active Oceanospirillales to Gulf oil spill

    Energy Technology Data Exchange (ETDEWEB)

    Mason, Olivia U.; Hazen, Terry C.; Borglin, Sharon; Chain, Patrick S. G.; Dubinsky, Eric A.; Fortney, Julian L.; Han, James; Holman, Hoi-Ying N.; Hultman, Jenni; Lamendella, Regina; Mackelprang, Rachel; Malfatti, Stephanie; Tom, Lauren M.; Tringe, Susannah G.; Woyke, Tanja; Zhou, Jizhong; Rubin, Edward M.; Jansson, Janet K.

    2012-06-12

    The Deepwater Horizon oil spill in the Gulf of Mexico resulted in a deep-sea hydrocarbon plume that caused a shift in the indigenous microbial community composition with unknown ecological consequences. Early in the spill history, a bloom of uncultured, thus uncharacterized, members of the Oceanospirillales was previously detected, but their role in oil disposition was unknown. Here our aim was to determine the functional role of the Oceanospirillales and other active members of the indigenous microbial community using deep sequencing of community DNA and RNA, as well as single-cell genomics. Shotgun metagenomic and metatranscriptomic sequencing revealed that genes for motility, chemotaxis and aliphatic hydrocarbon degradation were significantly enriched and expressed in the hydrocarbon plume samples compared with uncontaminated seawater collected from plume depth. In contrast, although genes coding for degradation of more recalcitrant compounds, such as benzene, toluene, ethylbenzene, total xylenes and polycyclic aromatic hydrocarbons, were identified in the metagenomes, they were expressed at low levels, or not at all based on analysis of the metatranscriptomes. Isolation and sequencing of two Oceanospirillales single cells revealed that both cells possessed genes coding for n-alkane and cycloalkane degradation. Specifically, the near-complete pathway for cyclohexane oxidation in the Oceanospirillales single cells was elucidated and supported by both metagenome and metatranscriptome data. The draft genome also included genes for chemotaxis, motility and nutrient acquisition strategies that were also identified in the metagenomes and metatranscriptomes. These data point towards a rapid response of members of the Oceanospirillales to aliphatic hydrocarbons in the deep sea.

  20. Multitaxon activity profiling reveals differential microbial response to reduced seawater pH and oil pollution.

    Science.gov (United States)

    Coelho, Francisco J R C; Cleary, Daniel F R; Costa, Rodrigo; Ferreira, Marina; Polónia, Ana R M; Silva, Artur M S; Simões, Mário M Q; Oliveira, Vanessa; Gomes, Newton C M

    2016-09-01

    There is growing concern that predicted changes to global ocean chemistry will interact with anthropogenic pollution to significantly alter marine microbial composition and function. However, knowledge of the compounding effects of climate change stressors and anthropogenic pollution is limited. Here, we used 16S and 18S rRNA (cDNA)-based activity profiling to investigate the differential responses of selected microbial taxa to ocean acidification and oil hydrocarbon contamination under controlled laboratory conditions. Our results revealed that a lower relative abundance of sulphate-reducing bacteria (Desulfosarcina/Desulfococcus clade) due to an adverse effect of seawater acidification and oil hydrocarbon contamination (reduced pH-oil treatment) may be coupled to changes in sediment archaeal communities. In particular, we observed a pronounced compositional shift and marked reduction in the prevalence of otherwise abundant operational taxonomic units (OTUs) belonging to the archaeal Marine Benthic Group B and Marine Hydrothermal Vent Group (MHVG) in the reduced pH-oil treatment. Conversely, the abundance of several putative hydrocarbonoclastic fungal OTUs was higher in the reduced pH-oil treatment. Sediment hydrocarbon profiling, furthermore, revealed higher concentrations of several alkanes in the reduced pH-oil treatment, corroborating the functional implications of the structural changes to microbial community composition. Collectively, our results advance the understanding of the response of a complex microbial community to the interaction between reduced pH and anthropogenic pollution. In future acidified marine environments, oil hydrocarbon contamination may alter the typical mixotrophic and k-/r-strategist composition of surface sediment microbiomes towards a more heterotrophic state with lower doubling rates, thereby impairing the ability of the ecosystem to recover from acute oil contamination events. © 2016 John Wiley & Sons Ltd.

  1. Comparison of Cytotoxic Activity in Leukemic Lineages Reveals Important Features of β-Hairpin Antimicrobial Peptides.

    Science.gov (United States)

    Buri, Marcus V; Torquato, Heron F Vieira; Barros, Carlos Castilho; Ide, Jaime S; Miranda, Antonio; Paredes-Gamero, Edgar J

    2017-07-01

    Several reports described different modes of cell death triggered by antimicrobial peptides (AMPs) due to direct effects on membrane disruption, and more recently by apoptosis and necrosis-like patterns. Cytotoxic curves of four β-hairpin AMPs (gomesin, protegrin, tachyplesin, and polyphemusin) were obtained from several human leukemic lineages and normal monocytes and Two cell lines were then selected based on their cytotoxic sensitivity. One was sensitive to AMPs (K562) and the other resistant (KG-1) and their effect compared between these lineages. Thus, these lineages were chosen to further investigate biological features related with their cytotoxicities to AMPs. Stimulation with AMPs produced cell death, with activation of caspase-3, in K562 lineage. Increase on the fluidity of plasmatic membrane by reducing cholesterol potentiated cytotoxicity of AMPs in both lineages. Quantification of internal and external gomesin binding to the cellular membrane of both K562 and KG-1 cells showed that more peptide is accumulated inside of K562 cells. Additionally, evaluation of multi-drug resistant pumps activity showed that KG-1 has more activity than K562 lineage. A comparison of intrinsic gene patterns showed great differences between K562 and KG-1, but stimulation with gomesin promoted few changes in gene expression patterns. Differences in internalization process through the plasma membrane, multidrug resistance pumps activity, and gene expression pattern are important features to AMPs regulated cell death. J. Cell. Biochem. 118: 1764-1773, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Increase in platinum group elements in Mexico City as revealed from growth rings of Taxodium mucronatum ten.

    Science.gov (United States)

    Morton-Bermea, Ofelia; Beramendi-Orosco, Laura; Martínez-Reyes, Ángeles; Hernández-Álvarez, Elizabeth; González-Hernández, Galia

    2016-02-01

    Tree rings may be used as indicators of contamination events providing information on the chronology and the elemental composition of the contamination. In this framework, we report PGEs enrichment in growth rings of Taxodium mucronatum ten for trees growing in the central area of Mexico City as compared to trees growing in a non-urban environment. Concentrations of PGE were determined by ICP-MS analysis on microwave-digested tree rings. The element found in higher concentrations was Pd (1.13-87.98 μg kg(-1)), followed by Rh (0.28-36.81 μg kg(-1)) and Pt (0.106-7.21 μg kg(-1)). The concentration trends of PGEs in the tree-ring sequences from the urban area presented significant correlation values when comparing between trees (r between 0.618 and 0.98, P < 0.025) and between elements within individual trees (r between 0.76 and 0.994, P < 0.01). Furthermore, a clear increase was observed for rings after 1997, with enrichment of up to 60 times the mean concentration found for the sequence from the non-urban area and up to 40 times the mean concentration for the pre-1991 period in the urban trees. These results also demonstrate the feasibility of applying T. mucronatum ten to be used as a bioindicator of the increase in PGE in urban environments.

  3. 30 years of data reveal dramatic increase in abundance of brown trout following the removal of a small hydrodam

    DEFF Research Database (Denmark)

    Birnie-Gauvin, Kim; Larsen, Martin Hage; Nielsen, Jan

    2017-01-01

    and spawning of fish. In the present study, we present thirty years of data from electrofishing surveys obtained at two sites, both prior to and following the removal of a small-scale hydropower dam in Central Jutland, Denmark. We demonstrate that the dam removal has led to a dramatic increase in trout density......Humans and freshwater ecosystems have a long history of cohabitation. Today, nearly all major rivers of the world have an in-stream structure which changes water flow, substrate composition, vegetation, and fish assemblage composition. The realization of these effects and their subsequent impacts...... on population sustainability and conservation has led to a collective effort aimed to find ways to mitigate these impacts. Barrier removal has recently received greater interest as a potential solution to restore river connectivity, and reestablish high quality habitats, suitable for feeding, refuge...

  4. Cell-like pressure sensors reveal increase of mechanical stress towards the core of multicellular spheroids under compression.

    Science.gov (United States)

    Dolega, M E; Delarue, M; Ingremeau, F; Prost, J; Delon, A; Cappello, G

    2017-01-27

    The surrounding microenvironment limits tumour expansion, imposing a compressive stress on the tumour, but little is known how pressure propagates inside the tumour. Here we present non-destructive cell-like microsensors to locally quantify mechanical stress distribution in three-dimensional tissue. Our sensors are polyacrylamide microbeads of well-defined elasticity, size and surface coating to enable internalization within the cellular environment. By isotropically compressing multicellular spheroids (MCS), which are spherical aggregates of cells mimicking a tumour, we show that the pressure is transmitted in a non-trivial manner inside the MCS, with a pressure rise towards the core. This observed pressure profile is explained by the anisotropic arrangement of cells and our results suggest that such anisotropy alone is sufficient to explain the pressure rise inside MCS composed of a single cell type. Furthermore, such pressure distribution suggests a direct link between increased mechanical stress and previously observed lack of proliferation within the spheroids core.

  5. Increased sales and thefts of candy as a function of sales promotion activities: Preliminary findings.

    Science.gov (United States)

    Carter, N; Kindstedt, A; Melin, L

    1995-01-01

    We used an A-B-A design to evaluate the effects of two commonly used promotional activities-price reduction and increased exposure, in combination and separately-on sales and thefts of candy at a grocery store. The combination of activities and the increased exposure condition produced the greatest increases in sales. The combination of activities was also associated with the greatest increase in thefts.

  6. Proteomics analysis of dendritic cell activation by contact allergens reveals possible biomarkers regulated by Nrf2

    Energy Technology Data Exchange (ETDEWEB)

    Mussotter, Franz, E-mail: franz.mussotter@bfr.bund.de [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany); Tomm, Janina Melanie [Helmholtz Centre for Environmental Research (UFZ), Department of Molecular Systems Biology, Leipzig (Germany); El Ali, Zeina; Pallardy, Marc; Kerdine-Römer, Saadia [INSERM UMR 996, Univ Paris-Sud, Université Paris-Saclay, Chátenay-Malabry (France); Götz, Mario [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany); Bergen, Martin von [Helmholtz Centre for Environmental Research (UFZ), Department of Molecular Systems Biology, Leipzig (Germany); University of Leipzig, Institute of Biochemistry, Leipzig (Germany); Aalborg University, Department of Chemistry and Bioscience, Aalborg (Denmark); Haase, Andrea; Luch, Andreas [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany)

    2016-12-15

    Allergic contact dermatitis is a widespread disease with high clinical relevance affecting approximately 20% of the general population. Typically, contact allergens are low molecular weight electrophilic compounds which can activate the Keap1/Nrf2 pathway. We performed a proteomics study to reveal possible biomarkers for dendritic cell (DC) activation by contact allergens and to further elucidate the role of Keap1/Nrf2 signaling in this process. We used bone marrow derived dendritic cells (BMDCs) of wild-type (nrf2{sup +/+}) and Nrf2 knockout (nrf2{sup −/−}) mice and studied their response against the model contact sensitizers 2,4-dinitrochlorobenzene (DNCB), cinnamaldehyde (CA) and nickel(II) sulfate by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) in combination with electrospray ionization tandem mass spectrometry (ESI-MS/MS). Sodium dodecyl sulfate (SDS, 100 μM) served as irritant control. While treatment with nickel(II) sulfate and SDS had only little effects, CA and DNCB led to significant changes in protein expression. We found 18 and 30 protein spots up-regulated in wild-type cells treated with 50 and 100 μM CA, respectively. For 5 and 10 μM DNCB, 32 and 37 spots were up-regulated, respectively. Almost all of these proteins were not differentially expressed in nrf2{sup −/−} BMDCs, indicating an Nrf2-dependent regulation. Among them proteins were detected which are involved in oxidative stress and heat shock responses, as well as in signal transduction or basic cellular pathways. The applied approach allowed us to differentiate between Nrf2-dependent and Nrf2-independent cellular biomarkers differentially regulated upon allergen-induced DC activation. The data presented might contribute to the further development of suitable in vitro testing methods for chemical-mediated sensitization. - Highlights: • Contact allergens induce proteins involved in DC maturation Nrf2-dependently. • Induction of these proteins points to a functional

  7. ANALYSIS OF MARKETING TOOLS AND ACTIVITIES WITHIN EDUCATIONAL SERVICES ORGANIZATIONS, IN ORDER TO INCREASE THEIR EFFICIENCY

    Directory of Open Access Journals (Sweden)

    Barbu Andreea Mihaela

    2012-07-01

    Full Text Available Romanian education, which is an important pillar for human resource forming process and the basis for economic development, suffered a lot of changes in the last decades. The main factors that have influenced the undergraduate and university training programs are the political and social-cultural ones. Educational services organizations are facing various challenges as: creating and maintaining a good institutional image, managing all types of resources efficiently, motivating the academic personnel, satisfying the community needs and supporting the public policy. The marketing tools and activities help these entities to improve the educational programs and adapt them to the individual needs of the clients, to keep under control the production costs, which are limited by the small public budget and to perform and promote these services efficiently, leading to an increased organizational performance. The paper begins by presenting the current situation of higher education in Romania, underlining the fierce competition among the universities, the increased market potential and the financing sources. It continues by mentioning the advantages of strategic marketing planning for universities, as superior results and effectiveness, improved decision making and multiple benefits for the people involved. The paper reveals also the characteristics of segmenting and positioning on higher education market and the specific of marketing mix. Thereby, educational product is more easily adapted to customer needs when it is designed in collaboration with existing and future students, their parents, with other universities in the field or even with graduates. Students themselves can contribute to the increase the quality of their education. Price may be a factor of choice when future student chooses to pursue a university course, especially in those situations where the price does not include only the payment of annual fees for education. Distribution takes into

  8. Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity*

    Science.gov (United States)

    Chen, Ying; Yang, Li-Na; Cheng, Li; Tu, Shun; Guo, Shu-Juan; Le, Huang-Ying; Xiong, Qian; Mo, Ran; Li, Chong-Yang; Jeong, Jun-Seop; Jiang, Lizhi; Blackshaw, Seth; Bi, Li-Jun; Zhu, Heng; Tao, Sheng-Ce; Ge, Feng

    2013-01-01

    Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach. PMID:23824909

  9. Structural Characterization of Maize SIRK1 Kinase Domain Reveals an Unusual Architecture of the Activation Segment

    Directory of Open Access Journals (Sweden)

    Bruno Aquino

    2017-05-01

    Full Text Available Kinases are primary regulators of plant metabolism and excellent targets for plant breeding. However, most kinases, including the abundant receptor-like kinases (RLK, have no assigned role. SIRK1 is a leucine-rich repeat receptor-like kinase (LRR-RLK, the largest family of RLK. In Arabidopsis thaliana, SIRK1 (AtSIRK1 is phosphorylated after sucrose is resupplied to sucrose-starved seedlings and it modulates the sugar response by phosphorylating several substrates. In maize, the ZmSIRK1 expression is altered in response to drought stress. In neither Arabidopsis nor in maize has the function of SIRK1 been completely elucidated. As a first step toward the biochemical characterization of ZmSIRK1, we obtained its recombinant kinase domain, demonstrated that it binds AMP-PNP, a non-hydrolysable ATP-analog, and solved the structure of ZmSIRK1- AMP-PNP co-crystal. The ZmSIRK1 crystal structure revealed a unique conformation for the activation segment. In an attempt to find inhibitors for ZmSIRK1, we screened a focused small molecule library and identified six compounds that stabilized ZmSIRK1 against thermal melt. ITC analysis confirmed that three of these compounds bound to ZmSIRK1 with low micromolar affinity. Solving the 3D structure of ZmSIRK1-AMP-PNP co-crystal provided information on the molecular mechanism of ZmSIRK1 activity. Furthermore, the identification of small molecules that bind this kinase can serve as initial backbone for development of new potent and selective ZmSIRK1 antagonists.

  10. Meta-analysis reveals evolution in invasive plant species but little support for Evolution of Increased Competitive Ability (EICA).

    Science.gov (United States)

    Felker-Quinn, Emmi; Schweitzer, Jennifer A; Bailey, Joseph K

    2013-03-01

    Ecological explanations for the success and persistence of invasive species vastly outnumber evolutionary hypotheses, yet evolution is a fundamental process in the success of any species. The Evolution of Increased Competitive Ability (EICA) hypothesis (Blossey and Nötzold 1995) proposes that evolutionary change in response to release from coevolved herbivores is responsible for the success of many invasive plant species. Studies that evaluate this hypothesis have used different approaches to test whether invasive populations allocate fewer resources to defense and more to growth and competitive ability than do source populations, with mixed results. We conducted a meta-analysis of experimental tests of evolutionary change in the context of EICA. In contrast to previous reviews, there was no support across invasive species for EICA's predictions regarding defense or competitive ability, although invasive populations were more productive than conspecific native populations under noncompetitive conditions. We found broad support for genetically based changes in defense and competitive plant traits after introduction into new ranges, but not in the manner suggested by EICA. This review suggests that evolution occurs as a result of plant introduction and population expansion in invasive plant species, and may contribute to the invasiveness and persistence of some introduced species.

  11. The effect of increasing autonomy through choice on young children’s physical activity behavior

    Science.gov (United States)

    Increasing autonomy by manipulating the choice of available physical activity options in a laboratory setting can increase physical activity in older children and adults. However, the effect of manipulating the number of physically active choices has yet to be examined in young children in a gymnas...

  12. Acetylation Increases EWS-FLI1 DNA Binding and Transcriptional Activity

    International Nuclear Information System (INIS)

    Schlottmann, Silke; Erkizan, Hayriye V.; Barber-Rotenberg, Julie S.; Knights, Chad; Cheema, Amrita; Üren, Aykut; Avantaggiati, Maria L.; Toretsky, Jeffrey A.

    2012-01-01

    Ewing Sarcoma (ES) is associated with a balanced chromosomal translocation that in most cases leads to the expression of the oncogenic fusion protein and transcription factor EWS-FLI1. EWS-FLI1 has been shown to be crucial for ES cell survival and tumor growth. However, its regulation is still enigmatic. To date, no functionally significant post-translational modifications of EWS-FLI1 have been shown. Since ES are sensitive to histone deacetylase inhibitors (HDI), and these inhibitors are advancing in clinical trials, we sought to identify if EWS-FLI1 is directly acetylated. We convincingly show acetylation of the C-terminal FLI1 (FLI1-CTD) domain, which is the DNA binding domain of EWS-FLI1. In vitro acetylation studies showed that acetylated FLI1-CTD has higher DNA binding activity than the non-acetylated protein. Over-expression of PCAF or treatment with HDI increased the transcriptional activity of EWS-FLI1, when co-expressed in Cos7 cells. However, our data that evaluates the acetylation of full-length EWS-FLI1 in ES cells remains unclear, despite creating acetylation specific antibodies to four potential acetylation sites. We conclude that EWS-FLI1 may either gain access to chromatin as a result of histone acetylation or undergo regulation by direct acetylation. These data should be considered when patients are treated with HDAC inhibitors. Further investigation of this phenomenon will reveal if this potential acetylation has an impact on tumor response.

  13. Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate

    Science.gov (United States)

    Villa-Bellosta, Ricardo; Hamczyk, Magda R.; Andrés, Vicente

    2017-01-01

    Purpose Phosphorus is an essential nutrient involved in many pathobiological processes. Less than 1% of phosphorus is found in extracellular fluids as inorganic phosphate ion (Pi) in solution. High serum Pi level promotes ectopic calcification in many tissues, including blood vessels. Here, we studied the effect of elevated Pi concentration on macrophage polarization and calcification. Macrophages, present in virtually all tissues, play key roles in health and disease and display remarkable plasticity, being able to change their physiology in response to environmental cues. Methods and results High-throughput transcriptomic analysis and functional studies demonstrated that Pi induces unpolarized macrophages to adopt a phenotype closely resembling that of alternatively-activated M2 macrophages, as revealed by arginine hydrolysis and energetic and antioxidant profiles. Pi-induced macrophages showed an anti-calcifying action mediated by increased availability of extracellular ATP and pyrophosphate. Conclusion We conclude that the ability of Pi-activated macrophages to prevent calcium-phosphate deposition is a compensatory mechanism protecting tissues from hyperphosphatemia-induced pathologic calcification. PMID:28362852

  14. Beta activity in the premotor cortex is increased during stabilized as compared to normal walking

    Directory of Open Access Journals (Sweden)

    Sjoerd M. Bruijn

    2015-10-01

    Full Text Available Walking on two legs is inherently unstable. Still, we humans perform remarkable well at it, mostly without falling. To gain more understanding of the role of the brain in controlling gait stability we measured brain activity using electro-encephalography (EEG during stabilized and normal walking.Subjects walked on a treadmill in two conditions, each lasting 10 minutes; normal, and while being laterally stabilized by elastic cords. Kinematics of trunk and feet, electro-myography (EMG of neck muscles, as well as 64-channel EEG were recorded. To assess gait stability the local divergence exponent, step width, and trunk range of motion were calculated from the kinematic data. We used independent component analysis to remove movement, EMG, and eyeblink artifacts from the EEG, after which dynamic imaging of coherent sources beamformers were determined to identify cortical sources that showed a significant difference between conditions. Stabilized walking led to a significant increase in gait stability, i.e. lower local divergence exponents. Beamforming analysis of the beta band activity revealed significant sources in bilateral pre-motor cortices. Projection of sensor data on these sources showed a significant difference only in the left premotor area, with higher beta power during stabilized walking, specifically around push-off, although only significant around contralateral push-off. It appears that even during steady gait the cortex is involved in the control of stability.

  15. Ribosome•RelA structures reveal the mechanism of stringent response activation

    Science.gov (United States)

    Loveland, Anna B; Bah, Eugene; Madireddy, Rohini; Zhang, Ying; Brilot, Axel F; Grigorieff, Nikolaus; Korostelev, Andrei A

    2016-01-01

    Stringent response is a conserved bacterial stress response underlying virulence and antibiotic resistance. RelA/SpoT-homolog proteins synthesize transcriptional modulators (p)ppGpp, allowing bacteria to adapt to stress. RelA is activated during amino-acid starvation, when cognate deacyl-tRNA binds to the ribosomal A (aminoacyl-tRNA) site. We report four cryo-EM structures of E. coli RelA bound to the 70S ribosome, in the absence and presence of deacyl-tRNA accommodating in the 30S A site. The boomerang-shaped RelA with a wingspan of more than 100 Å wraps around the A/R (30S A-site/RelA-bound) tRNA. The CCA end of the A/R tRNA pins the central TGS domain against the 30S subunit, presenting the (p)ppGpp-synthetase domain near the 30S spur. The ribosome and A/R tRNA are captured in three conformations, revealing hitherto elusive states of tRNA engagement with the ribosomal decoding center. Decoding-center rearrangements are coupled with the step-wise 30S-subunit 'closure', providing insights into the dynamics of high-fidelity tRNA decoding. DOI: http://dx.doi.org/10.7554/eLife.17029.001 PMID:27434674

  16. Spatially Extensive Standardized Surveys Reveal Widespread, Multi-Decadal Increase in East Antarctic Adélie Penguin Populations.

    Science.gov (United States)

    Southwell, Colin; Emmerson, Louise; McKinlay, John; Newbery, Kym; Takahashi, Akinori; Kato, Akiko; Barbraud, Christophe; DeLord, Karine; Weimerskirch, Henri

    2015-01-01

    Seabirds are considered to be useful and practical indicators of the state of marine ecosystems because they integrate across changes in the lower trophic levels and the physical environment. Signals from this key group of species can indicate broad scale impacts or response to environmental change. Recent studies of penguin populations, the most commonly abundant Antarctic seabirds in the west Antarctic Peninsula and western Ross Sea, have demonstrated that physical changes in Antarctic marine environments have profound effects on biota at high trophic levels. Large populations of the circumpolar-breeding Adélie penguin occur in East Antarctica, but direct, standardized population data across much of this vast coastline have been more limited than in other Antarctic regions. We combine extensive new population survey data, new population estimation methods, and re-interpreted historical survey data to assess decadal-scale change in East Antarctic Adélie penguin breeding populations. We show that, in contrast to the west Antarctic Peninsula and western Ross Sea where breeding populations have decreased or shown variable trends over the last 30 years, East Antarctic regional populations have almost doubled in abundance since the 1980's and have been increasing since the earliest counts in the 1960's. The population changes are associated with five-year lagged changes in the physical environment, suggesting that the changing environment impacts primarily on the pre-breeding age classes. East Antarctic marine ecosystems have been subject to a number of changes over the last 50 years which may have influenced Adélie penguin population growth, including decadal-scale climate variation, an inferred mid-20th century sea-ice contraction, and early-to-mid 20th century exploitation of fish and whale populations.

  17. Spatially Extensive Standardized Surveys Reveal Widespread, Multi-Decadal Increase in East Antarctic Adélie Penguin Populations.

    Directory of Open Access Journals (Sweden)

    Colin Southwell

    Full Text Available Seabirds are considered to be useful and practical indicators of the state of marine ecosystems because they integrate across changes in the lower trophic levels and the physical environment. Signals from this key group of species can indicate broad scale impacts or response to environmental change. Recent studies of penguin populations, the most commonly abundant Antarctic seabirds in the west Antarctic Peninsula and western Ross Sea, have demonstrated that physical changes in Antarctic marine environments have profound effects on biota at high trophic levels. Large populations of the circumpolar-breeding Adélie penguin occur in East Antarctica, but direct, standardized population data across much of this vast coastline have been more limited than in other Antarctic regions. We combine extensive new population survey data, new population estimation methods, and re-interpreted historical survey data to assess decadal-scale change in East Antarctic Adélie penguin breeding populations. We show that, in contrast to the west Antarctic Peninsula and western Ross Sea where breeding populations have decreased or shown variable trends over the last 30 years, East Antarctic regional populations have almost doubled in abundance since the 1980's and have been increasing since the earliest counts in the 1960's. The population changes are associated with five-year lagged changes in the physical environment, suggesting that the changing environment impacts primarily on the pre-breeding age classes. East Antarctic marine ecosystems have been subject to a number of changes over the last 50 years which may have influenced Adélie penguin population growth, including decadal-scale climate variation, an inferred mid-20th century sea-ice contraction, and early-to-mid 20th century exploitation of fish and whale populations.

  18. Comparative Transcriptome Analysis of Latex Reveals Molecular Mechanisms Underlying Increased Rubber Yield in Hevea brasiliensis Self-Rooting Juvenile Clones.

    Science.gov (United States)

    Li, Hui-Liang; Guo, Dong; Zhu, Jia-Hong; Wang, Ying; Chen, Xiong-Ting; Peng, Shi-Qing

    2016-01-01

    Rubber tree (Hevea brasiliensis) self-rooting juvenile clones (JCs) are promising planting materials for rubber production. In a comparative trial between self-rooting JCs and donor clones (DCs), self-rooting JCs exhibited better performance in rubber yield. To study the molecular mechanism associated with higher rubber yield in self-rooting JCs, we sequenced and comparatively analyzed the latex of rubber tree self-rooting JCs and DCs at the transcriptome level. Total raw reads of 34,632,012 and 35,913,020 bp were obtained from the library of self-rooting JCs and DCs, respectively, by using Illumina HiSeq 2000 sequencing technology. De novo assemblies yielded 54689 unigenes from the library of self-rooting JCs and DCs. Among 54689 genes, 1716 genes were identified as differentially expressed between self-rooting JCs and DCs via comparative transcript profiling. Functional analysis showed that the genes related to the mass of categories were differentially enriched between the two clones. Several genes involved in carbohydrate metabolism, hormone metabolism and reactive oxygen species scavenging were up-regulated in self-rooting JCs, suggesting that the self-rooting JCs provide sufficient molecular basis for the increased rubber yielding, especially in the aspects of improved latex metabolisms and latex flow. Some genes encoding epigenetic modification enzymes were also differentially expressed between self-rooting JCs and DCs. Epigenetic modifications may lead to gene differential expression between self-rooting JCs and DCs. These data will provide new cues to understand the molecular mechanism underlying the improved rubber yield of H. brasiliensis self-rooting clones.

  19. Quantitative ligand and receptor binding studies reveal the mechanism of interleukin-36 (IL-36) pathway activation.

    Science.gov (United States)

    Zhou, Li; Todorovic, Viktor; Kakavas, Steve; Sielaff, Bernhard; Medina, Limary; Wang, Leyu; Sadhukhan, Ramkrishna; Stockmann, Henning; Richardson, Paul L; DiGiammarino, Enrico; Sun, Chaohong; Scott, Victoria

    2018-01-12

    IL-36 cytokines signal through the IL-36 receptor (IL-36R) and a shared subunit, IL-1RAcP (IL-1 receptor accessory protein). The activation mechanism for the IL-36 pathway is proposed to be similar to that of IL-1 in that an IL-36R agonist (IL-36α, IL-36β, or IL-36γ) forms a binary complex with IL-36R, which then recruits IL-1RAcP. Recent studies have shown that IL-36R interacts with IL-1RAcP even in the absence of an agonist. To elucidate the IL-36 activation mechanism, we considered all possible binding events for IL-36 ligands/receptors and examined these events in direct binding assays. Our results indicated that the agonists bind the IL-36R extracellular domain with micromolar affinity but do not detectably bind IL-1RAcP. Using surface plasmon resonance (SPR), we found that IL-1RAcP also does not bind IL-36R when no agonist is present. In the presence of IL-36α, however, IL-1RAcP bound IL-36R strongly. These results suggested that the main pathway to the IL-36R·IL-36α·IL-1RAcP ternary complex is through the IL-36R·IL-36α binary complex, which recruits IL-1RAcP. We could not measure the binding affinity of IL-36R to IL-1RAcP directly, so we engineered a fragment crystallizable-linked construct to induce IL-36R·IL-1RAcP heterodimerization and predicted the binding affinity during a complete thermodynamic cycle to be 74 μm The SPR analysis also indicated that the IL-36R antagonist IL-36Ra binds IL-36R with higher affinity and a much slower off rate than the IL-36R agonists, shedding light on IL-36 pathway inhibition. Our results reveal the landscape of IL-36 ligand and receptor interactions, improving our understanding of IL-36 pathway activation and inhibition. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. An Evaluation of Photographic Activity Schedules to Increase Independent Playground Skills in Young Children with Autism

    Science.gov (United States)

    Akers, Jessica S.; Higbee, Thomas S.; Pollard, Joy S.; Pellegrino, Azure J.; Gerencser, Kristina R.

    2016-01-01

    We used photographic activity schedules to increase the number of play activities completed by children with autism during unstructured time on the playground. All 3 participants engaged in more playground activities during and after training, and they continued to complete activities when novel photographs were introduced.

  1. Factor analysis of regional brain activation in bipolar and healthy individuals reveals a consistent modular structure.

    Science.gov (United States)

    Fleck, David E; Welge, Jeffrey A; Eliassen, James C; Adler, Caleb M; DelBello, Melissa P; Strakowski, Stephen M

    2018-07-01

    The neurophysiological substrates of cognition and emotion, as seen with fMRI, are generally explained using modular structures. The present study was designed to probe the modular structure of cognitive-emotional processing in bipolar and healthy individuals using factor analysis and compare the results with current conceptions of the neurophysiology of bipolar disorder. Exploratory factor analysis was used to assess patterns of covariation among brain regions-of-interest activated during the Continuous Performance Task with Emotional and Neutral Distractors in healthy and bipolar individuals without a priori constraints on the number or composition of latent factors. Results indicated a common cognitive-emotional network consisting of prefrontal, medial temporal, limbic, parietal, anterior cingulate and posterior cingulate modules. However, reduced brain activation to emotional stimuli in the frontal, medial temporal and limbic modules was apparent in the bipolar relative to the healthy group, potentially accounting for emotional dysregulation in bipolar disorder. This study is limited by a relatively small sample size recruited at a single site. The results have yet to be validated on a larger independent sample. Although the modular structure of cognitive-emotional processing is similar in bipolar and healthy individuals, activation in response to emotional/neutral cues varies. These findings are not only consistent with recent conceptions of mood regulation in bipolar disorder, but also suggest that regional activation can be considered within tighter modular structures without compromising data interpretation. This demonstration may serve as a template for data reduction in future region-of-interest analyses to increase statistical power. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. The Effect of Increasing Autonomy Through Choice on Young Children's Physical Activity Behavior.

    Science.gov (United States)

    Sanders, Gabriel J; Juvancic-Heltzel, Judith; Williamson, Megan L; Roemmich, James N; Feda, Denise M; Barkley, Jacob E

    2016-04-01

    Increasing autonomy by manipulating the choice of available physical activity options in a laboratory setting can increase physical activity in older children and adults. However, the effect of manipulating the number of physically active choices has yet to be examined in young children in a gymnasium environment. Twenty children (n = 10 girls, 6.1 ± 1.4 years old) individually participated in 2 [low choice (LC), high choice (HC)] free-choice activity conditions for 30 minutes in a 4360 square foot gymnasium. Children had access to 2 or 8 physical activity options in the LC and HC conditions, respectively. Physical activity behavior was measured via accelerometry. Children's 30-minute accelerometer counts increased (P autonomy through choice of a greater number of physically active options increased young children's physical activity participation by 20.5%.

  3. Get Active Orlando: changing the built environment to increase physical activity.

    Science.gov (United States)

    McCreedy, Malisa; Leslie, Jill G

    2009-12-01

    Active Living by Design's Get Active Orlando partnership (GAO) focused on downtown Orlando's Community Redevelopment Area, including the Parramore Heritage District, home to many low-income and ethnically diverse residents, including many seniors. The area had undergone substantial development, and GAO aimed to incorporate active living considerations into the city's changing landscape. Get Active Orlando conducted a baseline survey of all streets, sidewalks, and bicycle lanes in the project area and identified a sequence of plans and policies in which to incorporate changes identified in the assessment. To create more immediate opportunities for active living, the partnership initiated a senior walking program, a bicycle refurbishment and giveaway program, and community bicycle-riding events, and led a social-marketing campaign that emphasized simple lifestyle changes. Get Active Orlando influenced adoption of public policies supporting active living in Orlando, including the Downtown Transportation Plan, Streetscape Guidelines, Design Standards Review Checklist, and growth management policies. Establishment of the Mayor's Advisory Council on Active Living is testament to the heightened significance of active living in Orlando. Initial assessment data served as a strong platform for policy change. Creating connections across disciplines including land-use planning, transportation, public health, and economic development allowed GAO to secure substantial policy change to influence design of the built environment. Engaging community members, including youth, as leaders was an important factor in program success. The physical environment in Orlando's Community Redevelopment Area is beginning to change as a reflection of a new policy framework designed to support active living.

  4. PERCEPTION STIMULATION GROUP ACTIVITY THERAPY INCREASES E CHILDREN SELF ESTEEM AT PRISON

    Directory of Open Access Journals (Sweden)

    Ah. Yusuf

    2017-07-01

    Full Text Available Introduction: Prison is societal implementer unit which accommodate care and develop the delinquent children. It was recorded that 57% of children at Blitar Child Prison undergo some self concept problems such as low self esteem. This was caused by some factors such as society’s stigmatization toward criminals, development pattern and education, and less support from family. If the self esteem problem is not being overcome soon, the children may  fell useless, disable to control their self and recrime when they are back to society. The objective of this study was to analyze the influence of  GAT (Group Activity Therapy perception stimulation in increasing the children  self esteem at prison. Method:  A quasy experimental pre post control design was used in this study. Samples were recruited by using total sampling and there were 22 samples as on inclusion criteria. The independent variable was GAT perception stimulation and the dependent variable was increasing self esteem of these childen. Data were collected by using questionnare and analyzed by using Wilcoxon Signed Ranks Test and Mann Whitney U Test with the significance level α≤0.05.Result:  The result showed that controlled group has significance level was p=0.654, it is mean there was no self esteem change before and after GAT perception stimulation was given. Whereas treatment group has significance level was p=0.001, it revealed that  there was self esteem change before and after GAT perception stimulation was given. The result of Mann Whitney U Test showed p=0.000 which means was accepted. Discussion: It can be concluded that perception stimulation can increase the children self esteem at prison. Further studies are recommended to study the effect of GAT perception stimulation modified by skill therapy in increasing children self esteem in prison.

  5. Increased diagnostic activity in general practice during the year preceding colorectal cancer diagnosis.

    Science.gov (United States)

    Hansen, Pernille Libach; Hjertholm, Peter; Vedsted, Peter

    2015-08-01

    Accurate diagnostic activity in general practice before colorectal cancer (CRC) diagnosis is crucial for an early detection of CRC. This study aimed to investigate the rates of daytime consultations, hemoglobin (Hb) measurements and medicine prescriptions for hemorrhoids in general practice in the year preceding CRC diagnosis. Using Danish registries, we conducted a population-based matched cohort study including CRC patients aged 40-80 years (n = 19,209) and matched references (n = 192,090). We calculated odds ratios (ORs) using a conditional logistical regression model and incidence rate ratios (IRRs) using a negative binomial regression model. The CRC patients had significantly more consultations from 9 months before diagnosis and significantly increased rates of Hb measurements from up to 17 months before diagnosis compared with references. Furthermore, up to 18 months before diagnosis, CRC patients had significantly higher rates of prescriptions for hemorrhoids; and 2 months before diagnosis, the IRR was 12.24 (95% confidence interval (CI): 10.29-14.55) for men. The positive predictive value (PPV) of CRC for having a first-time prescription for hemorrhoids was highest among men aged 70-80 years [PPV = 3.2% (95% CI: 2.8-3.7)]. High prescription rates were predominantly seen among rectal cancer patients, whereas colon cancer patients had higher rates of consultations and Hb measurements. This study revealed a significant increase in healthcare seeking and diagnostic activity in general practice in the year prior to CRC diagnosis, which indicates the presence of a "diagnostic time window" and a potential for earlier diagnosis of CRC based on clinical signs and symptoms. © 2015 UICC.

  6. Trace metal depositional patterns from an open pit mining activity as revealed by archived avian gizzard contents

    Energy Technology Data Exchange (ETDEWEB)

    Bendell, L.I., E-mail: bendell@sfu.ca

    2011-02-15

    Archived samples of blue grouse (Dendragapus obscurus) gizzard contents, inclusive of grit, collected yearly between 1959 and 1970 were analyzed for cadmium, lead, zinc, and copper content. Approximately halfway through the 12-year sampling period, an open-pit copper mine began activities, then ceased operations 2 years later. Thus the archived samples provided a unique opportunity to determine if avian gizzard contents, inclusive of grit, could reveal patterns in the anthropogenic deposition of trace metals associated with mining activities. Gizzard concentrations of cadmium and copper strongly coincided with the onset of opening and the closing of the pit mining activity. Gizzard zinc and lead demonstrated significant among year variation; however, maximum concentrations did not correlate to mining activity. The archived gizzard contents did provide a useful tool for documenting trends in metal depositional patterns related to an anthropogenic activity. Further, blue grouse ingesting grit particles during the time of active mining activity would have been exposed to toxicologically significant levels of cadmium. Gizzard lead concentrations were also of toxicological significance but not related to mining activity. This type of 'pulse' toxic metal exposure as a consequence of open-pit mining activity would not necessarily have been revealed through a 'snap-shot' of soil, plant or avian tissue trace metal analysis post-mining activity. - Research Highlights: {yields} Archived gizzard samples reveals mining history. {yields} Grit ingestion exposes grouse to cadmium and lead. {yields} Grit selection includes particles enriched in cadmium. {yields} Cadmium enriched particles are of toxicological significance.

  7. Metabolic activity of uncultivated magnetotactic bacteria revealed by NanoSIMS

    Science.gov (United States)

    He, M.; Zhang, W.; Gu, L.; Pan, Y.; Lin, W.

    2017-12-01

    Microorganisms that exhibit magnetotaxis behavior, collectively known as the magnetotactic bacteria (MTB), are those whose motility is influenced by the Earth's magnetic field. MTB are a physiologically diverse group of bacteria with a unique feature of intracellular biomineralization of magnetosomes (Fe3O4 and/or Fe3S4) (Bazylinski et al., 2013). However, the ecophysiology of uncultivated MTB, especially those within the Nitrospirae phylum forming hundreds of bullet-shaped magnetite magnetosomes per cell, is still not well characterized (Lin et al., 2014). Nanoscale secondary ion mass spectrometry (NanoSIMS) is a powerful tool for revealing element distribution in nanometer-scale resolution, which opens exciting possibilities for the study of interactions between microorganisms and environments (Gao et al., 2016; Musat et al., 2016). Here we applied NanoSIMS to investigate the dynamics of carbon and nitrogen assimilations in two magnetotactic Nitrospirae populations at single cell level. Our NanoSIMS results confirmed the metabolic potential of Nitrospirae MTB proposed by genomic and metagenomic analysis and provided additional insights into the ecophysiology of uncultivated MTB. This study suggests that NanoSIMS-based analyses are powerful approaches for investigating and characterizing the ecological function of environmental microorganisms. References: Bazylinski D A., Lefèvre, C T., Schüler D., 2013. Magnetotactic Bacteria. 453-494.Lin W, Bazylinski DA, Xiao T, Wu L- F, Pan Y., 2014. Life with compass: diversity and biogeography of magnetotactic bacteria. Environ Microbiol, 16: 1462-2920.Gao D., Huang X., Tao Y., 2016. A critical review of NanoSIMS in analysis of microbial metabolic activities at single-cell level. Crit Rev Biotechnol, 36: 884-890.Musat N., Musat F., Weber PK., Pett-Ridge J., 2016. Tracking microbial interactions with NanoSIMS. Curr Opin Biotechnol, 41: 114-121.

  8. Epitope mapping for monoclonal antibody reveals the activation mechanism for αVβ3 integrin.

    Directory of Open Access Journals (Sweden)

    Tetsuji Kamata

    Full Text Available Epitopes for a panel of anti-αVβ3 monoclonal antibodies (mAbs were investigated to explore the activation mechanism of αVβ3 integrin. Experiments utilizing αV/αIIb domain-swapping chimeras revealed that among the nine mAbs tested, five recognized the ligand-binding β-propeller domain and four recognized the thigh domain, which is the upper leg of the αV chain. Interestingly, the four mAbs included function-blocking as well as non-functional mAbs, although they bound at a distance from the ligand-binding site. The epitopes for these four mAbs were further determined using human-to-mouse αV chimeras. Among the four, P3G8 recognized an amino acid residue, Ser-528, located on the side of the thigh domain, while AMF-7, M9, and P2W7 all recognized a common epitope, Ser-462, that was located close to the α-genu, where integrin makes a sharp bend in the crystal structure. Fibrinogen binding studies for cells expressing wild-type αVβ3 confirmed that AMF-7, M9, and P2W7 were inhibitory, while P3G8 was non-functional. However, these mAbs were all unable to block binding when αVβ3 was constrained in its extended conformation. These results suggest that AMF-7, M9, and P2W7 block ligand binding allosterically by stabilizing the angle of the bend in the bent conformation. Thus, a switchblade-like movement of the integrin leg is indispensable for the affinity regulation of αVβ3 integrin.

  9. Impedance spectroscopy of micro-Droplets reveals activation of Bacterial Mechanosensitive Channels in Hypotonic Solutions

    Science.gov (United States)

    Ebrahimi, Aida; Alam, Muhammad A.

    Rapid detection of bacterial pathogens is of great importance in healthcare, food safety, environmental monitoring, and homeland security. Most bacterial detection platforms rely on binary fission (i.e. cell growth) to reach a threshold cell population that can be resolved by the sensing method. Since cell division depends on the bacteria type, the detection time of such methods can vary from hours to days. In contrast, in this work, we show that bacteria cells can be detected within minutes by relying on activation of specific protein channels, i.e. mechanosensitive channels (MS channels). When cells are exposed to hypotonic solutions, MS channels allow efflux of solutes to the external solution which leads to release the excessive membrane tension. Release of the cytoplasmic solutes, in turn, results in increase of the electrical conductance measured by droplet-based impedance sensing. The approach can be an effective technique for fast, pre-screening of bacterial contamination at ultra-low concentration.

  10. Multichannel detrended fluctuation analysis reveals synchronized patterns of spontaneous spinal activity in anesthetized cats.

    Directory of Open Access Journals (Sweden)

    Erika E Rodríguez

    Full Text Available The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA to analyze the correlation dynamics of spontaneous spinal activity (SSA from time series analysis. This method together with the classical detrended fluctuation analysis (DFA were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs recorded either from one lumbar segment (DFA-α mean = 1.04[Formula: see text]0.09 or simultaneously from several lumbar segments (mDFA-α mean = 1.01[Formula: see text]0.06, where α = 0.5 indicates randomness while α = 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA-[Formula: see text] = 0.992 as compared to initial conditions mDFA-α = 1.186. The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA-α = 0

  11. Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis

    DEFF Research Database (Denmark)

    Ødum, Niels; Morling, Niels; Platz, P

    1987-01-01

    The presence of activated T cells as judged from the reaction with monoclonal antibodies (MoAb) against (a) a late stage T cell activation antigen (VLA-1), (b) the interleukin 2 (IL2) receptor (CD25), and (c) four different HLA class II molecules (HLA-DR, DRw52, DQ, and DP) was studied in 15 pati...

  12. Increasing Physical Activity during the School Day through Physical Activity Classes: Implications for Physical Educators

    Science.gov (United States)

    Adkins, Megan; Bice, Matt; Bartee, Todd; Heelan, Kate

    2015-01-01

    Across the nation schools are adopting health and wellness policies, specifically physical activity (PA) initiatives that aid healthy long-term lifestyles. Interest has been generated about the inclusion of physical activity classes to complement existing physical education classes. Furthermore, discussion has evolved as to if additional…

  13. Characterization of the active microbiotas associated with honey bees reveals healthier and broader communities when colonies are genetically diverse.

    Directory of Open Access Journals (Sweden)

    Heather R Mattila

    Full Text Available Recent losses of honey bee colonies have led to increased interest in the microbial communities that are associated with these important pollinators. A critical function that bacteria perform for their honey bee hosts, but one that is poorly understood, is the transformation of worker-collected pollen into bee bread, a nutritious food product that can be stored for long periods in colonies. We used 16S rRNA pyrosequencing to comprehensively characterize in genetically diverse and genetically uniform colonies the active bacterial communities that are found on honey bees, in their digestive tracts, and in bee bread. This method provided insights that have not been revealed by past studies into the content and benefits of honey bee-associated microbial communities. Colony microbiotas differed substantially between sampling environments and were dominated by several anaerobic bacterial genera never before associated with honey bees, but renowned for their use by humans to ferment food. Colonies with genetically diverse populations of workers, a result of the highly promiscuous mating behavior of queens, benefited from greater microbial diversity, reduced pathogen loads, and increased abundance of putatively helpful bacteria, particularly species from the potentially probiotic genus Bifidobacterium. Across all colonies, Bifidobacterium activity was negatively correlated with the activity of genera that include pathogenic microbes; this relationship suggests a possible target for understanding whether microbes provide protective benefits to honey bees. Within-colony diversity shapes microbiotas associated with honey bees in ways that may have important repercussions for colony function and health. Our findings illuminate the importance of honey bee-bacteria symbioses and examine their intersection with nutrition, pathogen load, and genetic diversity, factors that are considered key to understanding honey bee decline.

  14. Coseismic landslides reveal near-surface rock strength in a high-relief tectonically active setting

    Science.gov (United States)

    Gallen, Sean F.; Clark, Marin K.; Godt, Jonathan W.

    2014-01-01

    We present quantitative estimates of near-surface rock strength relevant to landscape evolution and landslide hazard assessment for 15 geologic map units of the Longmen Shan, China. Strength estimates are derived from a novel method that inverts earthquake peak ground acceleration models and coseismic landslide inventories to obtain material proper- ties and landslide thickness. Aggregate rock strength is determined by prescribing a friction angle of 30° and solving for effective cohesion. Effective cohesion ranges are from 70 kPa to 107 kPa for 15 geologic map units, and are approximately an order of magnitude less than typical laboratory measurements, probably because laboratory tests on hand-sized specimens do not incorporate the effects of heterogeneity and fracturing that likely control near-surface strength at the hillslope scale. We find that strength among the geologic map units studied varies by less than a factor of two. However, increased weakening of units with proximity to the range front, where precipitation and active fault density are the greatest, suggests that cli- matic and tectonic factors overwhelm lithologic differences in rock strength in this high-relief tectonically active setting.

  15. Amplitude-modulated stimuli reveal auditory-visual interactions in brain activity and brain connectivity.

    Science.gov (United States)

    Laing, Mark; Rees, Adrian; Vuong, Quoc C

    2015-01-01

    The temporal congruence between auditory and visual signals coming from the same source can be a powerful means by which the brain integrates information from different senses. To investigate how the brain uses temporal information to integrate auditory and visual information from continuous yet unfamiliar stimuli, we used amplitude-modulated tones and size-modulated shapes with which we could manipulate the temporal congruence between the sensory signals. These signals were independently modulated at a slow or a fast rate. Participants were presented with auditory-only, visual-only, or auditory-visual (AV) trials in the fMRI scanner. On AV trials, the auditory and visual signal could have the same (AV congruent) or different modulation rates (AV incongruent). Using psychophysiological interaction analyses, we found that auditory regions showed increased functional connectivity predominantly with frontal regions for AV incongruent relative to AV congruent stimuli. We further found that superior temporal regions, shown previously to integrate auditory and visual signals, showed increased connectivity with frontal and parietal regions for the same contrast. Our findings provide evidence that both activity in a network of brain regions and their connectivity are important for AV integration, and help to bridge the gap between transient and familiar AV stimuli used in previous studies.

  16. Amplitude-modulated stimuli reveal auditory-visual interactions in brain activity and brain connectivity

    Directory of Open Access Journals (Sweden)

    Mark eLaing

    2015-10-01

    Full Text Available The temporal congruence between auditory and visual signals coming from the same source can be a powerful means by which the brain integrates information from different senses. To investigate how the brain uses temporal information to integrate auditory and visual information from continuous yet unfamiliar stimuli, we use amplitude-modulated tones and size-modulated shapes with which we could manipulate the temporal congruence between the sensory signals. These signals were independently modulated at a slow or a fast rate. Participants were presented with auditory-only, visual-only or auditory-visual (AV trials in the scanner. On AV trials, the auditory and visual signal could have the same (AV congruent or different modulation rates (AV incongruent. Using psychophysiological interaction analyses, we found that auditory regions showed increased functional connectivity predominantly with frontal regions for AV incongruent relative to AV congruent stimuli. We further found that superior temporal regions, shown previously to integrate auditory and visual signals, showed increased connectivity with frontal and parietal regions for the same contrast. Our findings provide evidence that both activity in a network of brain regions and their connectivity are important for auditory-visual integration, and help to bridge the gap between transient and familiar AV stimuli used in previous studies.

  17. Structure-activity studies of RFamide peptides reveal subtype-selective activation of neuropeptide FF1 and FF2 receptors.

    Science.gov (United States)

    Findeisen, Maria; Rathmann, Daniel; Beck-Sickinger, Annette G

    2011-06-06

    Selectivity is a major issue in closely related multiligand/multireceptor systems. In this study we investigated the RFamide systems of hNPFF₁R and hNPFF₂R that bind the endogenous peptide hormones NPFF, NPAF, NPVF, and NPSF. By use of a systematic approach, we characterized the role of the C-terminal dipeptide with respect to agonistic properties using synthesized [Xaa 7]NPFF and [Xaa 8]NPFF analogues. We were able to identify only slight differences in potency upon changing the position of Arg 7, as all modifications resulted in identical behavior at the NPFF₁R and NPFF₂R. However, the C-terminal Phe 8 was able to be replaced by Trp or His with only a minor loss in potency at the NPFF₂R relative to the NPFF₁R. Analogues with shorter side chains, such as α-amino-4-guanidino butyric acid ([Agb 7]NPFF) or phenylglycine ([Phg 8]NPFF), decreased efficacy for the NPFF₁ R to 25-31 % of the maximal response, suggesting that these agonist-receptor complexes are more susceptible to structural modifications. In contrast, mutations to the conserved Asp 6.59 residue in the third extracellular loop of both receptors revealed a higher sensitivity toward the hNPFF₂R receptor than toward hNPFF₁R. These data provide new insight into the subtype-specific agonistic activation of the NPFF₁ and NPFF(2) receptors that are necessary for the development of selective agonists. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Low Dopamine D2 Receptor Increases Vulnerability to Obesity Via Reduced Physical Activity, Not Increased Appetitive Motivation.

    Science.gov (United States)

    Beeler, Jeff A; Faust, Rudolf P; Turkson, Susie; Ye, Honggang; Zhuang, Xiaoxi

    2016-06-01

    The dopamine D2 receptor (D2R) has received much attention in obesity studies. Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons. It is often suggested that reduced D2R generates a reward deficiency and altered appetitive motivation that induces compulsive eating and contributes to obesity. Although dopamine is known to regulate physical activity, it is often neglected in these studies, leaving open the question of whether reduced D2R contributes to obesity through alterations in energy expenditure and activity. We generated a D2R knockdown (KD) mouse line and assessed both energy expenditure and appetitive motivation under conditions of diet-induced obesity. The KD mice did not gain more weight or show increased appetitive motivation compared with wild-type mice in a standard environment; however, in an enriched environment with voluntary exercise opportunities, KD mice exhibited dramatically lower activity and became more obese than wild-type mice, obtaining no protective benefit from exercise opportunities. These data suggest the primary contribution of altered D2R signaling to obesity lies in altered energy expenditure rather than the induction of compulsive overeating. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. LOW DOPAMINE D2 RECEPTOR INCREASES VULNERABILITY TO OBESITY VIA REDUCED PHYSICAL ACTIVITY NOT INCREASED APPETITIVE MOTIVATION

    Science.gov (United States)

    Beeler, Jeff A.; Faust, Rudolf P.; Turkson, Susie; Ye, Honggang; Zhuang, Xiaoxi

    2015-01-01

    Background The dopamine D2 receptor (D2R) has received much attention in obesity studies. Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons. It is often suggested that reduced D2R generates a “reward deficiency” and altered appetitive motivation that induces compulsive eating and contributes to obesity. Although dopamine is known to regulate physical activity, it is often neglected in these studies, leaving open the question of whether reduced D2R contributes to obesity through alterations in energy expenditure and activity. Methods We generated a D2R knockdown (KD) mouse line and assessed both energy expenditure and appetitive motivation under conditions of diet-induced obesity. Results The KD mice did not gain more weight or show increased appetitive motivation compared to wild-type (WT) in a standard environment; however, in an enriched environment with voluntary exercise opportunities, KD mice exhibited dramatically lower activity and became more obese than WT, obtaining no protective benefit from exercise opportunities. Conclusions These data suggest the primary contribution of altered D2R signaling to obesity lies in altered energy expenditure rather than the induction of compulsive overeating. PMID:26281715

  20. Can schoolyard improvements increase physical activity for the least active students, or just provide better opportunities for the most active?

    DEFF Research Database (Denmark)

    Breum, Lars; Toftager, M.; Troelsen, J.

    2014-01-01

    at the school had equal impact on all students regardless of their PA at baseline [1]. Method The SPACE-study used a cluster randomized controlled study design with a 2-year follow-up, and enrolled 1348 students aged 11–13 years from 14 schools in Denmark. A web-based questionnaire was used to obtain knowledge...... as “the most active”. At the intervention schools the proportion of student who reported good possibilities for outdoor PA increased (71% to 75%), while the proportion decreased at the comparison schools (87% to 68%). The proportion of students reporting to be active daily during recess decreased for all...... of PA during recess and in leisure time. The multicomponent intervention comprised 11 components, and included a combination of changes to the physical environment and organizational changes. Results At baseline, 73% of the students reported to engage in sport outside school and were characterized...

  1. Decreasing Stereotypy in Preschoolers with Autism Spectrum Disorder: The Role of Increased Physical Activity and Function

    Science.gov (United States)

    McLaughlin, Constance Ann Hylton

    2010-01-01

    This study used increased physical activity during recess to reduce stereotypy in preschoolers with Autism Spectrum Disorder. Results indicate increasing physical activity can be used as an intervention to reduce automatically maintained stereotypy in preschoolers with ASD. The intervention had a lesser effect on a preschooler whose stereotypy was…

  2. Male Adolescents' Reasons for Participating in Physical Activity, Barriers to Participation, and Suggestions for Increasing Participation

    Science.gov (United States)

    Allison, Kenneth R.; Dwyer, John J. M.; Goldenberg, Ellie; Fein, Allan; Yoshida, Karen K.; Boutilier, Marie

    2005-01-01

    This study explored male adolescents' reasons for participating in moderate and vigorous physical activity, perceived barriers to moderate and vigorous physical activity, and suggestions as to what can be done to increase participation in physical activity. A total of 26 male 15- and 16-year-old adolescents participated in focus group sessions,…

  3. Texting to increase physical activity among teenagers (TXT Me!): Rationale, design, and methods proposal

    Science.gov (United States)

    Physical activity decreases from childhood through adulthood. Among youth, teenagers (teens) achieve the lowest levels of physical activity, and high school age youth are particularly at risk of inactivity. Effective methods are needed to increase youth physical activity in a way that can be maintai...

  4. Pyrosequencing Reveals Soil Enzyme Activities and Bacterial Communities Impacted by Graphene and Its Oxides.

    Science.gov (United States)

    Rong, Yan; Wang, Yi; Guan, Yina; Ma, Jiangtao; Cai, Zhiqiang; Yang, Guanghua; Zhao, Xiyue

    2017-10-25

    Graphene (GN) and graphene oxides (GOs) are novel carbon nanomaterial; they have been attracting much attention because of their excellent properties and are widely applied in many areas, including energy, electronics, biomedicine, environmental science, etc. With industrial production and consumption of GN/GO, they will inevitably enter the soil and water environments. GN/GO may directly cause certain harm to microorganisms and lead to ecological and environmental risks. GOs are GN derivatives with abundant oxygen-containing functional groups in their graphitic backbone. The structure and chemistry of GN show obvious differences compared to those of GO, which lead to the different environmental behaviors. In this study, four different types of soil (S1-S4) were employed to investigate the effect of GN and GO on soil enzymatic activity, microbial population, and bacterial community through pyrosequencing of 16S rRNA gene amplicons. The results showed that soil enzyme activity (invertase, protease, catalase, and urease) and microbial population (bacteria, actinomycetes, and fungi) changed after GN/GO release into soils. Soil microbial community species are more rich, and the diversity also increases after GO/GN application. The phylum of Proteobacteria increased at 90 days after treatment (DAT) after GN/GO application. The phylum of Chloroflexi occurred after GN application at 90 DAT in S1 soil and reached 4.6%. Proteobacteria was the most abundant phylum in S2, S3, and S4 soils; it ranged from 43.6 to 71.4% in S2 soil, from 45.6 to 73.7% in S3 soil, and from 38.1 to 56.7% in S4 soil. The most abundant genera were Bacillus (37.5-47.0%) and Lactococcus (28.0-39.0%) in S1 soil, Lysobacter and Flavobacterium in S2 soil, Pedobacter in S3 soil, and Massilia in S4 soil. The effect of GN and GO on the soil microbial community is time-dependent, and there are no significant differences between the samples at 10 and 90 DAT.

  5. Systematically Altering Bacterial SOS Activity under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics.

    Science.gov (United States)

    Mo, Charlie Y; Manning, Sara A; Roggiani, Manuela; Culyba, Matthew J; Samuels, Amanda N; Sniegowski, Paul D; Goulian, Mark; Kohli, Rahul M

    2016-01-01

    The bacterial SOS response is a DNA damage repair network that is strongly implicated in both survival and acquired drug resistance under antimicrobial stress. The two SOS regulators, LexA and RecA, have therefore emerged as potential targets for adjuvant therapies aimed at combating resistance, although many open questions remain. For example, it is not well understood whether SOS hyperactivation is a viable therapeutic approach or whether LexA or RecA is a better target. Furthermore, it is important to determine which antimicrobials could serve as the best treatment partners with SOS-targeting adjuvants. Here we derived Escherichia coli strains that have mutations in either lexA or recA genes in order to cover the full spectrum of possible SOS activity levels. We then systematically analyzed a wide range of antimicrobials by comparing the mean inhibitory concentrations (MICs) and induced mutation rates for each drug-strain combination. We first show that significant changes in MICs are largely confined to DNA-damaging antibiotics, with strains containing a constitutively repressed SOS response impacted to a greater extent than hyperactivated strains. Second, antibiotic-induced mutation rates were suppressed when SOS activity was reduced, and this trend was observed across a wider spectrum of antibiotics. Finally, perturbing either LexA or RecA proved to be equally viable strategies for targeting the SOS response. Our work provides support for multiple adjuvant strategies, while also suggesting that the combination of an SOS inhibitor with a DNA-damaging antibiotic could offer the best potential for lowering MICs and decreasing acquired drug resistance. IMPORTANCE Our antibiotic arsenal is becoming depleted, in part, because bacteria have the ability to rapidly adapt and acquire resistance to our best agents. The SOS pathway, a widely conserved DNA damage stress response in bacteria, is activated by many antibiotics and has been shown to play central role in

  6. Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Ytting, H; Jensenius, Jens Christian; Christensen, I J

    2004-01-01

    in certain patient groups. It is hypothesized that a deficient MBL pathway might be more frequent among patients with CRC than in healthy individuals. The MBL pathway was therefore evaluated in serum obtained preoperatively from 193 patients with primary CRC and in serum from 150 healthy volunteers. METHODS......: Serum MBL concentrations and MBL/MASP activity were determined using immunofluorometric assays. The levels are presented as the median, inter-quartile range and range. RESULTS: Serum MBL levels were significantly (P ..., inter-quartile range) compared with levels in healthy blood donors (924 (230-1476) ng/mL). Similarly, the MBL/MASP activity was significantly (P age, gender, tumour location...

  7. Age-related increase in brain activity during task-related and -negative networks and numerical inductive reasoning.

    Science.gov (United States)

    Sun, Li; Liang, Peipeng; Jia, Xiuqin; Qi, Zhigang; Li, Kuncheng

    2014-01-01

    Recent neuroimaging studies have shown that elderly adults exhibit increased and decreased activation on various cognitive tasks, yet little is known about age-related changes in inductive reasoning. To investigate the neural basis for the aging effect on inductive reasoning, 15 young and 15 elderly subjects performed numerical inductive reasoning while in a magnetic resonance (MR) scanner. Functional magnetic resonance imaging (fMRI) analysis revealed that numerical inductive reasoning, relative to rest, yielded multiple frontal, temporal, parietal, and some subcortical area activations for both age groups. In addition, the younger participants showed significant regions of task-induced deactivation, while no deactivation occurred in the elderly adults. Direct group comparisons showed that elderly adults exhibited greater activity in regions of task-related activation and areas showing task-induced deactivation (TID) in the younger group. Our findings suggest an age-related deficiency in neural function and resource allocation during inductive reasoning.

  8. Regional passive seismic monitoring reveals dynamic glacier activity on Spitsbergen, Svalbard

    Directory of Open Access Journals (Sweden)

    Andreas Köhler

    2015-12-01

    Full Text Available Dynamic glacier activity is increasingly observed through passive seismic monitoring. We analysed near-regional-scale seismicity on the Arctic archipelago of Svalbard to identify seismic icequake signals and to study their spatial–temporal distribution within the 14-year period from 2000 until 2013. This is the first study that uses seismic data recorded on permanent broadband stations to detect and locate icequakes in different regions of Spitsbergen, the main island of the archipelago. A temporary local seismic network and direct observations of glacier calving and surging were used to identify icequake sources. We observed a high number of icequakes with clear spectral peaks between 1 and 8 Hz in different parts of Spitsbergen. Spatial clusters of icequakes could be associated with individual grounded tidewater glaciers and exhibited clear seasonal variability each year with more signals observed during the melt season. Locations at the termini of glaciers, and correlation with visual calving observations in situ at Kronebreen, a glacier in the Kongsfjorden region, show that these icequakes were caused dominantly by calving. Indirect evidence for glacier surging through increased calving seismicity was found in 2003 at Tunabreen, a glacier in central Spitsbergen. Another type of icequake was observed in the area of the Nathorstbreen glacier system. Seismic events occurred upstream of the glacier within a short time period between January and May 2009 during the initial phase of a major glacier surge. This study is the first step towards the generation and implementation of an operational seismic monitoring strategy for glacier dynamics in Svalbard.

  9. Right and left amygdalae activation in patients with major depression receiving antidepressant treatment, as revealed by fMRI.

    Science.gov (United States)

    Chen, Yen-Ting; Huang, Min-Wei; Hung, I-Chung; Lane, Hsien-Yuan; Hou, Chun-Ju

    2014-10-08

    A differential contribution of the right and left amygdalae to affective information processing has been proposed. However, the direction of this lateralization has not been confirmed. In this study, we used a pre- and post-treatment (escitalopram) design to analyze the relative differences between neural activity in the right and left amygdalae during exposure to emotional stimuli in currently depressed patients. To the best of our knowledge, this study is to compare neural activity between the left and right amygdalae in people with depression. Our findings could lead to the development of parameters or biomarkers for depressive symptoms and treatment response. We used a pre-post-test design without a control group. Twenty currently depressed participants underwent an emotion processing task during fMRI. These participants were then treated with an antidepressant for 6 weeks. We used amygdala region-of-interest analysis to evaluate the hemodynamic response during exposure to colored emotional pictures. In total, thirteen of the 20 participants were placed into a separate group based on degree of response to antidepressants. The partial response group had an averaged HDRS score of 10.75 ± 2.25 and an averaged DBOLDLR signal of 189.18 ± 140.23 (m1 = 8), and the remitted group had an averaged HDRS score of 4.80 ± 1.64 and an averaged DBOLDLR signal of 421.26 ± 109.19 (m2 = 5). Each individual had lateralized amygdala activity, and the direction of asymmetry persisted following treatment. Amygdala responses to four types of emotional stimuli did not significantly change (p > 0.05) with treatment in either the right or the left amygdala. However, the difference in neural activity between the right and left amygdalae was greater after treatment, and the variation in neural activity was larger in the left amygdala. We found that the response between the right and left amygdala did not differ in terms of time series, although activity increased after pharmaceutical

  10. Protein expression profiling of inflammatory mediators in human temporal lobe epilepsy reveals co-activation of multiple chemokines and cytokines

    Directory of Open Access Journals (Sweden)

    Kan Anne A

    2012-08-01

    Full Text Available Abstract Mesial temporal lobe epilepsy (mTLE is a chronic and often treatment-refractory brain disorder characterized by recurrent seizures originating from the hippocampus. The pathogenic mechanisms underlying mTLE remain largely unknown. Recent clinical and experimental evidence supports a role of various inflammatory mediators in mTLE. Here, we performed protein expression profiling of 40 inflammatory mediators in surgical resection material from mTLE patients with and without hippocampal sclerosis, and autopsy controls using a multiplex bead-based immunoassay. In mTLE patients we identified 21 upregulated inflammatory mediators, including 10 cytokines and 7 chemokines. Many of these upregulated mediators have not previously been implicated in mTLE (for example, CCL22, IL-7 and IL-25. Comparing the three patient groups, two main hippocampal expression patterns could be distinguished, pattern I (for example, IL-10 and IL-25 showing increased expression in mTLE + HS patients compared to mTLE-HS and controls, and pattern II (for example, CCL4 and IL-7 showing increased expression in both mTLE groups compared to controls. Upregulation of a subset of inflammatory mediators (for example, IL-25 and IL-7 could not only be detected in the hippocampus of mTLE patients, but also in the neocortex. Principle component analysis was used to cluster the inflammatory mediators into several components. Follow-up analyses of the identified components revealed that the three patient groups could be discriminated based on their unique expression profiles. Immunocytochemistry showed that IL-25 IR (pattern I and CCL4 IR (pattern II were localized in astrocytes and microglia, whereas IL-25 IR was also detected in neurons. Our data shows co-activation of multiple inflammatory mediators in hippocampus and neocortex of mTLE patients, indicating activation of multiple pro- and anti-epileptogenic immune pathways in this disease.

  11. Resource potential methods using for efficiency of activities in the region increase

    Directory of Open Access Journals (Sweden)

    M. P. Vasiliev

    2016-01-01

    Full Text Available The article considers impact methods on the economic results, the effectiveness of the regional economic complex should be based on a high quality of the basic characteristics classification of the region state. Application composition techniques to ensure a comprehensive impact on the achievement of this goal should in synthesized form to union, adopt a target orientation of development of the region with the parameters objectively revealing his condition. Ensuring organizational, economic, financial and investment techniques to achieve the planned targets and requires specifying align resource potential of the region with the available capacity of the regional economic complex to promote economic growth, improve the efficiency of operations. The main characteristics of the potential resource opportunities in the region are the skill level of workers, the degree of depreciation of fixed assets and their renewability, increased innovation in the region, its branches and facilities, strengthening of competitive advantages, the annual average number of employees, the cost of fixed and current assets, financial stability. In the region the opportunity to potentially affect the ability of its structural components to achieve the financial and economic performance targets acts as efficiency ability to provide stable dynamics of regional production efficiency, enhance the level of benefits to achieve the planned efficiency used (consumed resource. Applying of certain methods or their entire structure, created to provide a comprehensive impact on the goal achievement, in the synthesized form of target orientation combines regional development with the parameters most objectively revealing his condition. Achieving the appropriate organizational, economic, financial, investment or other measures to achieve planned targets that are expressed by the level of efficiency of activity in the conditions of the most complete involvement and intensity of use in

  12. Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients.

    Science.gov (United States)

    Borgogna, Cinzia; Lanfredini, Simone; Peretti, Alberto; De Andrea, Marco; Zavattaro, Elisa; Colombo, Enrico; Quaglia, Marco; Boldorini, Renzo; Miglio, Umberto; Doorbar, John; Bavinck, Jan N Bouwes; Quint, Koen D; de Koning, Maurits N C; Landolfo, Santo; Gariglio, Marisa

    2014-08-01

    The aim of this study was to determine whether detection of β-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that β-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that β-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion.

  13. Trace metal depositional patterns from an open pit mining activity as revealed by archived avian gizzard contents.

    Science.gov (United States)

    Bendell, L I

    2011-02-15

    Archived samples of blue grouse (Dendragapus obscurus) gizzard contents, inclusive of grit, collected yearly between 1959 and 1970 were analyzed for cadmium, lead, zinc, and copper content. Approximately halfway through the 12-year sampling period, an open-pit copper mine began activities, then ceased operations 2 years later. Thus the archived samples provided a unique opportunity to determine if avian gizzard contents, inclusive of grit, could reveal patterns in the anthropogenic deposition of trace metals associated with mining activities. Gizzard concentrations of cadmium and copper strongly coincided with the onset of opening and the closing of the pit mining activity. Gizzard zinc and lead demonstrated significant among year variation; however, maximum concentrations did not correlate to mining activity. The archived gizzard contents did provide a useful tool for documenting trends in metal depositional patterns related to an anthropogenic activity. Further, blue grouse ingesting grit particles during the time of active mining activity would have been exposed to toxicologically significant levels of cadmium. Gizzard lead concentrations were also of toxicological significance but not related to mining activity. This type of "pulse" toxic metal exposure as a consequence of open-pit mining activity would not necessarily have been revealed through a "snap-shot" of soil, plant or avian tissue trace metal analysis post-mining activity. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Emotional outlook on life predicts increases in physical activity among initially inactive men.

    Science.gov (United States)

    Baruth, Meghan; Lee, Duck-Chul; Sui, Xuemei; Church, Timothy S; Marcus, Bess H; Wilcox, Sara; Blair, Steven N

    2011-04-01

    This study examined the relationship between emotional outlook on life and change in physical activity among inactive adults in the Aerobics Center Longitudinal Study. A total of 2,132 sedentary adults completed a baseline medical examination and returned for a follow-up examination at least 6 months later. Participants self-reported physical activity level and emotional outlook on life. Emotional outlook on life was significantly and positively related to physical activity participation at the follow-up visit in men but not women. Men who were usually very happy and optimistic at baseline had significantly greater increases in physical activity compared to men who were not happy. Men with a more positive outlook on life (e.g., happier) may be more likely to increase physical activity levels. Physical activity interventions targeting men may be more successful if they first increase happiness.

  15. Increased physical activity ameliorates high fat diet-induced bone resorption in mice

    Science.gov (United States)

    It has been recognized that mechanical stresses associated with physical activity (PA) have beneficial effects on increasing bone mineral density (BMD) and improving bone quality. On the other hand, high fat diet (HFD) and obesity increase bone marrow adiposity leading to increased excretion of pro-...

  16. Extracellular Histones Increase Tissue Factor Activity and Enhance Thrombin Generation by Human Blood Monocytes.

    Science.gov (United States)

    Gould, Travis J; Lysov, Zakhar; Swystun, Laura L; Dwivedi, Dhruva J; Zarychanski, Ryan; Fox-Robichaud, Alison E; Liaw, Patricia C

    2016-12-01

    Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. Tissue factor (TF) activity assays were performed on histone-treated THP-1 cells and blood monocytes. Exposure of monocytic cells to histones resulted in increases in TF activity, TF antigen, and phosphatidylserine exposure. Histones modulate the procoagulant activity via engagement of Toll-like receptors 2 and 4, and this effect was abrogated with inhibitory antibodies. Increased TF activity of histone-treated cells corresponded to enhanced thrombin generation in plasma determined by calibrated automated thrombography. Finally, TF activity was increased on monocytes exposed to plasma from septic patients, an effect that was attenuated in plasma from patients receiving unfractionated heparin (UFH). Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment.

  17. Selective activation of SHP2 activity by cisplatin revealed by a novel chemical probe-based assay

    International Nuclear Information System (INIS)

    Kuo, Chun-Chen; Chu, Chi-Yuan; Lin, Jing-Jer; Lo, Lee-Chiang

    2010-01-01

    Src homology-2 (SH2) domain-containing phosphatase 2 (SHP2) is known to participate in several different signaling pathways to mediate cell growth, survival, migration, and differentiation. However, due to the lack of proper analytical tools, it is unclear whether the phosphatase activity of SHP2 is activated in most studies. We have previously developed an activity-based probe LCL2 that formed covalent linkage with catalytically active protein tyrosine phosphatases (PTPs). Here, by combining LCL2 with a SHP2 specific antibody, we established an assay system that enables the direct monitoring of SHP2 activity upon cisplatin treatment of cancer cells. The protocol is advantageous over conventional colorimetric or in-gel PTP assays as it is specific and does not require the use of radioisotope reagents. Using this assay, we found SHP2 activity was selectively activated by cisplatin. Moreover, the activation of SHP2 appeared to be specific for cisplatin as other DNA damage agents failed to activate the activity. Although the role of SHP2 activation by cisplatin treatments is still unclear to us, our results provide the first direct evidence for the activation of SHP2 during cisplatin treatments. More importantly, the concept of using activity-based probe in conjunction with target-specific antibodies could be extended to other enzyme classes.

  18. Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Skouby, Sven O.; Kluft, Cornelis

    2011-01-01

    progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P≤0.001). OC use increased FSAP antigen by 25% and FSAP activity......Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... by 59% (P0.05). The relative increase in FSAP activity was significantly higher in women carrying the 1601GG genotype (63%) than in women carrying 1601GA genotype (50%) (P=0.01) and was associated with an increased activation of FVII. In conclusion: OC use increases the plasma measures of FSAP...

  19. Metaproteomics of cellulose methanisation under thermophilic conditions reveals a surprisingly high proteolytic activity.

    Science.gov (United States)

    Lü, Fan; Bize, Ariane; Guillot, Alain; Monnet, Véronique; Madigou, Céline; Chapleur, Olivier; Mazéas, Laurent; He, Pinjing; Bouchez, Théodore

    2014-01-01

    Cellulose is the most abundant biopolymer on Earth. Optimising energy recovery from this renewable but recalcitrant material is a key issue. The metaproteome expressed by thermophilic communities during cellulose anaerobic digestion was investigated in microcosms. By multiplying the analytical replicates (65 protein fractions analysed by MS/MS) and relying solely on public protein databases, more than 500 non-redundant protein functions were identified. The taxonomic community structure as inferred from the metaproteomic data set was in good overall agreement with 16S rRNA gene tag pyrosequencing and fluorescent in situ hybridisation analyses. Numerous functions related to cellulose and hemicellulose hydrolysis and fermentation catalysed by bacteria related to Caldicellulosiruptor spp. and Clostridium thermocellum were retrieved, indicating their key role in the cellulose-degradation process and also suggesting their complementary action. Despite the abundance of acetate as a major fermentation product, key methanogenesis enzymes from the acetoclastic pathway were not detected. In contrast, enzymes from the hydrogenotrophic pathway affiliated to Methanothermobacter were almost exclusively identified for methanogenesis, suggesting a syntrophic acetate oxidation process coupled to hydrogenotrophic methanogenesis. Isotopic analyses confirmed the high dominance of the hydrogenotrophic methanogenesis. Very surprising was the identification of an abundant proteolytic activity from Coprothermobacter proteolyticus strains, probably acting as scavenger and/or predator performing proteolysis and fermentation. Metaproteomics thus appeared as an efficient tool to unravel and characterise metabolic networks as well as ecological interactions during methanisation bioprocesses. More generally, metaproteomics provides direct functional insights at a limited cost, and its attractiveness should increase in the future as sequence databases are growing exponentially.

  20. Low Amount of Salinomycin Greatly Increases Akt Activation, but Reduces Activated p70S6K Levels

    Directory of Open Access Journals (Sweden)

    Sungpil Yoon

    2013-08-01

    Full Text Available The present study identified a novel salinomycin (Sal-sensitization mechanism in cancer cells. We analyzed the signal proteins Akt, Jnk, p38, Jak, and Erk1/2 in cancer cell lines that had arrested growth following low amounts of Sal treatment. We also tested the signal molecules PI3K, PDK1, GSK3β, p70S6K, mTOR, and PTEN to analyze the PI3K/Akt/mTOR pathway. The results showed that Sal sensitization positively correlates with large reductions in p70S6K activation. Interestingly, Akt was the only signal protein to be significantly activated by Sal treatment. The Akt activation appeared to require the PI3K pathway as its activation was abolished by the PI3K inhibitors LY294002 and wortmannin. The Akt activation by Sal was conserved in the other cell lines analyzed, which originated from other organs. Both Akt activation and C-PARP production were proportionally increased with increased doses of Sal. In addition, the increased levels of pAkt were not reduced over the time course of the experiment. Co-treatment with Akt inhibitors sensitized the Sal-treated cancer cells. The results thereby suggest that Akt activation is increased in cells that survive Sal treatment and resist the cytotoxic effect of Sal. Taken together; these results indicate that Akt activation may promote the resistance of cancer cells to Sal.

  1. Social capital, desire to increase physical activity and leisure-time physical activity: A population-based study.

    OpenAIRE

    Lindström, Martin

    2011-01-01

    OBJECTIVES: To investigate the associations between social capital (trust) and leisure-time physical activity. STUDY DESIGN: The 2004 Public Health Survey in Skåne is a cross-sectional study. METHODS: In total, 27,757 individuals aged 18-80 years answered a postal questionnaire (59% participation). Logistic regression models were used to investigate the associations between trust, desire to increase physical activity and leisure-time physical activity. RESULTS: ...

  2. Increased catalase activity by all-trans retinoic acid and its effect on radiosensitivity in rat glioma cells

    International Nuclear Information System (INIS)

    Jin, Hua; Jeon, Ha Yeun; Park, Woo Yoon; Kim, Won Dong; Ahn, Hee Yul; Yu, Jae Ran

    2005-01-01

    It has been reported that all-trans retinoic acid (ATRA) can inhibit glioma growing in vitro. However, clinical trials with ATRA alone in gliomas revealed modest results. ATRA has been shown to increase radiosensitivity in other tumor types, so combining radiation and ATRA would be one of alternatives to increase therapeutic efficacy in malignant gliomas. Thus, we intended to know the role of catalase, which is induced by ATRA, for radiosensitivity. If radiation-reduced reactive oxygen species (ROS) is removed by catalase, the effect of radiation will be reduced. A rat glioma cell line (36B10) was used for this study. The change of catalase activity and radiosensitivity by ATRA, with or without 3-amino-1, 2, 4-triazole (ATZ), a chemical inhibitor of catalase were measured. Catalase activity was measured by the decomposition of H 2 O 2 spectrophotometrically. Radiosensitivity was measured with clonogenic assay. Also ROS was measured using a 2, 7-dichlorofluores-cein diacetate spectrophotometrically. When 36B10 cells were exposed to 10, 25 and 50 μ M of ATRA for 48 h, the expression of catalase activity were increased with increasing concentration and incubation time of ATRA. Catalase activity was decreased with increasing the concentration of AT (1, 10 mM) dose-dependently. ROS was increased with ATRA and it was augmented with the combination of ATRA and radiation. ATZ decreased ROS production and increased cell survival in combination of ATRA and radiation despite the reduction of catalase. The increase of ROS is one of the reasons for the increased radiosensitivity in combination with ATRA. The catalase that is induced by ATRA doesn't decrease ROS production and radiosensitivity

  3. Estimates of increased black carbon emissions from electrostatic precipitators during powdered activated carbon injection for mercury emissions control.

    Science.gov (United States)

    Clack, Herek L

    2012-07-03

    The behavior of mercury sorbents within electrostatic precipitators (ESPs) is not well-understood, despite a decade or more of full-scale testing. Recent laboratory results suggest that powdered activated carbon exhibits somewhat different collection behavior than fly ash in an ESP and particulate filters located at the outlet of ESPs have shown evidence of powdered activated carbon penetration during full-scale tests of sorbent injection for mercury emissions control. The present analysis considers a range of assumed differential ESP collection efficiencies for powdered activated carbon as compared to fly ash. Estimated emission rates of submicrometer powdered activated carbon are compared to estimated emission rates of particulate carbon on submicrometer fly ash, each corresponding to its respective collection efficiency. To the extent that any emitted powdered activated carbon exhibits size and optical characteristics similar to black carbon, such emissions could effectively constitute an increase in black carbon emissions from coal-based stationary power generation. The results reveal that even for the low injection rates associated with chemically impregnated carbons, submicrometer particulate carbon emissions can easily double if the submicrometer fraction of the native fly ash has a low carbon content. Increasing sorbent injection rates, larger collection efficiency differentials as compared to fly ash, and decreasing sorbent particle size all lead to increases in the estimated submicrometer particulate carbon emissions.

  4. Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry

    Energy Technology Data Exchange (ETDEWEB)

    Krummenacher, Claude; Supekar, Vinit M.; Whitbeck, J. Charles; Lazear, Eric; Connolly, Sarah A.; Eisenberg, Roselyn J.; Cohen, Gary H.; Wiley, Don C.; Carfi, Andrea (UPENN); (IRBM); (CHLMM)

    2010-07-19

    Herpes simplex virus (HSV) entry into cells requires binding of the envelope glycoprotein D (gD) to one of several cell surface receptors. The 50 C-terminal residues of the gD ectodomain are essential for virus entry, but not for receptor binding. We have determined the structure of an unliganded gD molecule that includes these C-terminal residues. The structure reveals that the C-terminus is anchored near the N-terminal region and masks receptor-binding sites. Locking the C-terminus in the position observed in the crystals by an intramolecular disulfide bond abolished receptor binding and virus entry, demonstrating that this region of gD moves upon receptor binding. Similarly, a point mutant that would destabilize the C-terminus structure was nonfunctional for entry, despite increased affinity for receptors. We propose that a controlled displacement of the gD C-terminus upon receptor binding is an essential feature of HSV entry, ensuring the timely activation of membrane fusion.

  5. Increased active von Willebrand factor during disease development in the aging diabetic patient population.

    Science.gov (United States)

    Chen, Shuang Feng; Xia, Zuo Li; Han, Ji Ju; Wang, Yi Ting; Wang, Ji Yue; Pan, Shao Dong; Wu, Ya Ping; Zhang, Bin; Li, Guang Yao; Du, Jing Wei; Gao, Hen Qiang; de Groot, Philip G; de Laat, Bas; Hollestelle, Martine J

    2013-02-01

    Type 2 diabetes is known to cause endothelial activation resulting in the secretion of von Willebrand factor (VWF). We have shown that levels of VWF in a glycoprotein Ib-binding conformation are increased in specific clinical settings. The aim of the current study is to investigate whether active VWF levels increase during aging and the development of diabetes within the population of patients suffering from type 2 diabetes. Patients and controls were divided into two groups based on age: older and younger than 60 years of age. VWF antigen, VWF propeptide, VWF activation factor and total active VWF were measured. Patients older than 60 years of age had increased levels of total active VWF, VWF activation factor and VWF propeptide compared to younger patients and controls. All measured VWF parameters were associated with age in diabetic patients. Total active VWF and VWF propeptide correlated with the period of being diagnosed with diabetes. Regression analyses showed that especially the VWF activation factor was strongly associated with diabetes in patients older than 60 years of age. In conclusion, we found that the conformation of VWF could be involved in the disease process of diabetes and that the VWF in a glycoprotein Ib-binding conformation could play a role as risk marker during the development of diabetes in combination with an increase in age. Our study shows that the active quality of VWF was more important than the quantity.

  6. Activation of NADPH oxidase mediates increased endoplasmic reticulum stress and left ventricular remodeling after myocardial infarction in rabbits.

    Science.gov (United States)

    Li, Bao; Tian, Jing; Sun, Yi; Xu, Tao-Rui; Chi, Rui-Fang; Zhang, Xiao-Li; Hu, Xin-Ling; Zhang, Yue-An; Qin, Fu-Zhong; Zhang, Wei-Fang

    2015-05-01

    Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase activity and endoplasmic reticulum (ER) stress are increased after myocardial infarction (MI). In this study, we proposed to test whether activation of the NADPH oxidase in the remote non-infarcted myocardium mediates ER stress and left ventricular (LV) remodeling after MI. Rabbits with MI or sham operation were randomly assigned to orally receive an NADPH oxidase inhibitor apocynin or placebo for 30 days. The agents were administered beginning at 1 week after surgery. MI rabbits exhibited decreases in LV fractional shortening, LV ejection fraction and the first derivative of the LV pressure rise, which were abolished by apocynin treatment. NADPH oxidase Nox2 protein and mRNA expressions were increased in the remote non-infarcted myocardium after MI. Immunolabeling further revealed that Nox2 was increased in cardiac myocytes in the remote myocardium. The apocynin treatment prevented increases in the Nox2 expression, NADPH oxidase activity, oxidative stress, myocyte apoptosis and GRP78, CHOP and cleaved caspase 12 protein expression in the remote myocardium. The apocynin treatment also attenuated increases in myocyte diameter and cardiac fibrosis. In cultured H9C2 cardiomyocytes exposed to angiotensin II, an important stimulus for post-MI remodeling, Nox2 knockdown with siRNA significantly inhibited angiotensin II-induced NADPH oxidase activation, reactive oxygen species and GRP78 and CHOP protein expression. We conclude that NADPH oxidase inhibition attenuates increased ER stress in the remote non-infarcted myocardium and LV remodeling late after MI in rabbits. These findings suggest that the activation of NADPH oxidase in the remote non-infarcted myocardium mediates increased ER stress, contributing to myocyte apoptosis and LV remodeling after MI. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Increased Activity and Apoptosis of Eosinophils in Blister Fluids, Skin and Peripheral Blood of Patients with Bullous Pemphigoid.

    Science.gov (United States)

    Engmann, Judith; Rüdrich, Urda; Behrens, Georg; Papakonstantinou, Eleni; Gehring, Manuela; Kapp, Alexander; Raap, Ulrike

    2017-04-06

    Bullous pemphigoid (BP) is an autoimmune blistering skin disease that is more common in elderly individuals. The aim of this study was to determine the functional activity of eosinophils in patients with BP compared with healthy donors. Blood, skin and blister-derived eosinophils were strongly activated in patients with BP, seen by increased surface expression of CD69 compared with controls. CD11b was also increased in BP blood eosinophils, which may explain the striking accumulation of eosinophils in BP (1×106 per ml blister fluid). Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in blister fluid. BP eosinophils also released IL-6, IL-8 and IL-1α in BP blister fluids. Apoptosis in cultivated BP eosinophils was increased and accompanied by enhanced surface externalization of CD95. Caspase 3 positive eosinophils in lesional BP skin and blister fluid also showed the initiation of apoptosis. These results reveal novel pathophysiological aspects of BP, with a strong activation pattern and increased apoptosis of eosinophils in the peripheral blood, skin and blister fluids.

  8. Gonadotropin stimulates oocyte translation by increasing magnesium activity through intracellular potassium-magnesium exchange

    International Nuclear Information System (INIS)

    Horowitz, S.B.; Tluczek, L.J.

    1989-01-01

    We previously showed that gonadotropin increases the K + activity in Xenopus oocytes and that this is a signal for increased translation. However, K + need not act to control synthesis directly but may act through an unidentified downstream effector. Using microinjection to vary the salt content of oocytes and concomitantly measuring [ 3 H]leucine incorporation, we found that small changes in Mg 2+ greatly affect translation rates. (Ca 2+ had little influence.) By measuring intracellular ion activities, we found that oocyte cations existed in a buffer-like (ion-exchange) equilibrium in which K + and Mg 2+ are the preponderant monovalent and divalent cations. Hence, increasing cellular K + activity might increase translation by causing Mg 2+ activity to rise. If so, the increased translation rates produced by hormone treatment or K + injection would be prevented by EDTA, a Mg 2+ chelating agent. This prediction was tested and confirmed. We conclude that, when gonadotropin increases K + activity, the cell's internal ion-exchange equilibrium is altered thereby increasing Mg 2+ activity and this up-regulates translation

  9. The rate of synthesis and decomposition of tissue proteins in hypokinesia and increased muscular activity

    Science.gov (United States)

    Fedorov, I. V.; Chernyy, A. V.; Fedorov, A. I.

    1978-01-01

    During hypokinesia and physical loading (swimming) of rats, the radioactivity of skeletal muscle, liver, kidney, heart, and blood proteins was determined after administration of radioactive amino acids. Tissue protein synthesis decreased during hypokinesia, and decomposition increased. Both synthesis and decomposition increased during physical loading, but anabolic processes predominated in the total tissue balance. The weights of the animals decreased in hypokinesia and increased during increased muscle activity.

  10. Active Choice and Financial Incentives to Increase Rates of Screening Colonoscopy-A Randomized Controlled Trial.

    Science.gov (United States)

    Mehta, Shivan J; Feingold, Jordyn; Vandertuyn, Matthew; Niewood, Tess; Cox, Catherine; Doubeni, Chyke A; Volpp, Kevin G; Asch, David A

    2017-11-01

    Behavioral economic approaches could increase uptake for colorectal cancer screening. We performed a randomized controlled trial of 2245 employees to determine whether an email containing a phone number for scheduling (control), an email with the active choice to opt in or opt out (active choice), or the active choice email plus a $100 incentive (financial incentive) increased colonoscopy completion within 3 months. Higher proportions of participants in the financial incentive group underwent screening (3.7%) than in the control (1.6%) or active choice groups (1.5%) (P = .01 and P < .01). We found no difference in uptake of screening between the active choice and control groups (P = .88). The $100 conditional incentive modestly but significantly increased colonoscopy use. ClinicalTrials.gov no: NCT02660671. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Prediction of Positions of Active Compounds Makes It Possible To Increase Activity in Fragment-Based Drug Development

    Directory of Open Access Journals (Sweden)

    Yoshifumi Fukunishi

    2011-05-01

    Full Text Available We have developed a computational method that predicts the positions of active compounds, making it possible to increase activity as a fragment evolution strategy. We refer to the positions of these compounds as the active position. When an active fragment compound is found, the following lead generation process is performed, primarily to increase activity. In the current method, to predict the location of the active position, hydrogen atoms are replaced by small side chains, generating virtual compounds. These virtual compounds are docked to a target protein, and the docking scores (affinities are examined. The hydrogen atom that gives the virtual compound with good affinity should correspond to the active position and it should be replaced to generate a lead compound. This method was found to work well, with the prediction of the active position being 2 times more efficient than random synthesis. In the current study, 15 examples of lead generation were examined. The probability of finding active positions among all hydrogen atoms was 26%, and the current method accurately predicted 60% of the active positions.

  12. Using Carbohydrate Interaction Assays to Reveal Novel Binding Sites in Carbohydrate Active Enzymes

    DEFF Research Database (Denmark)

    Cockburn, Darrell; Wilkens, Casper; Dilokpimol, Adiphol

    2016-01-01

    Carbohydrate active enzymes often contain auxiliary binding sites located either on independent domains termed carbohydrate binding modules (CBMs) or as so-called surface binding sites (SBSs) on the catalytic module at a certain distance from the active site. The SBSs are usually critical...

  13. Focus group interviews reveal reasons for differences in the perception of disease activity in rheumatoid arthritis

    NARCIS (Netherlands)

    M.J. Walter (Margot); van’t Spijker, A. (Adriaan); A. Pasma (Annelieke); J.M.W. Hazes (Mieke); J.J. Luime (Jolanda)

    2017-01-01

    textabstractObjective: Doctors frequently see patients who have difficulties coping with their disease and rate their disease activity high, despite the fact that according to the doctors, the disease activity is low. This study explored the patients’ perspectives on this discordance that may help

  14. Teacher Knowledge for Active-Learning Instruction: Expert-Novice Comparison Reveals Differences

    Science.gov (United States)

    Auerbach, A. J.; Higgins, M.; Brickman, P.; Andrews, T. C.

    2018-01-01

    Active-learning strategies "can" improve science, technology, engineering, and mathematics (STEM) undergraduates' abilities to learn fundamental concepts and skills. However, the results instructors achieve vary substantially. One explanation for this is that instructors commonly implement active learning differently than intended. An…

  15. Increasing Physical Activity among Adults with Disabilities: Doctors Can Play a Key Role

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Dianna Carroll, a senior health scientist with CDC’s Division of Human Development and Disability, talks about the role of doctors and other health professionals in increasing physical activity among adults with disabilities.

  16. Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation.

    Science.gov (United States)

    Faustin, Benjamin; Lartigue, Lydia; Bruey, Jean-Marie; Luciano, Frederic; Sergienko, Eduard; Bailly-Maitre, Beatrice; Volkmann, Niels; Hanein, Dorit; Rouiller, Isabelle; Reed, John C

    2007-03-09

    Interleukin (IL)-1beta maturation is accomplished by caspase-1-mediated proteolysis, an essential element of innate immunity. NLRs constitute a recently recognized family of caspase-1-activating proteins, which contain a nucleotide-binding oligomerization domain and leucine-rich repeat (LRR) domains and which assemble into multiprotein complexes to create caspase-1-activating platforms called "inflammasomes." Using purified recombinant proteins, we have reconstituted the NALP1 inflammasome and have characterized the requirements for inflammasome assembly and caspase-1 activation. Oligomerization of NALP1 and activation of caspase-1 occur via a two-step mechanism, requiring microbial product, muramyl-dipeptide, a component of peptidoglycan, followed by ribonucleoside triphosphates. Caspase-1 activation by NALP1 does not require but is enhanced by adaptor protein ASC. The findings provide the biochemical basis for understanding how inflammasome assembly and function are regulated, and shed light on NALP1 as a direct sensor of bacterial components in host defense against pathogens.

  17. Statins Activate Human PPAR Promoter and Increase PPAR mRNA Expression and Activation in HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Makoto Seo

    2008-01-01

    Full Text Available Statins increase peroxisome proliferator-activated receptor (PPAR mRNA expression, but the mechanism of this increased PPAR production remains elusive. To examine the regulation of PPAR production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin on human PPAR promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1 Majority of statins enhanced PPAR promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPAR promoter. This enhancement may be mediated by statin-induced HNF-4. (2 PPAR mRNA expression was increased by statin treatment. (3 The PPAR levels in nuclear fractions were increased by statin treatment. (4 Simvastatin, pravastatin, and cerivastatin markedly enhanced transcriptional activity in 293T cells cotransfected with acyl-coenzyme A oxidase promoter and PPAR/RXR expression vectors. In summary, these data demonstrate that PPAR production and activation are upregulated through the PPAR promoter activity by statin treatment.

  18. Targeting Reductions in Sitting Time to Increase Physical Activity and Improve Health.

    Science.gov (United States)

    Keadle, Sarah K; Conroy, David E; Buman, Matthew P; Dunstan, David W; Matthews, Charles E

    2017-08-01

    : New evidence suggests that reductions in sedentary behavior may increase physical activity and improve health. These findings point to new behavioral targets for intervention and new ways to think about intervening to increase overall physical activity in the population. This report provides a knowledge update reflecting the rapid accumulation of new evidence related to sedentary behavior and health among adults. Recent observational studies suggest that leveraging the time-inverse relationship between sedentary and active behaviors by replacing sitting with standing, light- or moderate-intensity activity can have important health benefits, particularly among less active adults. Clinical studies are providing evidence of the probable physiologic mechanisms underlying these associations, as well as insights into the cardiometabolic impact of breaking up and reducing sedentary behavior. In contrast to the well-established behavioral theories that guide the development and dissemination of evidence-based interventions to increase moderate- to vigorous-intensity physical activity, much less is known about how to reduce sedentary time to increase daily activities. It has become clear that the environmental, social, and individual level determinants for sedentary time are distinct from those linked to the adoption and maintenance of moderate- to vigorous-intensity physical activity. As a result, novel intervention strategies that focus on sitting and lower-intensity activities by leveraging the surrounding environment (e.g., workplace, school, and home) as well as individual-level cues and habits of sedentary behavior are being tested to increase the potency of interventions designed to increase overall physical activity. Herein we summarize the solutions-oriented research across the behavioral research framework, with a focus on highlighting areas of synergy across disciplines and identifying gaps for future research.

  19. Turning the tide: national policy approaches to increasing physical activity in seven European countries.

    Science.gov (United States)

    Bull, Fiona; Milton, Karen; Kahlmeier, Sonja; Arlotti, Alberto; Juričan, Andrea Backović; Belander, Olov; Martin, Brian; Martin-Diener, Eva; Marques, Ana; Mota, Jorge; Vasankari, Tommi; Vlasveld, Anita

    2015-06-01

    Physical inactivity is one of the four leading behavioural risk factors for non-communicable disease (NCD). Like tobacco control, increasing levels of health-enhancing physical activity (HEPA) will require a national policy framework providing direction and a clear set of actions. Despite frequent calls, there has been insufficient progress on policy development in the majority of countries around the world. This study sought and summarised national HEPA policy in seven European countries (Finland, Italy, the Netherlands, Norway, Portugal, Slovenia and Switzerland). Data collection used a policy audit tool (PAT), a 27-item instrument structured into four sections. All countries reported some legislation or policy across the sectors of education, sport and health. Only some countries reported supportive policy in the transport and environment sectors. Five countries reported a stand-alone HEPA policy and six countries reported national recommendations. HEPA prevalence targets varied in magnitude and specificity and the presence of other relevant goals from different sectors highlighted the opportunity for joint action. Evaluation and the use of scientific evidence were endorsed but described as weak in practice. Only two countries reported a national multisector coordinating committee and most countries reported challenges with partnerships on different levels of policy implementation. Bringing together the key components for success within a national HEPA policy framework is not simple. This in-depth policy audit and country comparison highlighted similarities and differences and revealed new opportunities for consideration by other countries. These examples can inform countries within and beyond Europe and guide the development of national HEPA policy within the NCD prevention agenda. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Plains zebra (Equus quagga) adrenocortical activity increases during times of large aggregations in the Serengeti ecosystem.

    Science.gov (United States)

    Seeber, P A; Franz, M; Dehnhard, M; Ganswindt, A; Greenwood, A D; East, M L

    2018-04-20

    Adverse environmental stimuli (stressors) activate the hypothalamic-pituitary-adrenal axis and contribute to allostatic load. This study investigates the contribution of environmental stressors and life history stage to allostatic load in a migratory population of plains zebras (Equus quagga) in the Serengeti ecosystem, in Tanzania, which experiences large local variations in aggregation. We expected higher fGCM response to the environmental stressors of feeding competition, predation pressure and unpredictable social relationships in larger than in smaller aggregations, and in animals at energetically costly life history stages. As the study was conducted during the 2016 El Niño, we did not expect food quality of forage or a lack of water to strongly affect fGCM responses in the dry season. We measured fecal glucocorticoid metabolite (fGCM) concentrations using an enzyme immunoassay (EIA) targeting 11β-hydroxyetiocholanolone and validated its reliability in captive plains zebras. Our results revealed significantly higher fGCM concentrations 1) in large aggregations than in smaller groupings, and 2) in band stallions than in bachelor males. Concentrations of fGCM were not significantly higher in females at the energetically costly life stage of late pregnancy/lactation. The higher allostatic load of stallions associated with females, than bachelor males is likely caused by social stressors. In conclusion, migratory zebras have elevated allostatic loads in large aggregations that probably result from their combined responses to increased feeding competition, predation pressure and various social stressors. Further research is required to disentangle the contribution of these stressors to allostatic load in migratory populations. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Seeing Is Eating: How and When Activation of a Negative Stereotype Increases Stereotype-Conducive Behavior

    OpenAIRE

    Margaret C. Campbell; Gina S. Mohr

    2011-01-01

    This research investigates the effect of activation of a negative stereotype on behaviors that are perceived to increase the chance of becoming a member of the stereotyped group. Activation of a negative stereotype (the overweight stereotype) is shown to lead to stereotype-consistent goal commitment (low health goal commitment), which partially explains increases in stereotype-conducive behavior (eating indulgent foods). Two theoretically relevant moderators are proposed and supported. Increa...

  2. Increased PDGFRα Activation Disrupts Connective Tissue Development and Drives Systemic Fibrosis

    OpenAIRE

    Olson, Lorin E.; Soriano, Philippe

    2009-01-01

    PDGF signaling regulates the development of mesenchymal cell types in the embryo and in the adult, but the role of receptor activation in tissue homeostasis has not been investigated. We have generated conditional knockin mice with mutations in PDGFRα that drive increased kinase activity under the control of the endogenous PDGFRα promoter. In embryos, increased PDGFRα signaling leads to hyperplasia of stromal fibroblasts that disturbs normal smooth muscle tissue in radially patterned organs. ...

  3. Knockin of Cre Gene at Ins2 Locus Reveals No Cre Activity in Mouse Hypothalamic Neurons.

    Science.gov (United States)

    Li, Ling; Gao, Lin; Wang, Kejia; Ma, Xianhua; Chang, Xusheng; Shi, Jian-Hui; Zhang, Ye; Yin, Kai; Liu, Zhimin; Shi, Yuguang; Xie, Zhifang; Zhang, Weiping J

    2016-02-02

    The recombination efficiency and cell specificity of Cre driver lines are critical for exploring pancreatic β cell biology with the Cre/LoxP approach. Some commonly used Cre lines are based on the short Ins2 promoter fragment and show recombination activity in hypothalamic neurons; however, whether this stems from endogenous Ins2 promoter activity remains controversial. In this study, we generated Ins2-Cre knockin mice with a targeted insertion of IRES-Cre at the Ins2 locus and demonstrated with a cell lineage tracing study that the Ins2 gene is not transcriptionally active in the hypothalamus. The Ins2-Cre driver line displayed robust Cre expression and activity in pancreatic β cells without significant alterations in insulin expression. In the brain, Cre activity was mainly restricted to the choroid plexus, without significant recombination detected in the hippocampus or hypothalamus by the LacZ or fluorescent tdTomato reporters. Furthermore, Ins2-Cre mice exhibited normal glucose tolerance and insulin secretion upon glucose stimulation in vivo. In conclusion, this Ins2-Cre driver line allowed high-fidelity detection of endogenous Ins2 promoter activity in vivo, and the negative activity in the hypothalamus demonstrated that this system is a promising alternative tool for studying β cell biology.

  4. Increasing Children's Voluntary Physical Activity Outside of School Hours Through Targeting Social Cognitive Theory Variables.

    Science.gov (United States)

    Annesi, James J; Walsh, Stephanie M; Greenwood, Brittney L

    2016-10-01

    Volume of moderate-to-vigorous physical activity completed during the elementary school day is insufficient, and associated with health risks. Improvements in theory-based psychosocial factors might facilitate increased out-of-school physical activity. A behaviorally based after-school care protocol, Youth Fit 4 Life, was tested for its association with increased voluntary, out-of-school physical activity and improvements in its theory-based psychosocial predictors in 9- to 12-year-olds. Increases over 12 weeks in out-of-school physical activity, and improvements in self-regulation for physical activity, exercise self-efficacy, and mood, were significantly greater in the Youth Fit 4 Life group (n = 88) when contrasted with a typical care control group (n = 57). Changes in the 3 psychosocial variables significantly mediated the group-physical activity change relationship (R(2) = .31, P theory-based psychosocial changes within a structured after-school care physical activity program was associated with increases in children's overall time being physically active. After replication, large scale application will be warranted. © The Author(s) 2016.

  5. Increased MMP-2 activity during intervertebral disc degeneration is correlated to MMP-14 levels

    NARCIS (Netherlands)

    Rutges, J. P. H. J.; Kummer, J. A.; Oner, F. C.; Verbout, A. J.; Roestenburg, H. J. A.; Dhert, W. J. A.; Creemers, L. B.

    Intervertebral disc (IVD) degeneration is associated with the increased expression of several matrix metalloproteinases (MMPs), in particular MMP-2. However, little is known about the actual activity of MMP-2 in healthy and degenerated discs, or what mechanisms are involved in its activation. A

  6. Focused Campaign Increases Activity among Participants in "Nature's Notebook," a Citizen Science Project

    Science.gov (United States)

    Crimmins, Theresa M.; Weltzin, Jake F.; Rosemartin, Alyssa H.; Surina, Echo M.; Marsh, Lee; Denny, Ellen G.

    2014-01-01

    Science projects, which engage non-professional scientists in one or more stages of scientific research, have been gaining popularity; yet maintaining participants' activity level over time remains a challenge. The objective of this study was to evaluate the potential for a short-term, focused campaign to increase participant activity in a…

  7. Increase the Performance of Companies in the Energy Sector by Implementing the Activity-Based Costing

    OpenAIRE

    Letitia-Maria Rof; Sorinel Capusneanu

    2015-01-01

    This article highlights the increasing performances as result of implementation stages of the ActivityBased Costing in the companies operating in the energy sector in Romania. There are presented some aspects of the usefulness of applying the Activity-Based Costing in the energy sector and the advantages it offers compared to traditional costing. There are also outlined the steps for applying the Activity-Based Costing and its implementation in the largest hydropower producer in Romania. The ...

  8. Serine Proteolytic Pathway Activation Reveals an Expanded Ensemble of Wound Response Genes in Drosophila

    Science.gov (United States)

    Patterson, Rachel A.; Juarez, Michelle T.; Hermann, Anita; Sasik, Roman; Hardiman, Gary; McGinnis, William

    2013-01-01

    After injury to the animal epidermis, a variety of genes are transcriptionally activated in nearby cells to regenerate the missing cells and facilitate barrier repair. The range and types of diffusible wound signals that are produced by damaged epidermis and function to activate repair genes during epidermal regeneration remains a subject of very active study in many animals. In Drosophila embryos, we have discovered that serine protease function is locally activated around wound sites, and is also required for localized activation of epidermal repair genes. The serine protease trypsin is sufficient to induce a striking global epidermal wound response without inflicting cell death or compromising the integrity of the epithelial barrier. We developed a trypsin wounding treatment as an amplification tool to more fully understand the changes in the Drosophila transcriptome that occur after epidermal injury. By comparing our array results with similar results on mammalian skin wounding we can see which evolutionarily conserved pathways are activated after epidermal wounding in very diverse animals. Our innovative serine protease-mediated wounding protocol allowed us to identify 8 additional genes that are activated in epidermal cells in the immediate vicinity of puncture wounds, and the functions of many of these genes suggest novel genetic pathways that may control epidermal wound repair. Additionally, our data augments the evidence that clean puncture wounding can mount a powerful innate immune transcriptional response, with different innate immune genes being activated in an interesting variety of ways. These include puncture-induced activation only in epidermal cells in the immediate vicinity of wounds, or in all epidermal cells, or specifically in the fat body, or in multiple tissues. PMID:23637905

  9. Correlations between human mobility and social interaction reveal general activity patterns

    DEFF Research Database (Denmark)

    Mollgaard, Anders; Jørgensen, Sune Lehmann; Mathiesen, Joachim

    2017-01-01

    activity types, namely communication, motion, and physical proximity by analyzing data collected from smartphones distributed among 638 individuals. We explore two central questions: Which underlying principles govern the formation of the activity patterns? Are the patterns specific to each individual...... or shared across the entire population? We find that statistics of the entire population allows us to successfully predict 71% of the activity and 85% of the inactivity involved in communication, mobility, and physical proximity. Surprisingly, individual level statistics only result in marginally better...... they be of social or of physical character....

  10. Engaging Fathers to Increase Physical Activity in Girls: The "Dads And Daughters Exercising and Empowered" (DADEE) Randomized Controlled Trial.

    Science.gov (United States)

    Morgan, Philip J; Young, Myles D; Barnes, Alyce T; Eather, Narelle; Pollock, Emma R; Lubans, David R

    2018-04-10

    Existing strategies to increase girls' physical activity levels have seen limited success. Fathers may influence their children's physical activity, but often spend more time with their sons and rarely participate in family-based programs. To test a novel program designed to increase the physical activity levels of fathers and their daughters. In a two-arm RCT, 115 fathers (29-53 years) and 153 daughters (4-12 years) were randomized to (i) the "Dads And Daughters Exercising and Empowered" (DADEE) program, or (ii) a wait-list control. The 8-week program included weekly educational and practical sessions plus home tasks. Assessments were at baseline, 2 months (postintervention), and 9 months. The primary outcomes were father-daughter physical activity levels (pedometry). Secondary outcomes included screen-time, daughters' fundamental movement skill proficiency (FMS: perceived and objective), and fathers' physical activity parenting practices. Primary outcome data were obtained from 88% of daughters and 90% of fathers at 9 months. Intention-to-treat analyses revealed favorable group-by-time effects for physical activity in daughters (p = .02, d = 0.4) and fathers (p competence (objective: d = 1.1-1.2; perceived: d = 0.4-0.6), a range of fathers' physical activity parenting practices (d = 0.3-0.8), and screen-time for daughters (d = 0.5-0.8) and fathers (d = 0.4-0.6, postintervention only). Program satisfaction and attendance were very high. This study provided the first experimental evidence that efforts to increase physical activity behavior in preadolescent girls would benefit from a meaningful engagement of fathers. Clinical Trial information: Australian New Zealand Clinical Trials Registry: ACTRN12615000022561.

  11. Different patterns of auditory cortex activation revealed by functional magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Formisano, E; Pepino, A; Bracale, M [Department of Electronic Engineering, Biomedical Unit, Universita di Napoli, Federic II, Italy, Via Claudio 21, 80125 Napoli (Italy); Di Salle, F [Department of Biomorphological and Functional Sciences, Radiologucal Unit, Universita di Napoli, Federic II, Italy, Via Claudio 21, 80125 Napoli (Italy); Lanfermann, H; Zanella, F E [Department of Neuroradiology, J.W. Goethe Universitat, Frankfurt/M. (Germany)

    1999-12-31

    In the last few years, functional Magnetic Resonance Imaging (fMRI) has been widely accepted as an effective tool for mapping brain activities in both the sensorimotor and the cognitive field. The present work aims to assess the possibility of using fMRI methods to study the cortical response to different acoustic stimuli. Furthermore, we refer to recent data collected at Frankfurt University on the cortical pattern of auditory hallucinations. Healthy subjects showed broad bilateral activation, mostly located in the transverse gyrus of Heschl. The analysis of the cortical activation induced by different stimuli has pointed out a remarkable difference in the spatial and temporal features of the auditory cortex response to pulsed tones and pure tones. The activated areas during episodes of auditory hallucinations match the location of primary auditory cortex as defined in control measurements with the same patients and in the experiments on healthy subjects. (authors) 17 refs., 4 figs.

  12. Spores of most common airborne fungi reveal no ice nucleation activity

    Science.gov (United States)

    Pummer, B. G.; Atanasova, L.; Bauer, H.; Bernardi, J.; Druzhinina, I. S.; Grothe, H.

    2013-06-01

    Fungal spores are ubiquitous biological aerosols, which are considered to show ice nucleation (IN) activity. In this study the respective IN activity was tested in oil emulsion in the immersion freezing mode. The focus was laid on species of economical, ecological or sanitary significance. For the first time, not only common moulds, but also edible mushrooms (Basidiomycota, Agaricomycetes) were investigated, as they contribute massively to the total amount of fungal spores in the atmosphere. Only Fusarium avenaceum showed freezing events at low subzero-temperatures, while the other investigated fungal spores showed no significant IN activity. Furthermore, we selected a set of fungal strains from different sites and exposed them to occasional freezing stress during cultivation. Although the total protein expression was altered by this treatment, it had no significant impact on the IN activity.

  13. Different patterns of auditory cortex activation revealed by functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Formisano, E.; Pepino, A.; Bracale, M.; Di Salle, F.; Lanfermann, H.; Zanella, F.E.

    1998-01-01

    In the last few years, functional Magnetic Resonance Imaging (fMRI) has been widely accepted as an effective tool for mapping brain activities in both the sensorimotor and the cognitive field. The present work aims to assess the possibility of using fMRI methods to study the cortical response to different acoustic stimuli. Furthermore, we refer to recent data collected at Frankfurt University on the cortical pattern of auditory hallucinations. Healthy subjects showed broad bilateral activation, mostly located in the transverse gyrus of Heschl. The analysis of the cortical activation induced by different stimuli has pointed out a remarkable difference in the spatial and temporal features of the auditory cortex response to pulsed tones and pure tones. The activated areas during episodes of auditory hallucinations match the location of primary auditory cortex as defined in control measurements with the same patients and in the experiments on healthy subjects. (authors)

  14. Teacher Knowledge for Active-Learning Instruction: Expert-Novice Comparison Reveals Differences.

    Science.gov (United States)

    Auerbach, A J; Higgins, M; Brickman, P; Andrews, T C

    2018-01-01

    Active-learning strategies can improve science, technology, engineering, and mathematics (STEM) undergraduates' abilities to learn fundamental concepts and skills. However, the results instructors achieve vary substantially. One explanation for this is that instructors commonly implement active learning differently than intended. An important factor affecting how instructors implement active learning is knowledge of teaching and learning. We aimed to discover knowledge that is important to effective active learning in large undergraduate courses. We developed a lesson-analysis instrument to elicit teacher knowledge, drawing on the theoretical construct of teacher noticing. We compared the knowledge used by expert ( n = 14) and novice ( n = 29) active-learning instructors as they analyzed lessons. Experts and novices differed in what they noticed, with experts more commonly considering how instructors hold students accountable, topic-specific student difficulties, whether the instructor elicited and responded to student thinking, and opportunities students had to generate their own ideas and work. Experts were also better able to support their lesson analyses with reasoning. This work provides foundational knowledge for the future design of preparation and support for instructors adopting active learning. Improving teacher knowledge will improve the implementation of active learning, which will be necessary to widely realize the potential benefits of active learning in undergraduate STEM. © 2018 A. J. Auerbach et al. CBE—Life Sciences Education © 2018 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  15. Active mechanics in living oocytes reveal molecular-scale force kinetics

    Science.gov (United States)

    Ahmed, Wylie; Fodor, Etienne; Almonacid, Maria; Bussonnier, Matthias; Verlhac, Marie-Helene; Gov, Nir; Visco, Paolo; van Wijland, Frederic; Betz, Timo

    Unlike traditional materials, living cells actively generate forces at the molecular scale that change their structure and mechanical properties. This nonequilibrium activity is essential for cellular function, and drives processes such as cell division. Single molecule studies have uncovered the detailed force kinetics of isolated motor proteins in-vitro, however their behavior in-vivo has been elusive due to the complex environment inside the cell. Here, we quantify active forces and intracellular mechanics in living oocytes using in-vivo optical trapping and laser interferometry of endogenous vesicles. We integrate an experimental and theoretical framework to connect mesoscopic measurements of nonequilibrium properties to the underlying molecular- scale force kinetics. Our results show that force generation by myosin-V drives the cytoplasmic-skeleton out-of-equilibrium (at frequencies below 300 Hz) and actively softens the environment. In vivo myosin-V activity generates a force of F ~ 0 . 4 pN, with a power-stroke of length Δx ~ 20 nm and duration τ ~ 300 μs, that drives vesicle motion at vv ~ 320 nm/s. This framework is widely applicable to characterize living cells and other soft active materials.

  16. Correlations between human mobility and social interaction reveal general activity patterns.

    Science.gov (United States)

    Mollgaard, Anders; Lehmann, Sune; Mathiesen, Joachim

    2017-01-01

    A day in the life of a person involves a broad range of activities which are common across many people. Going beyond diurnal cycles, a central question is: to what extent do individuals act according to patterns shared across an entire population? Here we investigate the interplay between different activity types, namely communication, motion, and physical proximity by analyzing data collected from smartphones distributed among 638 individuals. We explore two central questions: Which underlying principles govern the formation of the activity patterns? Are the patterns specific to each individual or shared across the entire population? We find that statistics of the entire population allows us to successfully predict 71% of the activity and 85% of the inactivity involved in communication, mobility, and physical proximity. Surprisingly, individual level statistics only result in marginally better predictions, indicating that a majority of activity patterns are shared across our sample population. Finally, we predict short-term activity patterns using a generalized linear model, which suggests that a simple linear description might be sufficient to explain a wide range of actions, whether they be of social or of physical character.

  17. Receptor activity-independent recruitment of βarrestin2 reveals specific signalling modes

    Science.gov (United States)

    Terrillon, Sonia; Bouvier, Michel

    2004-01-01

    The roles of βarrestins in regulating G protein coupling and receptor endocytosis following agonist stimulation of G protein-coupled receptors are well characterised. However, their ability to act on their own as direct modulators or activators of signalling remains poorly characterised. Here, βarrestin2 intrinsic signalling properties were assessed by forcing the recruitment of this accessory protein to vasopressin V1a or V2 receptors independently of agonist-promoted activation of the receptors. Such induction of a stable interaction with βarrestin2 initiated receptor endocytosis leading to intracellular accumulation of the βarrestin/receptor complexes. Interestingly, βarrestin2 association to a single receptor protomer was sufficient to elicit receptor dimer internalisation. In addition to recapitulating βarrestin2 classical actions on receptor trafficking, the receptor activity-independent recruitment of βarrestin2 activated the extracellular signal-regulated kinases. In the latter case, recruitment to the receptor itself was not required since kinase activation could be mediated by βarrestin2 translocation to the plasma membrane in the absence of any interacting receptor. These data demonstrate that βarrestin2 can act as a ‘bonafide' signalling molecule even in the absence of activated receptor. PMID:15385966

  18. Activity patterns of free-ranging koalas (Phascolarctos cinereus revealed by accelerometry.

    Directory of Open Access Journals (Sweden)

    Michelle A Ryan

    Full Text Available An understanding of koala activity patterns is important for measuring the behavioral response of this species to environmental change, but to date has been limited by the logistical challenges of traditional field methodologies. We addressed this knowledge gap by using tri-axial accelerometer data loggers attached to VHF radio collars to examine activity patterns of adult male and female koalas in a high-density population at Cape Otway, Victoria, Australia. Data were obtained from 27 adult koalas over two 7-d periods during the breeding season: 12 in the early-breeding season in November 2010, and 15 in the late-breeding season in January 2011. Multiple 15 minute observation blocks on each animal were used for validation of activity patterns determined from the accelerometer data loggers. Accelerometry was effective in distinguishing between inactive (sleeping, resting and active (grooming, feeding and moving behaviors. Koalas were more active during the early-breeding season with a higher index of movement (overall dynamic body acceleration [ODBA] for both males and females. Koalas showed a distinct temporal pattern of behavior, with most activity occurring from mid-afternoon to early morning. Accelerometry has potential for examining fine-scale behavior of a wide range of arboreal and terrestrial species.

  19. Activity patterns of free-ranging koalas (Phascolarctos cinereus) revealed by accelerometry.

    Science.gov (United States)

    Ryan, Michelle A; Whisson, Desley A; Holland, Greg J; Arnould, John P Y

    2013-01-01

    An understanding of koala activity patterns is important for measuring the behavioral response of this species to environmental change, but to date has been limited by the logistical challenges of traditional field methodologies. We addressed this knowledge gap by using tri-axial accelerometer data loggers attached to VHF radio collars to examine activity patterns of adult male and female koalas in a high-density population at Cape Otway, Victoria, Australia. Data were obtained from 27 adult koalas over two 7-d periods during the breeding season: 12 in the early-breeding season in November 2010, and 15 in the late-breeding season in January 2011. Multiple 15 minute observation blocks on each animal were used for validation of activity patterns determined from the accelerometer data loggers. Accelerometry was effective in distinguishing between inactive (sleeping, resting) and active (grooming, feeding and moving) behaviors. Koalas were more active during the early-breeding season with a higher index of movement (overall dynamic body acceleration [ODBA]) for both males and females. Koalas showed a distinct temporal pattern of behavior, with most activity occurring from mid-afternoon to early morning. Accelerometry has potential for examining fine-scale behavior of a wide range of arboreal and terrestrial species.

  20. Unbiased cell quantification reveals a continued increase in the number of neocortical neurones during early post-natal development in mice

    DEFF Research Database (Denmark)

    Lyck, Lise; Krøigård, Thomas; Finsen, Bente

    2007-01-01

    The post-natal growth spurt of the mammalian neocortex has been attributed to maturation of dendritic arborizations, growth and myelination of axons, and addition of glia. It is unclear whether this growth may also involve recruitment of additional neurones. Using stereological methods, we analysed...... the number of neurones and glia in the neocortex during post-natal development in two separate strains of mice. Cell counting by the optical fractionator revealed that the number of neurones increased 80-100% from the time of birth to post-natal day (P)16, followed by a reduction by approximately 25...... was delayed until P16. The number of glia reached its maximum at P16, whereas the number of oligodendroglia, identified using a transgenic marker, increased until P55, the latest time of observation. Neurones continued to accumulate in the developing neocortex during the first 2 weeks of post...

  1. Increased activities of mitochondrial enzymes in white adipose tissue in trained rats

    DEFF Research Database (Denmark)

    Stallknecht, B; Vinten, J; Ploug, T

    1991-01-01

    of 8-12 rats were swim trained for 10 wk or served as either sedentary, sham swim-trained, or cold-stressed controls. White adipose tissue was removed, and the activities of the respiratory chain enzyme cytochrome-c oxidase (CCO) and of the enzyme malate dehydrogenase (MDH), which participates...... 0.05). In female rats the CCO activity expressed per milligram protein was increased 4.5-fold in the trained compared with the sedentary control rats (P less than 0.01). Neither cold stress nor sham swim training increased CCO or MDH activities in white adipose tissue (P greater than 0...

  2. Building an urban park increases the intention of adults to practice physical activity

    Directory of Open Access Journals (Sweden)

    Raphaelly Machado Felix

    Full Text Available Abstract Physical activity levels in adults are low and strategies should be put in place to change this. The aim of this study was to investigate whether building an urban park can increase adult neighborhood residents' intentions to partake in physical activity. In total, 395 adults living near where the park was being built participated in the study. The following information was collected: sociodemographic characteristics, current physical activity levels, and intention to use the park for physical activity. Around 80% of the subjects intended to use the park for physical activity. This frequency was higher among those who were classified as physically active and gradually higher as the distance between the home of the subject and the park decreased (p < 0.05. The offer of a public leisure space can contribute positively to changing population behavior related to regular physical activity.

  3. Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome.

    Directory of Open Access Journals (Sweden)

    Xianming Zhang

    Full Text Available It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS, but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS.Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAPSB and abdominal muscle paralysis group (BIPAPAP. All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH2O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO2 of 35-60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment.For the comparable ventilator setting, as compared with BIPAPSB group, the BIPAPAP group presented higher EELV (427±47 vs. 366±38 ml and oxygenation index (293±36 vs. 226±31 mmHg, lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7 and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9 in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAPAP group (22.5±2.0 vs. 25.2±2.1.Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.

  4. Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Zhang, Xianming; Wu, Weiliang; Zhu, Yongcheng; Jiang, Ying; Du, Juan; Chen, Rongchang

    2016-01-01

    It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAPSB) and abdominal muscle paralysis group (BIPAPAP). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH2O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO2 of 35-60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. For the comparable ventilator setting, as compared with BIPAPSB group, the BIPAPAP group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAPAP group (22.5±2.0 vs. 25.2±2.1). Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.

  5. A systematic review of workplace health promotion interventions for increasing physical activity.

    Science.gov (United States)

    Malik, Sumaira H; Blake, Holly; Suggs, L Suzanne

    2014-02-01

    The benefits of an active lifestyle are widely documented, yet studies show that only a small proportion of adults engage in sufficient levels of physical activity. The workplace presents an ideal avenue for delivering initiatives to promote physical activity, overcoming commonly cited barriers such as a 'lack of time' and providing access to a large intersection of society. The purpose of this study was to (1) explore the types of interventions workplaces implement to promote physical activity among staff, (2) describe the characteristics of those interventions, (3) understand whether these interventions positively impact on activity levels, and (4) assess the methodological quality of studies. A systematic review of workplace physical activity interventions published up to April 2011 was conducted to identify types of interventions and their outcomes. Of the 58 studies included, the majority utilized health promotion initiatives. There were six physical activity/exercise interventions, 13 counselling/support interventions, and 39 health promotion messages/information interventions. Thirty-two of these studies showed a statistically significant increase in a measure of physical activity against a control group at follow-up. While the studies included in this review show some evidence that workplace physical activity interventions can be efficacious, overall the results are inconclusive. Despite the proliferation of research in this area, there is still a need for more well-designed studies to fully determine the effectiveness of workplace interventions for increasing physical activity and to identify the types of interventions that show the most promise. © 2013 The British Psychological Society.

  6. Active Early: one-year policy intervention to increase physical activity among early care and education programs in Wisconsin

    Directory of Open Access Journals (Sweden)

    Tara L. LaRowe

    2016-07-01

    Full Text Available Abstract Background Early childcare and education (ECE is a prime setting for obesity prevention and the establishment of healthy behaviors. The objective of this quasi-experimental study was to examine the efficacy of the Active Early guide, which includes evidenced-based approaches, provider resources, and training, to improve physical activity opportunities through structured (i.e. teacher-led activity and environmental changes thereby increasing physical activity among children, ages 2–5 years, in the ECE setting. Methods Twenty ECE programs in Wisconsin, 7 family and 13 group, were included. An 80-page guide, Active Early, was developed by experts and statewide partners in the fields of ECE, public health, and physical activity and was revised by ECE providers prior to implementation. Over 12 months, ECE programs received on-site training and technical assistance to implement the strategies and resources provided in the Active Early guide. Main outcome measures included observed minutes of teacher-led physical activity, physical activity environment measured by the Environment and Policy Assessment and Observation (EPAO instrument, and child physical activity levels via accelerometry. All measures were collected at baseline, 6 months, and 12 months and were analyzed for changes over time. Results Observed teacher-led physical activity significantly increased from 30.9 ± 22.7 min at baseline to 82.3 ± 41.3 min at 12 months. The change in percent time children spent in sedentary activity decreased significantly after 12 months (−4.4 ± 14.2 % time, −29.2 ± 2.6 min, p < 0.02. Additionally, as teacher led-activity increased, percent time children were sedentary decreased (r = −0.37, p < 0.05 and percent time spent in light physical activity increased (r = 0.35, p < 0.05. Among all ECE programs, the physical activity environment improved significantly as indicated by multiple sub-scales of

  7. Social interaction and cocaine conditioning in mice increase spontaneous spike frequency in the nucleus accumbens or septal nuclei as revealed by multielectrode array recordings.

    Science.gov (United States)

    Kummer, Kai K; El Rawas, Rana; Kress, Michaela; Saria, Alois; Zernig, Gerald

    2015-01-01

    Both cocaine and social interaction place preference conditioning lead to increased neuronal expression of the immediate early gene EGR1 in the nucleus accumbens, a central region of the reward pathway, suggesting that both drug and natural rewards may be processed in similar brain regions. In order to gain novel insights into the intrinsic in vitro electrical activity of the nucleus accumbens and adjacent brain regions and to explore the effects of reward conditioning on network activity, we performed multielectrode array recordings of spontaneous firing in acute brain slices of mice conditioned to either cocaine or social interaction place preference. Cocaine conditioning increased the spike frequency of neurons in the septal nuclei, whereas social interaction conditioning increased the spike frequency in the nucleus accumbens compared to saline control animals. In addition, social interaction conditioning decreased the amount of active neuron clusters in the nucleus accumbens. Our findings suggest that place preference conditioning for both drug and natural rewards may induce persistent changes in neuronal network activity in the nucleus accumbens and the septum that are still preserved in acute slice preparations. © 2015 S. Karger AG, Basel.

  8. Will a game cause increased fruit/vegetable intake and physical activity in elementary school children?

    OpenAIRE

    Trimble, Derek

    2017-01-01

    Background Incentives increase healthy lifestyle choices. Schools don’t have financial resources for an incentive program. Research Question Is there a way to increase fruit and vegetable intake and physical activity in elementary school children at little or no cost to the school?

  9. Lumbricus terrestris L. activity increases the availability of metals and their accumulation in maize and barley

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz, E. [Department of Chemical Engineering, School of Civil Engineering, University of Castilla-La Mancha, Avenida Camilo Jose Cela, s/n, 13071 Ciudad Real (Spain); Alonso-Azcarate, J. [Department of Physical Chemistry, Faculty of Environmental Sciences, University of Castilla-La Mancha, Avenida Carlos III, s/n, 45071 Toledo (Spain); Rodriguez, L., E-mail: Luis.Rromero@uclm.es [Department of Chemical Engineering, School of Civil Engineering, University of Castilla-La Mancha, Avenida Camilo Jose Cela, s/n, 13071 Ciudad Real (Spain)

    2011-03-15

    The effect of the earthworm Lumbricus terrestris L. on metal availability in two mining soils was assessed by means of chemical extraction methods and a pot experiment using crop plants. Results from single and sequential extractions showed that L. terrestris had a slight effect on metal fractionation in the studied soils: only metals bound to the soil organic matter were significantly increased in some cases. However, we found that L. terrestris significantly increased root, shoot and total Pb and Zn concentrations in maize and barley for the soil with the highest concentrations of total and available metals. Specifically, shoot Pb concentration was increased by a factor of 7.5 and 3.9 for maize and barley, respectively, while shoot Zn concentration was increased by a factor of 3.7 and 1.7 for maize and barley, respectively. Our results demonstrated that earthworm activity increases the bioavailability of metals in soils. - Research highlights: > Lumbricus terrestris L. activity increases the bioavailability of metals in soils. > Earthworm activity can significantly increase total, shoot and root metal concentrations for crop plants. > Both bioassays and chemical extraction methods are necessary for assessing the bioavailability of metals in contaminated soils. - Lumbricus terrestris L. activity increases the bioavailability of metals in soils and total, shoot and root metal concentrations for maize and barley.

  10. Glucocorticoid receptor number predicts increase in amygdala activity after severe stress

    NARCIS (Netherlands)

    Geuze, Elbert; van Wingen, Guido A.; van Zuiden, Mirjam; Rademaker, Arthur R.; Vermetten, Eric; Kavelaars, Annemieke; Fernández, Guillén; Heijnen, Cobi J.

    2012-01-01

    Introduction: Individuals who are exposed to a traumatic event are at increased risk of developing psychiatric disorders such as posttraumatic stress disorder (PTSD). Studies have shown that increased amygdala activity is frequently found in patients with PTSD. In addition, pre-trauma glucocorticoid

  11. Lumbricus terrestris L. activity increases the availability of metals and their accumulation in maize and barley

    International Nuclear Information System (INIS)

    Ruiz, E.; Alonso-Azcarate, J.; Rodriguez, L.

    2011-01-01

    The effect of the earthworm Lumbricus terrestris L. on metal availability in two mining soils was assessed by means of chemical extraction methods and a pot experiment using crop plants. Results from single and sequential extractions showed that L. terrestris had a slight effect on metal fractionation in the studied soils: only metals bound to the soil organic matter were significantly increased in some cases. However, we found that L. terrestris significantly increased root, shoot and total Pb and Zn concentrations in maize and barley for the soil with the highest concentrations of total and available metals. Specifically, shoot Pb concentration was increased by a factor of 7.5 and 3.9 for maize and barley, respectively, while shoot Zn concentration was increased by a factor of 3.7 and 1.7 for maize and barley, respectively. Our results demonstrated that earthworm activity increases the bioavailability of metals in soils. - Research highlights: → Lumbricus terrestris L. activity increases the bioavailability of metals in soils. → Earthworm activity can significantly increase total, shoot and root metal concentrations for crop plants. → Both bioassays and chemical extraction methods are necessary for assessing the bioavailability of metals in contaminated soils. - Lumbricus terrestris L. activity increases the bioavailability of metals in soils and total, shoot and root metal concentrations for maize and barley.

  12. Increasing Physical Activity in Preschool: A Pilot Study to Evaluate Animal Trackers

    Science.gov (United States)

    Williams, Christine L.; Carter, Betty Jean; Kibbe, Debra L.; Dennison, David

    2009-01-01

    Objective: This report describes a pilot study to evaluate Animal Trackers (AT), a preschool program designed to (1) increase structured physical activity (PA) during the preschool day; (2) increase practice of gross motor skills; (3) provide teachers with an easy-to-use PA program regardless of teacher experience; and (4) implement a teacher…

  13. Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus.

    Science.gov (United States)

    Bracey, James M; Kurz, Jonathan E; Low, Brian; Churn, Severn B

    2009-08-04

    Status epilepticus is a life-threatening form of seizure activity that represents a major medical emergency associated with significant morbidity and mortality. Protein Kinase A is an important regulator of synaptic strength that may play an important role in the development of status epilepticus-induced neuronal pathology. This study demonstrated an increase in PKA activity against exogenous and endogenous substrates during later stages of SE. As SE progressed, a significant increase in PKA-mediated phosphorylation of an exogenous peptide substrate was demonstrated in cortical structures. The increased activity was not due to altered expression of either regulatory or catalytic subunits of the enzyme. Through the use of phospho-specific antibodies, this study also investigated the effects of SE on the phosphorylation of the GluR1 subunit of the AMPA subtype of glutamate receptor. After the onset of continuous seizure activity, an increase in phosphorylation of the PKA site on the GluR1 subunit of the AMPA receptor was observed. These data suggest a potential mechanism by which SE may increase neuronal excitability in the cortex, potentially leading to maintenance of seizure activity or long-term neuronal pathology.

  14. How community environment shapes physical activity: perceptions revealed through the PhotoVoice method.

    Science.gov (United States)

    Belon, Ana Paula; Nieuwendyk, Laura M; Vallianatos, Helen; Nykiforuk, Candace I J

    2014-09-01

    A growing body of evidence shows that community environment plays an important role in individuals' physical activity engagement. However, while attributes of the physical environment are widely investigated, sociocultural, political, and economic aspects of the environment are often neglected. This article helps to fill these knowledge gaps by providing a more comprehensive understanding of multiple dimensions of the community environment relative to physical activity. The purpose of this study was to qualitatively explore how people's experiences and perceptions of their community environments affect their abilities to engage in physical activity. A PhotoVoice method was used to identify barriers to and opportunities for physical activity among residents in four communities in the province of Alberta, Canada, in 2009. After taking pictures, the thirty-five participants shared their perceptions of those opportunities and barriers in their community environments during individual interviews. Using the Analysis Grid for Environments Linked to Obesity (ANGELO) framework, themes emerging from these photo-elicited interviews were organized in four environment types: physical, sociocultural, economic, and political. The data show that themes linked to the physical (56.6%) and sociocultural (31.4%) environments were discussed more frequently than the themes of the economic (5.9%) and political (6.1%) environments. Participants identified nuanced barriers and opportunities for physical activity, which are illustrated by their quotes and photographs. The findings suggest that a myriad of factors from physical, sociocultural, economic, and political environments influence people's abilities to be physically active in their communities. Therefore, adoption of a broad, ecological perspective is needed to address the barriers and build upon the opportunities described by participants to make communities more healthy and active. Copyright © 2014 Elsevier Ltd. All rights

  15. From Blame to Punishment: Disrupting Prefrontal Cortex Activity Reveals Norm Enforcement Mechanisms.

    Science.gov (United States)

    Buckholtz, Joshua W; Martin, Justin W; Treadway, Michael T; Jan, Katherine; Zald, David H; Jones, Owen; Marois, René

    2015-09-23

    The social welfare provided by cooperation depends on the enforcement of social norms. Determining blameworthiness and assigning a deserved punishment are two cognitive cornerstones of norm enforcement. Although prior work has implicated the dorsolateral prefrontal cortex (DLPFC) in norm-based judgments, the relative contribution of this region to blameworthiness and punishment decisions remains poorly understood. Here, we used repetitive transcranial magnetic stimulation (rTMS) and fMRI to determine the specific role of DLPFC function in norm-enforcement behavior. DLPFC rTMS reduced punishment for wrongful acts without affecting blameworthiness ratings, and fMRI revealed punishment-selective DLPFC recruitment, suggesting that these two facets of norm-based decision making are neurobiologically dissociable. Finally, we show that DLPFC rTMS affects punishment decision making by altering the integration of information about culpability and harm. Together, these findings reveal a selective, causal role for DLPFC in norm enforcement: representational integration of the distinct information streams used to make punishment decisions. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Genetically encoded proton sensors reveal activity-dependent pH changes in neurons

    Directory of Open Access Journals (Sweden)

    Joseph Valentino Raimondo

    2012-05-01

    Full Text Available The regulation of hydrogen ion concentration (pH is fundamental to cell viability, metabolism and enzymatic function. Within the nervous system, the control of pH is also involved in diverse and dynamic processes including development, synaptic transmission and the control of network excitability. As pH affects neuronal activity, and can also itself be altered by neuronal activity, the existence of tools to accurately measure hydrogen ion fluctuations is important for understanding the role pH plays under physiological and pathological conditions. Outside of their use as a marker of synaptic release, genetically encoded pH sensors have not been utilised to study hydrogen ion fluxes associated with network activity. By combining whole-cell patch clamp with simultaneous two-photon or confocal imaging, we quantified the amplitude and time course of neuronal, intracellular, acidic transients evoked by epileptiform activity in two separate in vitro models of temporal lobe epilepsy. In doing so, we demonstrate the suitability of three genetically encoded pH sensors: deGFP4, E2GFP and Cl-sensor for investigating activity-dependent pH changes at the level of single neurons.

  17. Genetically encoded proton sensors reveal activity-dependent pH changes in neurons.

    Science.gov (United States)

    Raimondo, Joseph V; Irkle, Agnese; Wefelmeyer, Winnie; Newey, Sarah E; Akerman, Colin J

    2012-01-01

    The regulation of hydrogen ion concentration (pH) is fundamental to cell viability, metabolism, and enzymatic function. Within the nervous system, the control of pH is also involved in diverse and dynamic processes including development, synaptic transmission, and the control of network excitability. As pH affects neuronal activity, and can also itself be altered by neuronal activity, the existence of tools to accurately measure hydrogen ion fluctuations is important for understanding the role pH plays under physiological and pathological conditions. Outside of their use as a marker of synaptic release, genetically encoded pH sensors have not been utilized to study hydrogen ion fluxes associated with network activity. By combining whole-cell patch clamp with simultaneous two-photon or confocal imaging, we quantified the amplitude and time course of neuronal, intracellular, acidic transients evoked by epileptiform activity in two separate in vitro models of temporal lobe epilepsy. In doing so, we demonstrate the suitability of three genetically encoded pH sensors: deGFP4, E(2)GFP, and Cl-sensor for investigating activity-dependent pH changes at the level of single neurons.

  18. Potential to increase active commuting level in university area (Case study: Universitas Gadjah Mada)

    Science.gov (United States)

    Devi, M. K.

    2017-06-01

    In order to alleviate the negative impacts of motorized vehicle use as well as create sustainable environment within campus area, it is pivotal to encourage mode shifting among university students. Active transport modes such as walking, cycling, and using public transport can be considered as alternative modes. This paper tried to identify the potential to increase active commuting in UGM by understanding student’s travel behavior. ANOVA test was employed to identify the perceptions between students across residential zones toward motivators and barriers to actively commute. The findings were used to propose strategies for increasing active commuting level in UGM, which are: reducing barriers to actively commute, improving public transport services, improving walking and cycling facilities, and introducing programs to discourage motorized vehicle use.

  19. Mutational and structural analyses of Caldanaerobius polysaccharolyticus Man5B reveal novel active site residues for family 5 glycoside hydrolases.

    Science.gov (United States)

    Oyama, Takuji; Schmitz, George E; Dodd, Dylan; Han, Yejun; Burnett, Alanna; Nagasawa, Naoko; Mackie, Roderick I; Nakamura, Haruki; Morikawa, Kosuke; Cann, Isaac

    2013-01-01

    CpMan5B is a glycoside hydrolase (GH) family 5 enzyme exhibiting both β-1,4-mannosidic and β-1,4-glucosidic cleavage activities. To provide insight into the amino acid residues that contribute to catalysis and substrate specificity, we solved the structure of CpMan5B at 1.6 Å resolution. The structure revealed several active site residues (Y12, N92 and R196) in CpMan5B that are not present in the active sites of other structurally resolved GH5 enzymes. Residue R196 in GH5 enzymes is thought to be strictly conserved as a histidine that participates in an electron relay network with the catalytic glutamates, but we show that an arginine fulfills a functionally equivalent role and is found at this position in every enzyme in subfamily GH5_36, which includes CpMan5B. Residue N92 is required for full enzymatic activity and forms a novel bridge over the active site that is absent in other family 5 structures. Our data also reveal a role of Y12 in establishing the substrate preference for CpMan5B. Using these molecular determinants as a probe allowed us to identify Man5D from Caldicellulosiruptor bescii as a mannanase with minor endo-glucanase activity.

  20. Mutational and structural analyses of Caldanaerobius polysaccharolyticus Man5B reveal novel active site residues for family 5 glycoside hydrolases.

    Directory of Open Access Journals (Sweden)

    Takuji Oyama

    Full Text Available CpMan5B is a glycoside hydrolase (GH family 5 enzyme exhibiting both β-1,4-mannosidic and β-1,4-glucosidic cleavage activities. To provide insight into the amino acid residues that contribute to catalysis and substrate specificity, we solved the structure of CpMan5B at 1.6 Å resolution. The structure revealed several active site residues (Y12, N92 and R196 in CpMan5B that are not present in the active sites of other structurally resolved GH5 enzymes. Residue R196 in GH5 enzymes is thought to be strictly conserved as a histidine that participates in an electron relay network with the catalytic glutamates, but we show that an arginine fulfills a functionally equivalent role and is found at this position in every enzyme in subfamily GH5_36, which includes CpMan5B. Residue N92 is required for full enzymatic activity and forms a novel bridge over the active site that is absent in other family 5 structures. Our data also reveal a role of Y12 in establishing the substrate preference for CpMan5B. Using these molecular determinants as a probe allowed us to identify Man5D from Caldicellulosiruptor bescii as a mannanase with minor endo-glucanase activity.

  1. Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium

    Energy Technology Data Exchange (ETDEWEB)

    Wernimont, Amy K; Artz, Jennifer D.; Jr, Patrick Finerty; Lin, Yu-Hui; Amani, Mehrnaz; Allali-Hassani, Abdellah; Senisterra, Guillermo; Vedadi, Masoud; Tempel, Wolfram; Mackenzie, Farrell; Chau, Irene; Lourido, Sebastian; Sibley, L. David; Hui, Raymond (Toronto); (WU-MED)

    2010-09-21

    Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium binding triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.

  2. Structure of TSA2 reveals novel features of the active-site loop of peroxiredoxins

    DEFF Research Database (Denmark)

    Nielsen, Maja Holch; Kidmose, Rune Thomas; Jenner, Lasse Bohl

    2016-01-01

    Saccharomyces cerevisiae TSA2 belongs to the family of typical 2-Cys peroxiredoxins, a ubiquitously expressed family of redox-active enzymes that utilize a conserved peroxidatic cysteine to reduce peroxides. Typical 2-Cys peroxiredoxins have been shown to be involved in protection against oxidative...... stress and in hydrogen peroxide signalling. Furthermore, several 2-Cys peroxiredoxins, including S. cerevisiae TSA1 and TSA2, are able to switch to chaperone activity upon hyperoxidation of their peroxidatic cysteine. This makes the sensitivity to hyperoxidation of the peroxidatic cysteine a very....... This requires a local unfolding of the active site and the C-terminus. The balance between the fully folded and locally unfolded conformations is of key importance for the reactivity and sensitivity to hyperoxidation of the different peroxiredoxins. Here, the structure of a C48S mutant of TSA2 from S...

  3. Evaluation of a faculty development program aimed at increasing residents' active learning in lectures.

    Science.gov (United States)

    Desselle, Bonnie C; English, Robin; Hescock, George; Hauser, Andrea; Roy, Melissa; Yang, Tong; Chauvin, Sheila W

    2012-12-01

    Active engagement in the learning process is important to enhance learners' knowledge acquisition and retention and the development of their thinking skills. This study evaluated whether a 1-hour faculty development workshop increased the use of active teaching strategies and enhanced residents' active learning and thinking. Faculty teaching in a pediatrics residency participated in a 1-hour workshop (intervention) approximately 1 month before a scheduled lecture. Participants' responses to a preworkshop/postworkshop questionnaire targeted self-efficacy (confidence) for facilitating active learning and thinking and providing feedback about workshop quality. Trained observers assessed each lecture (3-month baseline phase and 3-month intervention phase) using an 8-item scale for use of active learning strategies and a 7-item scale for residents' engagement in active learning. Observers also assessed lecturer-resident interactions and the extent to which residents were asked to justify their answers. Responses to the workshop questionnaire (n  =  32/34; 94%) demonstrated effectiveness and increased confidence. Faculty in the intervention phase demonstrated increased use of interactive teaching strategies for 6 items, with 5 reaching statistical significance (P ≤ .01). Residents' active learning behaviors in lectures were higher in the intervention arm for all 7 items, with 5 reaching statistical significance. Faculty in the intervention group demonstrated increased use of higher-order questioning (P  =  .02) and solicited justifications for answers (P  =  .01). A 1-hour faculty development program increased faculty use of active learning strategies and residents' engagement in active learning during resident core curriculum lectures.

  4. Clofibrate-induced increases in peroxisomal proteins: effect on synthesis, degradation, and mRNA activity

    International Nuclear Information System (INIS)

    Mortensen, R.M.

    1983-01-01

    The effect of clofibrate on the polypeptide composition of peroxisomes was determined. A simple method was developed for the isolation of peroxisomes with a purity of 90-95% using sedimentation in a metrizamide gradient. The specific activities of HD did not change with clofibrate treatment so that the increases in enzyme activities are solely due to increases in protein amounts. The hepatic concentration of HD increased 63 times. The HD synthesis rate, as measured by the incorporation of [ 3 H]leucine, increased 74 times, so that the increase in the synthesis was sufficient to account for the increase in protein. Clofibrate caused no discernible change in the degradation rate of HD labeled with [ 14 C]bicarbonate. The half-life of HD was approximately 2 days. The translatable mRBA coding for HD increased 55 times. This value is not significantly different from the increase in HD protein or in HD synthesis. This observation was also true for several other peroxisomal proteins. Therefore, clofibrate causes an increase in the mRNA activity, which increases the synthesis of HD leading to an accumulation of protein and enzyme activity. The kinetics of the clofibrate-induced changes in HD synthesis rate, protein level, and enzymatic activity was analyzed using a simple model which included the half-lives of the drug, mRNA, and protein. The best fit of the model to the data gave an mRNA half-life of 10 hours and a protein half-life of 1.8 days, with no significant change by clofibrate

  5. Alpha-Band Activity Reveals Spontaneous Representations of Spatial Position in Visual Working Memory.

    Science.gov (United States)

    Foster, Joshua J; Bsales, Emma M; Jaffe, Russell J; Awh, Edward

    2017-10-23

    An emerging view suggests that spatial position is an integral component of working memory (WM), such that non-spatial features are bound to locations regardless of whether space is relevant [1, 2]. For instance, past work has shown that stimulus position is spontaneously remembered when non-spatial features are stored. Item recognition is enhanced when memoranda appear at the same location where they were encoded [3-5], and accessing non-spatial information elicits shifts of spatial attention to the original position of the stimulus [6, 7]. However, these findings do not establish that a persistent, active representation of stimulus position is maintained in WM because similar effects have also been documented following storage in long-term memory [8, 9]. Here we show that the spatial position of the memorandum is actively coded by persistent neural activity during a non-spatial WM task. We used a spatial encoding model in conjunction with electroencephalogram (EEG) measurements of oscillatory alpha-band (8-12 Hz) activity to track active representations of spatial position. The position of the stimulus varied trial to trial but was wholly irrelevant to the tasks. We nevertheless observed active neural representations of the original stimulus position that persisted throughout the retention interval. Further experiments established that these spatial representations are dependent on the volitional storage of non-spatial features rather than being a lingering effect of sensory energy or initial encoding demands. These findings provide strong evidence that online spatial representations are spontaneously maintained in WM-regardless of task relevance-during the storage of non-spatial features. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats.

    Science.gov (United States)

    Tong, Wenni; Chen, Wanqiu; Ostrowski, Robert P; Ma, Qingyi; Souvenir, Rhonda; Zhang, Lubo; Zhang, John H; Tang, Jiping

    2010-02-15

    A recent study has shown that increased activity of matrix metalloproteinases-2 and metalloproteinases-9 (MMP-2 and MMP-9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP-2 and MMP-9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP-2 and MMP-9 and the protein abundance of TIMP-1 and TIMP-2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP-2 at day 0, and increased MMP-9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP-2, MMP-9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals.

  7. Determination of the physiological 2:2 TLR5:flagellin activation stoichiometry revealed by the activity of a fusion receptor

    International Nuclear Information System (INIS)

    Ivičak-Kocjan, Karolina; Panter, Gabriela; Benčina, Mojca; Jerala, Roman

    2013-01-01

    Highlights: •The chimeric protein fusing flagellin to the TLR5 ectodomain is constitutively active. •Mutation P736H within the BB-loop of TLR5 TIR domain renders the receptor inactive. •The R90D mutation in flagellin inactivated autoactivation of the chimeric protein. •The 2:2 stoichiometry of the TLR5:flagellin complex is physiologically relevant. -- Abstract: Toll-like receptor 5 (TLR5) recognizes flagellin of most flagellated bacteria, enabling activation of the MyD88-dependent signaling pathway. The recently published crystal structure of a truncated zebrafish TLR5 ectodomain in complex with an inactive flagellin fragment indicated binding of two flagellin molecules to a TLR5 homodimer, however this complex did not dimerize in solution. In the present study, we aimed to determine the physiological stoichiometry of TLR5:flagellin activation by the use of a chimeric protein composed of an active flagellin fragment linked to the N-terminus of human TLR5 (SF-TLR5). This construct was constitutively active. Inactivation by the R90D mutation within flagellin demonstrated that autoactivation of the chimeric protein depended solely on the specific interaction between TLR5 and flagellin. Addition of wild-type hTLR5 substantially lowered autoactivation of SF-TLR5 in a concentration dependent manner, an effect which was reversible by the addition of exogenous Salmonella typhimurium flagellin, indicating the biological activity of a TLR5:flagellin complex with a 2:2 stoichiometry. These results, in addition to the combinations of inactive P736H mutation within the BB-loop of the TIR domain of TLR5 and SF-TLR5, further confirm the mechanism of TLR5 activation

  8. Determination of the physiological 2:2 TLR5:flagellin activation stoichiometry revealed by the activity of a fusion receptor

    Energy Technology Data Exchange (ETDEWEB)

    Ivičak-Kocjan, Karolina; Panter, Gabriela; Benčina, Mojca [Laboratory of Biotechnology, National Institute of Chemistry, 1000 Ljubljana (Slovenia); The Centre of Excellence EN-FIST, 1000 Ljubljana (Slovenia); Jerala, Roman, E-mail: roman.jerala@ki.si [Laboratory of Biotechnology, National Institute of Chemistry, 1000 Ljubljana (Slovenia); The Centre of Excellence EN-FIST, 1000 Ljubljana (Slovenia); The Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana (Slovenia)

    2013-05-24

    Highlights: •The chimeric protein fusing flagellin to the TLR5 ectodomain is constitutively active. •Mutation P736H within the BB-loop of TLR5 TIR domain renders the receptor inactive. •The R90D mutation in flagellin inactivated autoactivation of the chimeric protein. •The 2:2 stoichiometry of the TLR5:flagellin complex is physiologically relevant. -- Abstract: Toll-like receptor 5 (TLR5) recognizes flagellin of most flagellated bacteria, enabling activation of the MyD88-dependent signaling pathway. The recently published crystal structure of a truncated zebrafish TLR5 ectodomain in complex with an inactive flagellin fragment indicated binding of two flagellin molecules to a TLR5 homodimer, however this complex did not dimerize in solution. In the present study, we aimed to determine the physiological stoichiometry of TLR5:flagellin activation by the use of a chimeric protein composed of an active flagellin fragment linked to the N-terminus of human TLR5 (SF-TLR5). This construct was constitutively active. Inactivation by the R90D mutation within flagellin demonstrated that autoactivation of the chimeric protein depended solely on the specific interaction between TLR5 and flagellin. Addition of wild-type hTLR5 substantially lowered autoactivation of SF-TLR5 in a concentration dependent manner, an effect which was reversible by the addition of exogenous Salmonella typhimurium flagellin, indicating the biological activity of a TLR5:flagellin complex with a 2:2 stoichiometry. These results, in addition to the combinations of inactive P736H mutation within the BB-loop of the TIR domain of TLR5 and SF-TLR5, further confirm the mechanism of TLR5 activation.

  9. Large-scale transcriptome data reveals transcriptional activity of fission yeast LTR retrotransposons

    DEFF Research Database (Denmark)

    Mourier, Tobias; Willerslev, Eske

    2010-01-01

    of transcriptional activity are observed from both strands of solitary LTR sequences. Transcriptome data collected during meiosis suggests that transcription of solitary LTRs is correlated with the transcription of nearby protein-coding genes. CONCLUSIONS: Presumably, the host organism negatively regulates...

  10. Correlations between human mobility and social interaction reveal general activity patterns

    DEFF Research Database (Denmark)

    Mollgaard, Anders; Jørgensen, Sune Lehmann; Mathiesen, Joachim

    2017-01-01

    A day in the life of a person involves a broad range of activities which are common across many people. Going beyond diurnal cycles, a central question is: to what extent do individuals act according to patterns shared across an entire population? Here we investigate the interplay between differe...... they be of social or of physical character....

  11. Xenobiotics and the Human Gut Microbiome: Metatranscriptomics Reveal the Active Players

    OpenAIRE

    Ursell, Luke K.; Knight, Rob

    2013-01-01

    The human gut microbiome plays an important role in the metabolism of xenobiotics. In a recent issue of Cell, Maurice et al. identify the active members of the gut microbiome and show how gene expression profiles change within the gut microbial community in response to antibiotics and host-targeted xenobiotics.

  12. Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells

    Science.gov (United States)

    Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in “BPA-free” products. We have compared estrogeni...

  13. Toll-like receptor activation reveals developmental reorganization and unmasks responder subsets of microglia

    NARCIS (Netherlands)

    Scheffel, Joerg; Regen, Tommy; Van Rossum, Denise; Seifert, Stefanie; Ribes, Sandra; Nau, Roland; Parsa, Roham; Harris, Robert A.; Boddeke, Hendrikus W. G. M.; Chuang, Han-Ning; Pukrop, Tobias; Wessels, Johannes T.; Juergens, Tanja; Merkler, Doron; Brueck, Wolfgang; Schnaars, Mareike; Simons, Mikael; Kettenmann, Helmut; Hanisch, Uwe-Karsten

    2012-01-01

    The sentinel and immune functions of microglia require rapid and appropriate reactions to infection and damage. Their Toll-like receptors (TLRs) sense both as threats. However, whether activated microglia mount uniform responses or whether subsets conduct selective tasks is unknown. We demonstrate

  14. Functional and evolutionary characterization of Ohr proteins in eukaryotes reveals many active homologs among pathogenic fungi

    Directory of Open Access Journals (Sweden)

    D.A. Meireles

    2017-08-01

    Full Text Available Ohr and OsmC proteins comprise two subfamilies within a large group of proteins that display Cys-based, thiol dependent peroxidase activity. These proteins were previously thought to be restricted to prokaryotes, but we show here, using iterated sequence searches, that Ohr/OsmC homologs are also present in 217 species of eukaryotes with a massive presence in Fungi (186 species. Many of these eukaryotic Ohr proteins possess an N-terminal extension that is predicted to target them to mitochondria. We obtained recombinant proteins for four eukaryotic members of the Ohr/OsmC family and three of them displayed lipoyl peroxidase activity. Further functional and biochemical characterization of the Ohr homologs from the ascomycete fungus Mycosphaerella fijiensis Mf_1 (MfOhr, the causative agent of Black Sigatoka disease in banana plants, was pursued. Similarly to what has been observed for the bacterial proteins, we found that: (i the peroxidase activity of MfOhr was supported by DTT or dihydrolipoamide (dithiols, but not by β-mercaptoethanol or GSH (monothiols, even in large excess; (ii MfOhr displayed preference for organic hydroperoxides (CuOOH and tBOOH over hydrogen peroxide; (iii MfOhr presented extraordinary reactivity towards linoleic acid hydroperoxides (k=3.18 (±2.13×108 M−1 s−1. Both Cys87 and Cys154 were essential to the peroxidase activity, since single mutants for each Cys residue presented no activity and no formation of intramolecular disulfide bond upon treatment with hydroperoxides. The pKa value of the Cysp residue was determined as 5.7±0.1 by a monobromobimane alkylation method. Therefore, eukaryotic Ohr peroxidases share several biochemical features with prokaryotic orthologues and are preferentially located in mitochondria. Keywords: Ohr/OsmC, Thiol-dependent peroxidases, Phylogeny

  15. Functional and evolutionary characterization of Ohr proteins in eukaryotes reveals many active homologs among pathogenic fungi.

    Science.gov (United States)

    Meireles, D A; Domingos, R M; Gaiarsa, J W; Ragnoni, E G; Bannitz-Fernandes, R; da Silva Neto, J F; de Souza, R F; Netto, L E S

    2017-08-01

    Ohr and OsmC proteins comprise two subfamilies within a large group of proteins that display Cys-based, thiol dependent peroxidase activity. These proteins were previously thought to be restricted to prokaryotes, but we show here, using iterated sequence searches, that Ohr/OsmC homologs are also present in 217 species of eukaryotes with a massive presence in Fungi (186 species). Many of these eukaryotic Ohr proteins possess an N-terminal extension that is predicted to target them to mitochondria. We obtained recombinant proteins for four eukaryotic members of the Ohr/OsmC family and three of them displayed lipoyl peroxidase activity. Further functional and biochemical characterization of the Ohr homologs from the ascomycete fungus Mycosphaerella fijiensis Mf_1 (MfOhr), the causative agent of Black Sigatoka disease in banana plants, was pursued. Similarly to what has been observed for the bacterial proteins, we found that: (i) the peroxidase activity of MfOhr was supported by DTT or dihydrolipoamide (dithiols), but not by β-mercaptoethanol or GSH (monothiols), even in large excess; (ii) MfOhr displayed preference for organic hydroperoxides (CuOOH and tBOOH) over hydrogen peroxide; (iii) MfOhr presented extraordinary reactivity towards linoleic acid hydroperoxides (k=3.18 (±2.13)×10 8 M -1 s -1 ). Both Cys 87 and Cys 154 were essential to the peroxidase activity, since single mutants for each Cys residue presented no activity and no formation of intramolecular disulfide bond upon treatment with hydroperoxides. The pK a value of the Cys p residue was determined as 5.7±0.1 by a monobromobimane alkylation method. Therefore, eukaryotic Ohr peroxidases share several biochemical features with prokaryotic orthologues and are preferentially located in mitochondria. Copyright © 2017. Published by Elsevier B.V.

  16. The spatiotemporal pattern of Src activation at lipid rafts revealed by diffusion-corrected FRET imaging.

    Directory of Open Access Journals (Sweden)

    Shaoying Lu

    2008-07-01

    Full Text Available Genetically encoded biosensors based on fluorescence resonance energy transfer (FRET have been widely applied to visualize the molecular activity in live cells with high spatiotemporal resolution. However, the rapid diffusion of biosensor proteins hinders a precise reconstruction of the actual molecular activation map. Based on fluorescence recovery after photobleaching (FRAP experiments, we have developed a finite element (FE method to analyze, simulate, and subtract the diffusion effect of mobile biosensors. This method has been applied to analyze the mobility of Src FRET biosensors engineered to reside at different subcompartments in live cells. The results indicate that the Src biosensor located in the cytoplasm moves 4-8 folds faster (0.93+/-0.06 microm(2/sec than those anchored on different compartments in plasma membrane (at lipid raft: 0.11+/-0.01 microm(2/sec and outside: 0.18+/-0.02 microm(2/sec. The mobility of biosensor at lipid rafts is slower than that outside of lipid rafts and is dominated by two-dimensional diffusion. When this diffusion effect was subtracted from the FRET ratio images, high Src activity at lipid rafts was observed at clustered regions proximal to the cell periphery, which remained relatively stationary upon epidermal growth factor (EGF stimulation. This result suggests that EGF induced a Src activation at lipid rafts with well-coordinated spatiotemporal patterns. Our FE-based method also provides an integrated platform of image analysis for studying molecular mobility and reconstructing the spatiotemporal activation maps of signaling molecules in live cells.

  17. Quantitative Proteomics Reveals Temporal Proteomic Changes in Signaling Pathways during BV2 Mouse Microglial Cell Activation.

    Science.gov (United States)

    Woo, Jongmin; Han, Dohyun; Wang, Joseph Injae; Park, Joonho; Kim, Hyunsoo; Kim, Youngsoo

    2017-09-01

    The development of systematic proteomic quantification techniques in systems biology research has enabled one to perform an in-depth analysis of cellular systems. We have developed a systematic proteomic approach that encompasses the spectrum from global to targeted analysis on a single platform. We have applied this technique to an activated microglia cell system to examine changes in the intracellular and extracellular proteomes. Microglia become activated when their homeostatic microenvironment is disrupted. There are varying degrees of microglial activation, and we chose to focus on the proinflammatory reactive state that is induced by exposure to such stimuli as lipopolysaccharide (LPS) and interferon-gamma (IFN-γ). Using an improved shotgun proteomics approach, we identified 5497 proteins in the whole-cell proteome and 4938 proteins in the secretome that were associated with the activation of BV2 mouse microglia by LPS or IFN-γ. Of the differentially expressed proteins in stimulated microglia, we classified pathways that were related to immune-inflammatory responses and metabolism. Our label-free parallel reaction monitoring (PRM) approach made it possible to comprehensively measure the hyper-multiplex quantitative value of each protein by high-resolution mass spectrometry. Over 450 peptides that corresponded to pathway proteins and direct or indirect interactors via the STRING database were quantified by label-free PRM in a single run. Moreover, we performed a longitudinal quantification of secreted proteins during microglial activation, in which neurotoxic molecules that mediate neuronal cell loss in the brain are released. These data suggest that latent pathways that are associated with neurodegenerative diseases can be discovered by constructing and analyzing a pathway network model of proteins. Furthermore, this systematic quantification platform has tremendous potential for applications in large-scale targeted analyses. The proteomics data for

  18. Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors.

    Science.gov (United States)

    Wang, Lei; de Kloet, Annette D; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A; Pioquinto, David J; Ludin, Jacob A; Oh, S Paul; Katovich, Michael J; Frazier, Charles J; Raizada, Mohan K; Krause, Eric G

    2016-06-01

    Over-activation of the brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme 2 (ACE2) inhibits RAS activity by converting angiotensin-II, the effector peptide of RAS, to angiotensin-(1-7), which activates the Mas receptor (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ∼62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the

  19. Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer's disease.

    LENUS (Irish Health Repository)

    Ewers, Michael

    2012-02-01

    The enzyme beta-secretase (BACE1) is essentially involved in the production of cerebral amyloidogenic pathology in Alzheimer\\'s disease (AD). The measurement of BACE1 activity in cerebrospinal fluid (CSF) has been reported, which may render CSF measurement of BACE1 a potential biomarker candidate of AD. In order to investigate whether BACE1 protein activity is correlated with regional brain atrophy in AD, we investigated the association between CSF levels of BACE1 and MRI-assessed hippocampus volume in patients with AD (n = 30). An increase in CSF-BACE1 activity was associated with decreased left and right hippocampus volume corrected for global head volume in the AD patients. Boot-strapped regression analysis showed that increased CSF levels of BACE1 activity were associated with increased CSF concentration of total tau but not amyloid-beta1-42 in AD. White matter hyperintensities did not influence the results. BACE1 activity and protein levels were significantly increased in AD compared to 19 elderly healthy controls. Thus, the CSF biomarker candidate of BACE1 activity was associated with hippocampus atrophy in AD in a robust manner and may reflect neurotoxic amyloid-beta-related processes.

  20. Shale gas activity and increased rates of sexually transmitted infections in Ohio, 2000-2016.

    Directory of Open Access Journals (Sweden)

    Nicole C Deziel

    Full Text Available The growing shale gas ("fracking" industry depends on a mobile workforce, whose influx could have social impacts on host communities. Sexually transmitted infections (STIs can increase through sexual mixing patterns associated with labor migration. No prior studies have quantified the relationship between shale gas activity and rates of three reportable STIs: chlamydia, gonorrhea, and syphilis.We conducted a longitudinal, ecologic study from 2000-2016 in Ohio, situated in a prolific shale gas region in the United States (US. Data on reported cases of chlamydia, gonorrhea, and syphilis by county and year were obtained from the Ohio Department of Health. All 88 counties were classified as none, low, and high shale gas activity in each year, using data from the Ohio Department of Natural Resources. Annual rate ratios (RR and 95% confidence intervals (95% CIs were calculated from mixed-effects Poisson regression models evaluating the relationship between shale gas activity and reported annual STI rates while adjusting for secular trends and potential confounders obtained from the US Census.Compared to counties with no shale gas activity, counties with high activity had 21% (RR = 1.21; 95%CI = 1.08-1.36 increased rates of chlamydia and 19% (RR = 1.27; 95%CI 0.98-1.44 increased rates of gonorrhea, respectively. No association was observed for syphilis.This first report of a link between shale gas activity and increased rates of both chlamydia and gonorrhea may inform local policies and community health efforts.

  1. Estrogen increases Nrf2 activity through activation of the PI3K pathway in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Juanjuan, E-mail: jwu32@emory.edu [Department of Gynecology and Obstetrics, Emory University School of Medicine, 101 Woodruff Circle, Suite 4211 WMB, Atlanta, GA 30322 (United States); Williams, Devin [Department of Obstetrics and Gynecology, Morehouse School of Medicine, Atlanta, GA 30310 (United States); Walter, Grant A. [Department of Gynecology and Obstetrics, Emory University School of Medicine, 101 Woodruff Circle, Suite 4211 WMB, Atlanta, GA 30322 (United States); Thompson, Winston E. [Department of Obstetrics and Gynecology, Morehouse School of Medicine, Atlanta, GA 30310 (United States); Sidell, Neil [Department of Gynecology and Obstetrics, Emory University School of Medicine, 101 Woodruff Circle, Suite 4211 WMB, Atlanta, GA 30322 (United States)

    2014-11-01

    The actions of the transcription factor Nuclear factor erythroid 2-related factor (Nrf2) in breast cancer have been shown to include both pro-oncogenic and anti-oncogenic activities which is influenced, at least in part, by the hormonal environment. However, direct regulation of Nrf2 by steroid hormones (estrogen and progesterone) has received only scant attention. Nrf2 is known to be regulated by its cytosolic binding protein, Kelch-like ECH-associated protein 1 (Keap1), and by a Keap1-independent mechanism involving a series of phosphorylation steps mediated by phosphatidylinositol 3-kinase (PI3K) and glycogen synthase kinase 3 beta (GSK3β). Here, we report that estrogen (E2) increases Nrf2 activity in MCF7 breast cancer cells through activation of the PI3K/GSK3β pathway. Utilizing antioxidant response element (ARE)-containing luciferase reporter constructs as read-outs for Nrf2 activity, our data indicated that E2 increased ARE activity >14-fold and enhanced the action of the Nrf2 activators, tertiary butylhydroquinone (tBHQ) and sulforaphane (Sul) 4 to 9 fold compared with cells treated with tBHQ or Sul as single agents. This activity was shown to be an estrogen receptor-mediated phenomenon and was antagonized by progesterone. In addition to its action on the reporter constructs, mRNA and protein levels of heme oxygenase 1, an endogenous target gene of Nrf2, was markedly upregulated by E2 both alone and in combination with tBHQ. Importantly, E2-induced Nrf2 activation was completely suppressed by the PI3K inhibitors LY294002 and Wortmannin while the GSK3β inhibitor CT99021 upregulated Nrf2 activity. Confirmation that E2 was, at least partly, acting through the PI3K/GSK3β pathway was indicated by our finding that E2 increased the phosphorylation status of both GSK3β and Akt, a well-characterized downstream target of PI3K. Together, these results demonstrate a novel mechanism by which E2 can regulate Nrf2 activity in estrogen receptor-positive breast cancer

  2. Increase in posterior alpha activity during rehearsal predicts successful long-term memory formation of word sequences.

    Science.gov (United States)

    Meeuwissen, Esther B; Takashima, Atsuko; Fernández, Guillén; Jensen, Ole

    2011-12-01

    It is becoming increasingly clear that demanding cognitive tasks rely on an extended network engaging task-relevant areas and, importantly, disengaging task-irrelevant areas. Given that alpha activity (8-12 Hz) has been shown to reflect the disengagement of task-irrelevant regions in attention and working memory tasks, we here ask if alpha activity plays a related role for long-term memory formation. Subjects were instructed to encode and maintain the order of word sequences while the ongoing brain activity was recorded using magnetoencephalography (MEG). In each trial, three words were presented followed by a 3.4 s rehearsal interval. Considering the good temporal resolution of MEG this allowed us to investigate the word presentation and rehearsal interval separately. The sequences were grouped in trials where word order either could be tested immediately (working memory trials; WM) or later (LTM trials) according to instructions. Subjects were tested on their ability to retrieve the order of the three words. The data revealed that alpha power in parieto-occipital regions was lower during word presentation compared to rehearsal. Our key finding was that parieto-occipital alpha power during the rehearsal period was markedly stronger for successfully than unsuccessfully encoded LTM sequences. This subsequent memory effect demonstrates that high posterior alpha activity creates an optimal brain state for successful LTM formation possibly by actively reducing parieto-occipital activity that might interfere with sequence encoding. Copyright © 2010 Wiley Periodicals, Inc.

  3. Increased p21ras activity in human fibroblasts transduced with survivin enhances cell proliferation

    International Nuclear Information System (INIS)

    Temme, Achim; Diestelkoetter-Bachert, Petra; Schmitz, Marc; Morgenroth, Agnieszka; Weigle, Bernd; Rieger, Michael A.; Kiessling, Andrea; Rieber, E. Peter

    2005-01-01

    Survivin is critically involved in mitosis and when overexpressed enhances the activity of the Aurora B kinase, a serine-threonine kinase belonging to the family of oncogenic Aurora/IpI1p-related kinases. Both proteins interact with Ras GTPase-activating protein suggesting an impact on the Ras pathway. This study aimed at defining the role of survivin in proliferation and potential transformation of cells. When survivin was overexpressed in normal human lung fibroblasts, the characteristic track lanes of fibroblasts were disturbed and the rate of cell proliferation was increased. An enhanced level of p21 ras mRNA and protein expression and concomitant rise in levels of activated p21 ras were observed. Despite increased proliferation cell survival remained dependent on serum and cells were not able to form colonies in soft agar assays. These data suggest that overexpression of survivin increases cell growth but, despite the increase in active p21 ras , is not sufficient to transform primary cells. Yet, in addition to its anti-apoptotic function it might contribute to the accelerated growth of tumour cells by increasing p21 ras activity

  4. Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance

    International Nuclear Information System (INIS)

    Beckman, J.S.; Minor, R.L. Jr.; White, C.W.; Repine, J.E.; Rosen, G.M.; Freeman, B.A.

    1988-01-01

    Covalent conjugation of superoxide dismutase and catalase with polyethylene glycol (PEG) increases the circulatory half-lives of these enzymes from 125 I-PEG-catalase or 125 I-PEG-superoxide dismutase produced a linear, concentration-dependent increase in cellular enzyme activity and radioactivity. Fluorescently labeled PEG-superoxide dismutase incubated with endothelial cells showed a vesicular localization. Mechanical injury to cell monolayers, which is known to stimulate endocytosis, further increased the uptake of fluorescent PEG-superoxide dismutase. Addition of PEG and PEG-conjugated enzymes perturbed the spin-label binding environment, indicative of producing an increase in plasma membrane fluidity. Thus, PEG conjugation to superoxide dismutase and catalase enhances cell association of these enzymes in a manner which increases cellular enzyme activities and provides prolonged protection from partially reduced oxygen species

  5. Uncoupling of dynamin polymerization and GTPase activity revealed by the conformation-specific nanobody dynab.

    Science.gov (United States)

    Galli, Valentina; Sebastian, Rafael; Moutel, Sandrine; Ecard, Jason; Perez, Franck; Roux, Aurélien

    2017-10-12

    Dynamin is a large GTPase that forms a helical collar at the neck of endocytic pits, and catalyzes membrane fission (Schmid and Frolov, 2011; Ferguson and De Camilli, 2012). Dynamin fission reaction is strictly dependent on GTP hydrolysis, but how fission is mediated is still debated (Antonny et al., 2016): GTP energy could be spent in membrane constriction required for fission, or in disassembly of the dynamin polymer to trigger fission. To follow dynamin GTP hydrolysis at endocytic pits, we generated a conformation-specific nanobody called dynab, that binds preferentially to the GTP hydrolytic state of dynamin-1. Dynab allowed us to follow the GTPase activity of dynamin-1 in real-time. We show that in fibroblasts, dynamin GTP hydrolysis occurs as stochastic bursts, which are randomly distributed relatively to the peak of dynamin assembly. Thus, dynamin disassembly is not coupled to GTPase activity, supporting that the GTP energy is primarily spent in constriction.

  6. Synthesis of Isomeric Phosphoubiquitin Chains Reveals that Phosphorylation Controls Deubiquitinase Activity and Specificity

    Directory of Open Access Journals (Sweden)

    Nicolas Huguenin-Dezot

    2016-07-01

    Full Text Available Ubiquitin is post-translationally modified by phosphorylation at several sites, but the consequences of these modifications are largely unknown. Here, we synthesize multi-milligram quantities of ubiquitin phosphorylated at serine 20, serine 57, and serine 65 via genetic code expansion. We use these phosphoubiquitins for the enzymatic assembly of 20 isomeric phosphoubiquitin dimers, with different sites of isopeptide linkage and/or phosphorylation. We discover that phosphorylation of serine 20 on ubiquitin converts UBE3C from a dual-specificity E3 ligase into a ligase that primarily synthesizes K48 chains. We profile the activity of 31 deubiquitinases on the isomeric phosphoubiquitin dimers in 837 reactions, and we discover that phosphorylation at distinct sites in ubiquitin can activate or repress cleavage of a particular linkage by deubiquitinases and that phosphorylation at a single site in ubiquitin can control the specificity of deubiquitinases for distinct ubiquitin linkages.

  7. Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity.

    Science.gov (United States)

    Huang, Christine S; Oberbeck, Nina; Hsiao, Yi-Chun; Liu, Peter; Johnson, Adam R; Dixit, Vishva M; Hymowitz, Sarah G

    2018-05-01

    Receptor-interacting protein kinase 4 (RIPK4) is a highly conserved regulator of epidermal differentiation. Members of the RIPK family possess a common kinase domain as well as unique accessory domains that likely dictate subcellular localization and substrate preferences. Mutations in human RIPK4 manifest as Bartsocas-Papas syndrome (BPS), a genetic disorder characterized by severe craniofacial and limb abnormalities. We describe the structure of the murine Ripk4 (MmRipk4) kinase domain, in ATP- and inhibitor-bound forms. The crystallographic dimer of MmRipk4 is similar to those of RIPK2 and BRAF, and we show that the intact dimeric entity is required for MmRipk4 catalytic activity through a series of engineered mutations and cell-based assays. We also assess the impact of BPS mutations on protein structure and activity to elucidate the molecular origins of the disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Rhythmic Components in Extracranial Brain Signals Reveal Multifaceted Task Modulation of Overlapping Neuronal Activity.

    Directory of Open Access Journals (Sweden)

    Roemer van der Meij

    Full Text Available Oscillatory neuronal activity is implicated in many cognitive functions, and its phase coupling between sensors may reflect networks of communicating neuronal populations. Oscillatory activity is often studied using extracranial recordings and compared between experimental conditions. This is challenging, because there is overlap between sensor-level activity generated by different sources, and this can obscure differential experimental modulations of these sources. Additionally, in extracranial data, sensor-level phase coupling not only reflects communicating populations, but can also be generated by a current dipole, whose sensor-level phase coupling does not reflect source-level interactions. We present a novel method, which is capable of separating and characterizing sources on the basis of their phase coupling patterns as a function of space, frequency and time (trials. Importantly, this method depends on a plausible model of a neurobiological rhythm. We present this model and an accompanying analysis pipeline. Next, we demonstrate our approach, using magnetoencephalographic (MEG recordings during a cued tactile detection task as a case study. We show that the extracted components have overlapping spatial maps and frequency content, which are difficult to resolve using conventional pairwise measures. Because our decomposition also provides trial loadings, components can be readily contrasted between experimental conditions. Strikingly, we observed heterogeneity in alpha and beta sources with respect to whether their activity was suppressed or enhanced as a function of attention and performance, and this happened both in task relevant and irrelevant regions. This heterogeneity contrasts with the common view that alpha and beta amplitude over sensory areas are always negatively related to attention and performance.

  9. Integrated Experimental and Model-based Analysis Reveals the Spatial Aspects of EGFR Activation Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Shankaran, Harish; Zhang, Yi; Chrisler, William B.; Ewald, Jonathan A.; Wiley, H. S.; Resat, Haluk

    2012-10-02

    The epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinases, and controls a diverse set of cellular responses relevant to development and tumorigenesis. ErbB activation is a complex process involving receptor-ligand binding, receptor dimerization, phosphorylation, and trafficking (internalization, recycling and degradation), which together dictate the spatio-temporal distribution of active receptors within the cell. The ability to predict this distribution, and elucidation of the factors regulating it, would help to establish a mechanistic link between ErbB expression levels and the cellular response. Towards this end, we constructed mathematical models for deconvolving the contributions of receptor dimerization and phosphorylation to EGFR activation, and to examine the dependence of these processes on sub-cellular location. We collected experimental datasets for EGFR activation dynamics in human mammary epithelial cells, with the specific goal of model parameterization, and used the data to estimate parameters for several alternate models. Model-based analysis indicated that: 1) signal termination via receptor dephosphorylation in late endosomes, prior to degradation, is an important component of the response, 2) less than 40% of the receptors in the cell are phosphorylated at any given time, even at saturating ligand doses, and 3) receptor dephosphorylation rates at the cell surface and early endosomes are comparable. We validated the last finding by measuring EGFR dephosphorylation rates at various times following ligand addition both in whole cells, and in endosomes using ELISAs and fluorescent imaging. Overall, our results provide important information on how EGFR phosphorylation levels are regulated within cells. Further, the mathematical model described here can be extended to determine receptor dimer abundances in cells co-expressing various levels of ErbB receptors. This study demonstrates that an iterative cycle of

  10. Aromatic C-H bond activation revealed by infrared multiphoton dissociation spectroscopy

    Czech Academy of Sciences Publication Activity Database

    Jašíková, L.; Hanikýřová, E.; Schröder, Detlef; Roithová, J.

    2012-01-01

    Roč. 47, č. 4 (2012), s. 460-465 ISSN 1076-5174 Grant - others:GA ČR(CZ) GAP207/11/0338; Seventh Framework Program(XE) 226716 Institutional research plan: CEZ:AV0Z40550506 Keywords : C-H activation * density functional theory calculations * ion spectroscopy * metal oxides * rearrangements Subject RIV: CC - Organic Chemistry Impact factor: 3.214, year: 2012

  11. High-resolution mapping reveals links of HP1 with active and inactive chromatin components.

    Directory of Open Access Journals (Sweden)

    Elzo de Wit

    2007-03-01

    Full Text Available Heterochromatin protein 1 (HP1 is commonly seen as a key factor of repressive heterochromatin, even though a few genes are known to require HP1-chromatin for their expression. To obtain insight into the targeting of HP1 and its interplay with other chromatin components, we have mapped HP1-binding sites on Chromosomes 2 and 4 in Drosophila Kc cells using high-density oligonucleotide arrays and the DNA adenine methyltransferase identification (DamID technique. The resulting high-resolution maps show that HP1 forms large domains in pericentric regions, but is targeted to single genes on chromosome arms. Intriguingly, HP1 shows a striking preference for exon-dense genes on chromosome arms. Furthermore, HP1 binds along entire transcription units, except for 5' regions. Comparison with expression data shows that most of these genes are actively transcribed. HP1 target genes are also marked by the histone variant H3.3 and dimethylated histone 3 lysine 4 (H3K4me2, which are both typical of active chromatin. Interestingly, H3.3 deposition, which is usually observed along entire transcription units, is limited to the 5' ends of HP1-bound genes. Thus, H3.3 and HP1 are mutually exclusive marks on active chromatin. Additionally, we observed that HP1-chromatin and Polycomb-chromatin are nonoverlapping, but often closely juxtaposed, suggesting an interplay between both types of chromatin. These results demonstrate that HP1-chromatin is transcriptionally active and has extensive links with several other chromatin components.

  12. Spores of many common airborne fungi reveal no ice nucleation activity in oil immersion freezing experiments

    Science.gov (United States)

    Pummer, B. G.; Atanasova, L.; Bauer, H.; Bernardi, J.; Druzhinina, I. S.; Fröhlich-Nowoisky, J.; Grothe, H.

    2013-12-01

    Fungal spores are ubiquitous biological aerosols, which are considered to act as ice nuclei. In this study the ice nucleation (IN) activity of spores harvested from 29 fungal strains belonging to 21 different species was tested in the immersion freezing mode by microscopic observation of water-in-oil emulsions. Spores of 8 of these strains were also investigated in a microdroplet freezing array instrument. The focus was laid on species of economical, ecological or sanitary significance. Besides common molds (Ascomycota), some representatives of the widespread group of mushrooms (Basidiomycota) were also investigated. Fusarium avenaceum was the only sample showing IN activity at relatively high temperatures (about 264 K), while the other investigated fungal spores showed no freezing above 248 K. Many of the samples indeed froze at homogeneous ice nucleation temperatures (about 237 K). In combination with other studies, this suggests that only a limited number of species may act as atmospheric ice nuclei. This would be analogous to what is already known for the bacterial ice nuclei. Apart from that, we selected a set of fungal strains from different sites and exposed them to occasional freezing stress during their cultivation. This was in order to test if the exposure to a cold environment encourages the expression of ice nuclei during growth as a way of adaptation. Although the total protein expression was altered by this treatment, it had no significant impact on the IN activity.

  13. Active methanotrophs in two contrasting North American peatland ecosystems revealed using DNA-SIP.

    Science.gov (United States)

    Gupta, Varun; Smemo, Kurt A; Yavitt, Joseph B; Basiliko, Nathan

    2012-02-01

    The active methanotroph community was investigated in two contrasting North American peatlands, a nutrient-rich sedge fen and nutrient-poor Sphagnum bog using in vitro incubations and (13)C-DNA stable-isotope probing (SIP) to measure methane (CH(4)) oxidation rates and label active microbes followed by fingerprinting and sequencing of bacterial and archaeal 16S rDNA and methane monooxygenase (pmoA and mmoX) genes. Rates of CH(4) oxidation were slightly, but significantly, faster in the bog and methanotrophs belonged to the class Alphaproteobacteria and were similar to other methanotrophs of the genera Methylocystis, Methylosinus, and Methylocapsa or Methylocella detected in, or isolated from, European bogs. The fen had a greater phylogenetic diversity of organisms that had assimilated (13)C, including methanotrophs from both the Alpha- and Gammaproteobacteria classes and other potentially non-methanotrophic organisms that were similar to bacteria detected in a UK and Finnish fen. Based on similarities between bacteria in our sites and those in Europe, including Russia, we conclude that site physicochemical characteristics rather than biogeography controlled the phylogenetic diversity of active methanotrophs and that differences in phylogenetic diversity between the bog and fen did not relate to measured CH(4) oxidation rates. A single crenarchaeon in the bog site appeared to be assimilating (13)C in 16S rDNA; however, its phylogenetic similarity to other CO(2)-utilizing archaea probably indicates that this organism is not directly involved in CH(4) oxidation in peat.

  14. Large heterogeneities in comet 67P as revealed by active pits from sinkhole collapse.

    Science.gov (United States)

    Vincent, Jean-Baptiste; Bodewits, Dennis; Besse, Sébastien; Sierks, Holger; Barbieri, Cesare; Lamy, Philippe; Rodrigo, Rafael; Koschny, Detlef; Rickman, Hans; Keller, Horst Uwe; Agarwal, Jessica; A'Hearn, Michael F; Auger, Anne-Thérèse; Barucci, M Antonella; Bertaux, Jean-Loup; Bertini, Ivano; Capanna, Claire; Cremonese, Gabriele; Da Deppo, Vania; Davidsson, Björn; Debei, Stefano; De Cecco, Mariolino; El-Maarry, Mohamed Ramy; Ferri, Francesca; Fornasier, Sonia; Fulle, Marco; Gaskell, Robert; Giacomini, Lorenza; Groussin, Olivier; Guilbert-Lepoutre, Aurélie; Gutierrez-Marques, P; Gutiérrez, Pedro J; Güttler, Carsten; Hoekzema, Nick; Höfner, Sebastian; Hviid, Stubbe F; Ip, Wing-Huen; Jorda, Laurent; Knollenberg, Jörg; Kovacs, Gabor; Kramm, Rainer; Kührt, Ekkehard; Küppers, Michael; La Forgia, Fiorangela; Lara, Luisa M; Lazzarin, Monica; Lee, Vicky; Leyrat, Cédric; Lin, Zhong-Yi; Lopez Moreno, Josè J; Lowry, Stephen; Magrin, Sara; Maquet, Lucie; Marchi, Simone; Marzari, Francesco; Massironi, Matteo; Michalik, Harald; Moissl, Richard; Mottola, Stefano; Naletto, Giampiero; Oklay, Nilda; Pajola, Maurizio; Preusker, Frank; Scholten, Frank; Thomas, Nicolas; Toth, Imre; Tubiana, Cecilia

    2015-07-02

    Pits have been observed on many cometary nuclei mapped by spacecraft. It has been argued that cometary pits are a signature of endogenic activity, rather than impact craters such as those on planetary and asteroid surfaces. Impact experiments and models cannot reproduce the shapes of most of the observed cometary pits, and the predicted collision rates imply that few of the pits are related to impacts. Alternative mechanisms like explosive activity have been suggested, but the driving process remains unknown. Here we report that pits on comet 67P/Churyumov-Gerasimenko are active, and probably created by a sinkhole process, possibly accompanied by outbursts. We argue that after formation, pits expand slowly in diameter, owing to sublimation-driven retreat of the walls. Therefore, pits characterize how eroded the surface is: a fresh cometary surface will have a ragged structure with many pits, while an evolved surface will look smoother. The size and spatial distribution of pits imply that large heterogeneities exist in the physical, structural or compositional properties of the first few hundred metres below the current nucleus surface.

  15. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

    Science.gov (United States)

    Zhyvoloup, Alexander; Melamed, Anat; Anderson, Ian; Planas, Delphine; Lee, Chen-Hsuin; Kriston-Vizi, Janos; Ketteler, Robin; Merritt, Andy; Routy, Jean-Pierre; Ancuta, Petronela; Bangham, Charles R M; Fassati, Ariberto

    2017-07-01

    HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

  16. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

    Directory of Open Access Journals (Sweden)

    Alexander Zhyvoloup

    2017-07-01

    Full Text Available HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

  17. Dietary resveratrol administration increases MnSOD expression and activity in mouse brain

    International Nuclear Information System (INIS)

    Robb, Ellen L.; Winkelmolen, Lieke; Visanji, Naomi; Brotchie, Jonathan; Stuart, Jeffrey A.

    2008-01-01

    trans-Resveratrol (3,4',5-trihydroxystilbene; RES) is of interest for its reported protective effects in a variety of pathologies, including neurodegeneration. Many of these protective properties have been attributed to the ability of RES to reduce oxidative stress. In vitro studies have shown an increase in antioxidant enzyme activities following exposure to RES, including upregulation of mitochondrial superoxide dismutase, an enzyme that is capable of reducing both oxidative stress and cell death. We sought to determine if a similar increase in endogenous antioxidant enzymes is observed with RES treatment in vivo. Three separate modes of RES delivery were utilized; in a standard diet, a high fat diet and through a subcutaneous osmotic minipump. RES given in a high fat diet proved to be effective in elevating antioxidant capacity in brain resulting in an increase in both MnSOD protein level (140%) and activity (75%). The increase in MnSOD was not due to a substantial proliferation of mitochondria, as RES treatment induced a 10% increase in mitochondrial abundance (Citrate Synthase activity). The potential neuroprotective properties of MnSOD have been well established, and we demonstrate that a dietary delivery of RES is able to increase the expression and activity of this enzyme in vivo

  18. Meta-analysis reveals an association between signal transducer and activator of transcription-4 polymorphism and hepatocellular carcinoma risk.

    Science.gov (United States)

    Zhang, Li; Xu, Kuihua; Liu, Chuanmiao; Chen, Jiasheng

    2017-03-01

    Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Signal transducer and activator of transcription (STAT) proteins play a multitude of important functions in liver pathophysiology. Recent studies have indicated associations of rs7574865 single nucleotide polymorphism (SNP) in the STAT4 gene with various autoimmune diseases. The association between STAT4 polymorphism and the risk of HCC has been analyzed in several studies, but results remain inconsistent. This study used a meta-analysis approach to comprehensively investigate the correlation between STAT4 polymorphism and HCC risk based on previously published reports. Studies were searched from the databases of PubMed, EMBase, Web of Science, and the Chinese National Knowledge Infrastructure up to 31 December 2015. The meta-analysis was carried out based on the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Eight published studies, consisting of 7503 HCC patients (cases) and 13 831 individuals without HCC (controls), were included in the present study. Meta-analysis of the included studies revealed that STAT4 rs7574865 polymorphism contributed to the risk of HCC under all four genetic models, consisting of the allelic model (G vs. T: odds ratio [OR], 1.25; 95% confidence interval [CI], 1.19-1.30), the dominant effect model (GG + GT vs. TT: OR, 1.52; 95% CI, 1.26-1.84), the recessive effect model (GG vs. GT + TT: OR, 1.35; 95% CI, 1.21-1.50), and the co-dominant effect model (GG vs.. TT: OR, 1.72; 95% CI, 1.42-2.10) comparisons. No publication bias was indicated from either visualization of the funnel plot or Egger's test. A significantly increased risk of HCC associated with the rs7574865 G was found. The rs7574865 polymorphism might be used as one risk factor for HCC. © 2016 The Japan Society of Hepatology.

  19. Activation of the Ca2+-sensing receptors increases currents through inward rectifier K+ channels via activation of phosphatidylinositol 4-kinase.

    Science.gov (United States)

    Liu, Chung-Hung; Chang, Hsueh-Kai; Lee, Sue-Ping; Shieh, Ru-Chi

    2016-11-01

    Inward rectifier K + channels are important for maintaining normal electrical function in many cell types. The proper function of these channels requires the presence of membrane phosphoinositide 4,5-bisphosphate (PIP 2 ). Stimulation of the Ca 2+ -sensing receptor CaR, a pleiotropic G protein-coupled receptor, activates both G q/11 , which decreases PIP 2 , and phosphatidylinositol 4-kinase (PI-4-K), which, conversely, increases PIP 2 . How membrane PIP 2 levels are regulated by CaR activation and whether these changes modulate inward rectifier K + are unknown. In this study, we found that activation of CaR by the allosteric agonist, NPSR568, increased inward rectifier K + current (I K1 ) in guinea pig ventricular myocytes and currents mediated by Kir2.1 channels exogenously expressed in HEK293T cells with a similar sensitivity. Moreover, using the fluorescent PIP 2 reporter tubby-R332H-cYFP to monitor PIP 2 levels, we found that CaR activation in HEK293T cells increased membrane PIP 2 concentrations. Pharmacological studies showed that both phospholipase C (PLC) and PI-4-K are activated by CaR stimulation with the latter played a dominant role in regulating membrane PIP 2 and, thus, Kir currents. These results provide the first direct evidence that CaR activation upregulates currents through inward rectifier K + channels by accelerating PIP 2 synthesis. The regulation of I K1 plays a critical role in the stability of the electrical properties of many excitable cells, including cardiac myocytes and neurons. Further, synthetic allosteric modulators that increase CaR activity have been used to treat hyperparathyroidism, and negative CaR modulators are of potential importance in the treatment of osteoporosis. Thus, our results provide further insight into the roles played by CaR in the cardiovascular system and are potentially valuable for heart disease treatment and drug safety.

  20. Increased angiotensin-converting enzyme activity in the left ventricle after infarction

    Directory of Open Access Journals (Sweden)

    V.C.W. Busatto

    1997-05-01

    Full Text Available An increase in angiotensin-converting enzyme (ACE activity has been observed in the heart after myocardial infarction (MI. Since most studies have been conducted in chronically infarcted individuals exhibiting variable degrees of heart failure, the present study was designed to determine ACE activity in an earlier phase of MI, before heart failure development. MI was produced in 3-month old male Wistar rats by ligation of the anterior branches of the left coronary artery, control rats underwent sham surgery and the animals were studied 7 or 15 days later. Hemodynamic data obtained for the anesthetized animals showed normal values of arterial blood pressure and of end-diastolic pressure in the right and left ventricular cavities of MI rats. Right and left ventricular (RV, LV muscle and scar tissue homogenates were prepared to determine ACE activity in vitro by measuring the velocity of His-Leu release from the synthetic substrate Hyp-His-Leu. ACE activity was corrected to the tissue wet weight and is reported as nmol His-Leu g-1 min-1. No significant change in ACE activity in the RV homogenates was demonstrable. A small nonsignificant increase of ACE activity (11 ± 9%; P0.05 was observed 7 days after MI in the surviving left ventricular muscle. Two weeks after surgery, however, ACE activity was 46 ± 11% (P<0.05 higher in infarcted rats compared to sham-operated rats. The highest ACE activity was demonstrable in the scar tissue homogenate. In rats studied two weeks after surgery, ACE activity in the LV muscle increased from 105 ± 7 nmol His-Leu g-1 min-1 in control hearts to 153 ± 11 nmol His-Leu g-1 min-1 (P<0.05 in the remaining LV muscle of MI rats and to 1051 ± 208 nmol His-Leu g-1 min-1 (P<0.001 in the fibrous scar. These data indicate that ACE activity increased in the heart after infarction before heart failure was demonstrable by hemodynamic measurements. Since the blood vessels of the scar drain to the remaining LV myocardium, the

  1. Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus.

    Science.gov (United States)

    Chen, Qian; Xiao, De-Sheng

    2014-01-30

    Adult hippocampus is highly vulnerable to iron-induced oxidative stress. Aerobic exercise has been proposed to reduce oxidative stress but the findings in the hippocampus are conflicting. This study aimed to observe the changes of redox-active iron and concomitant regulation of cellular iron homeostasis in the hippocampus by aerobic exercise, and possible regulatory effect of nitric oxide (NO). A randomized controlled study was designed in the rats with swimming exercise treatment (for 3 months) and/or an unselective inhibitor of NO synthase (NOS) (L-NAME) treatment. The results from the bleomycin-detectable iron assay showed additional redox-active iron in the hippocampus by exercise treatment. The results from nonheme iron content assay, combined with the redox-active iron content, showed increased storage iron content by exercise treatment. NOx (nitrate plus nitrite) assay showed increased NOx content by exercise treatment. The results from the Western blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS. In these effects of exercise treatment, the increased redox-active iron content, storage iron content, IRP1 and IRP2 expressions were completely reversed by L-NAME treatment, and decreased ferroportin expression was in part reversed by L-NAME. L-NAME treatment completely inhibited increased NOx and both eNOS and nNOS expression in the hippocampus. Our findings suggest that aerobic exercise could increase the redox-active iron in the hippocampus, indicating an increase in the capacity to generate hydroxyl radicals through the Fenton reactions, and aerobic exercise-induced iron accumulation in the hippocampus might mainly result from the role of the endogenous NO. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Increased cell surface metallopeptidase activity in cells undergoing UV-induced apoptosis

    International Nuclear Information System (INIS)

    Piva, T.J.; Davern, C.M.; Ellem, K.A.O.

    1999-01-01

    Full text: We have previously shown that UVC irradiation activated a range of cell surface peptidases (CSP) in HeLa cell monolayer cultures 20 h post-irradiation (1). In cells undergoing apoptosis there is an increase in CSP activity compared to control viable cells in cultures which have been treated by a wide range of agents including UV-irradiation (2). In order to further understand the mechanism involved in this process, we induced apoptosis in HeLa cells using 500 Jm -2 UVB. The separation of viable, apoptotic and necrotic cells of irradiated HeLa cell cultures was made by FACS analysis and sorting. The three populations were distinguished by their staining with PI and Hoechst 33342 dyes. CSP activity was measured using the P9 assay developed in this laboratory (1-3). The viable fraction of the irradiated cells had a higher level of CSP activity compared to unirradiated controls. The level of CSP activity in the apoptotic fraction was higher than that of the viable fraction, however that of the necrotic fraction was significantly lower. This finding agreed with that seen in UVC-irradiated (50 Jm -2 ) cultures (2). In order to elucidate the mechanism by which CSP activity was increased in UVB-irradiated cells undergoing apoptosis, the cultures were treated with the following agents: bestatin, aminopeptidase inhibitor, DEVD, caspase 3 inhibitor, and 3-aminobenzamide (3AB), PARP activation inhibitor. Bestatin and DEVD did not affect the level of CSP activity in the different cell subpopulations following UVB-irradiation. Treatment with 3AB abolished the increased CSP activity seen in the viable and apoptotic fraction following UVB-irradiation. All treated cells had the same morphology as observed under EM. The degree of phosphatidylserine eversion on the cell membrane was similar as were the cleavage profiles of PARP and actin. Only DEVD-treated cells had reduced caspase 3 activity which confirmed that the activation of CSP activity in apoptotic cells is

  3. Integrative exercise and lifestyle intervention increases leisure-time activity in breast cancer patients

    DEFF Research Database (Denmark)

    Casla, Soraya; Hojman, Pernille; Cubedo, Ricardo

    2014-01-01

    BACKGROUND: Physical activity has been demonstrated to increase survival in breast cancer patients, but few breast cancer patients meet the general recommendations for physical activity. The aim of this pilot study was to investigate if a supervised integrated counseling and group-based exercise...... program could increase leisure-time activity in women with breast cancer. METHODS: This pilot project, designed as a single-arm study with pre-post testing, consisted of 24 classes of combined aerobic and strength exercise training as well as classes on dietary and health behavior. A total of 48 women...... with breast cancer who were undergoing or had recently completed anticancer treatment completed the study. Leisure-time physical activity, grip strength, functional capacity, quality of life (QoL), and depression were assessed at baseline, after intervention, and at the 12-week follow-up after intervention...

  4. Acute Exercise Increases Plasma Total Antioxidant Status and Antioxidant Enzyme Activities in Untrained Men

    Directory of Open Access Journals (Sweden)

    C. Berzosa

    2011-01-01

    Full Text Available Antioxidant defences are essential for cellular redox regulation. Since free-radical production may be enhanced by physical activity, herein, we evaluated the effect of acute exercise on total antioxidant status (TAS and the plasma activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase and its possible relation to oxidative stress resulting from exercise. Healthy untrained male subjects (=34 performed three cycloergometric tests, including maximal and submaximal episodes. Venous blood samples were collected before and immediately after each different exercise. TAS and enzyme activities were assessed by spectrophotometry. An increase of the antioxidant enzyme activities in plasma was detected after both maximal and submaximal exercise periods. Moreover, under our experimental conditions, exercise also led to an augmentation of TAS levels. These findings are consistent with the idea that acute exercise may play a beneficial role because of its ability to increase antioxidant defense mechanisms through a redox sensitive pathway.

  5. Composted Cattle Manure Increases Microbial Activity and Soil Fertility More Than Composted Swine Manure in a Submerged Rice Paddy

    Directory of Open Access Journals (Sweden)

    Suvendu Das

    2017-09-01

    Full Text Available Livestock waste composts with minimum inorganic fertilizer as a soil amendment in low-input intensive farming are a feasible agricultural practice to improve soil fertility and productivity and to mitigate soil degradation. The key benefits of the practice rely on the activities of soil microorganisms. However, the role of different livestock composts [composted cattle manure (CCM vs. composted swine manure (CSM] on soil microbes, their activities and the overall impact on soil fertility and productivity in a flooded paddy remains elusive. This study compares the effectiveness of CCM and CSM amendment on bacterial communities, activities, nutrient availability, and crop yield in a flooded rice cropping system. We used deep 16S amplicon sequencing and soil enzyme activities to decipher bacterial communities and activities, respectively. Both CCM and CSM amendment significantly increased soil pH, nutrient availability (C, N, and P, microbial biomass, soil enzyme activities indicative for C and N cycles, aboveground plant biomass and grain yield. And the increase in above-mentioned parameters was more prominent in the CCM treatment compared to the CSM treatment. The CCM amendment increased species richness and stimulated copiotrophic microbial groups (Alphaproteobacteria, Betaproteobacteria, and Firmicutes which are often involved in degradation of complex organic compounds. Moreover, some dominant species (e.g., Azospirillum zeae, Azospirillum halopraeferens, Azospirillum rugosum, Clostridium alkalicellulosi, Clostridium caenicola, Clostridium termitidis, Clostridium cellulolyticum, Magnetospirillum magnetotacticum, Pleomorphomonas oryzae, Variovorax boronicumulans, Pseudomonas xanthomarina, Pseudomonas stutzeri, and Bacillus niacini which have key roles in plant growth promotion and/or lignocellulose degradation were enhanced under CCM treatment compared to CSM treatment. Multivariate analysis revealed that soil pH and available carbon (C and

  6. AMPK activation through mitochondrial regulation results in increased substrate oxidation and improved metabolic parameters in models of diabetes.

    Directory of Open Access Journals (Sweden)

    Yonchu Jenkins

    Full Text Available Modulation of mitochondrial function through inhibiting respiratory complex I activates a key sensor of cellular energy status, the 5'-AMP-activated protein kinase (AMPK. Activation of AMPK results in the mobilization of nutrient uptake and catabolism for mitochondrial ATP generation to restore energy homeostasis. How these nutrient pathways are affected in the presence of a potent modulator of mitochondrial function and the role of AMPK activation in these effects remain unclear. We have identified a molecule, named R419, that activates AMPK in vitro via complex I inhibition at much lower concentrations than metformin (IC50 100 nM vs 27 mM, respectively. R419 potently increased myocyte glucose uptake that was dependent on AMPK activation, while its ability to suppress hepatic glucose production in vitro was not. In addition, R419 treatment of mouse primary hepatocytes increased fatty acid oxidation and inhibited lipogenesis in an AMPK-dependent fashion. We have performed an extensive metabolic characterization of its effects in the db/db mouse diabetes model. In vivo metabolite profiling of R419-treated db/db mice showed a clear upregulation of fatty acid oxidation and catabolism of branched chain amino acids. Additionally, analyses performed using both (13C-palmitate and (13C-glucose tracers revealed that R419 induces complete oxidation of both glucose and palmitate to CO2 in skeletal muscle, liver, and adipose tissue, confirming that the compound increases mitochondrial function in vivo. Taken together, our results show that R419 is a potent inhibitor of complex I and modulates mitochondrial function in vitro and in diabetic animals in vivo. R419 may serve as a valuable molecular tool for investigating the impact of modulating mitochondrial function on nutrient metabolism in multiple tissues and on glucose and lipid homeostasis in diabetic animal models.

  7. INCREASING EFL STUDENTS’ WRITING ABILITIES USING PEER RESPONSE ACTIVITIES VIA FACEBOOK

    Directory of Open Access Journals (Sweden)

    M. Zaini Miftah

    2016-12-01

    Full Text Available This study was aimed to increase EFL students’ abilities in writing argumentative essay via Facebook by developing peer response activities. The classroom action research was employed in cyclic activities. The subjects were 25 Indonesian fourth-year undergraduate EFL students who enrolled in Writing III course. The data were gained from writing task, observation, and field notes. The result shows that this strategy with the appropriate instructional procedures can increase the EFL students’ abilities in writing argumentative essay. It is indicated by the increases of the students’ writing achievement and involvement in writing class during peer response activities via Facebook. Hence, it gives insights to employ this way as an alternative teaching technique in writing classroom because of its effectiveness.

  8. Increasing EFL Students’ Writing Abilities Using Peer Response Activities via Facebook

    Directory of Open Access Journals (Sweden)

    M. Zaini Miftah

    2016-12-01

    Full Text Available This study was aimed to increase EFL students’ abilities in writing argumentative essay via Facebook by developing peer response activities. The classroom action research was employed in cyclic activities. The subjects were 25 Indonesian fourth-year undergraduate EFL students who enrolled in Writing III course. The data were gained from writing task, observation, and field notes. The result shows that this strategy with the appropriate instructional procedures can increase the EFL students’ abilities in writing argumentative essay. It is indicated by the increases of the students’ writing achievement and involvement in writing class during peer response activities via Facebook. Hence, it gives insights to employ this way as an alternative teaching technique in writing classroom because of its effectiveness.

  9. 31P NMR Spectroscopy Revealed Adenylate kinase-like Activity and Phosphotransferase-like Activity from F1-ATPase of Escherichia coli

    International Nuclear Information System (INIS)

    Kim, Hyun Won

    2011-01-01

    Adenylate kinase-like activity and phosphotransferase-like activity from F 1 -ATPase of Escherichia coli was revealed by 31 P NMR spectroscopy. Incubation of F 1 -ATPase with ADP in the presence of Mg 2+ shows the appearance of 31 P resonances from AMP and Pi, suggesting generation of AMP and ATP by adenylate kinase-like activity and the subsequent hydrolysis to Pi. Incubation of F1-ATPase with ADP in the presence of methanol shows additional peak from methyl phosphate, suggesting phosphotransferase-like activity of F 1 -ATPase. Both adenylate kinase-like activity and phosphotransferase-like activity has not been reported from F 1 -ATPase of Escherichia coli. 31 P NMR could be a valuable tool for the investigation of phosphorous related enzyme

  10. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

    Science.gov (United States)

    Banerjee, Soumyabrata; Poddar, Mrinal K

    2015-03-01

    Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  11. Quantitative cell signalling analysis reveals down-regulation of MAPK pathway activation in colorectal cancer.

    LENUS (Irish Health Repository)

    Gulmann, Christian

    2009-08-01

    Mitogen-activated protein kinases (MAPK) are considered to play significant roles in colonic carcinogenesis and kinase inhibitor therapy has been proposed as a potential tool in the treatment of this disease. Reverse-phase microarray assays using phospho-specific antibodies can directly measure levels of phosphorylated protein isoforms. In the current study, samples from 35 cases of untreated colorectal cancer colectomies were laser capture-microdissected to isolate epithelium and stroma from cancer as well as normal (i.e. uninvolved) mucosa. Lysates generated from these four tissue types were spotted onto reverse-phase protein microarrays and probed with a panel of antibodies to ERK, p-ERK, p38, p-p38, p-JNK, MEK and p-MEK. Whereas total protein levels were unchanged, or slightly elevated (p38, p = 0.0025) in cancers, activated isoforms, including p-ERK, p-p38 and p-JNK, were decreased two- to four-fold in cancers compared with uninvolved mucosa (p < 0.0023 in all cases except for p-JNK in epithelium, where decrement was non-significant). This was backed up by western blotting. Dukes\\' stage B and C cancers displayed lower p-ERK and p-p38 expression than Dukes\\' stage A cancers, although this was not statistically significant. It is concluded that MAPK activity may be down-regulated in colorectal cancer and that further exploration of inhibitory therapy in this system should be carefully evaluated if this finding is confirmed in larger series.

  12. Theoretical Insights Reveal Novel Motions in Csk's SH3 Domain That Control Kinase Activation.

    Directory of Open Access Journals (Sweden)

    Sulyman Barkho

    Full Text Available The Src family of tyrosine kinases (SFKs regulate numerous aspects of cell growth and differentiation and are under the principal control of the C-terminal Src Kinase (Csk. Although Csk and SFKs share conserved kinase, SH2 and SH3 domains, they differ considerably in three-dimensional structure, regulatory mechanism, and the intrinsic kinase activities. Although the SH2 and SH3 domains are known to up- or down-regulate tyrosine kinase function, little is known about the global motions in the full-length kinase that govern these catalytic variations. We use a combination of accelerated Molecular Dynamics (aMD simulations and experimental methods to provide a new view of functional motions in the Csk scaffold. These computational studies suggest that high frequency vibrations in the SH2 domain are coupled through the N-terminal lobe of the kinase domain to motions in the SH3 domain. The effects of these reflexive movements on the kinase domain can be viewed using both Deuterium Exchange Mass Spectrometry (DXMS and steady-state kinetic methods. Removal of several contacts, including a crystallographically unobserved N-terminal segment, between the SH3 and kinase domains short-circuit these coupled motions leading to reduced catalytic efficiency and stability of N-lobe motifs within the kinase domain. The data expands the model of Csk's activation whereby separate domains productively interact with two diametrically opposed surfaces of the kinase domain. Such reversible transitions may organize the active structure of the tyrosine kinase domain of Csk.

  13. Revealing the Origin of Activity in Nitrogen-Doped Nanocarbons towards Electrocatalytic Reduction of Carbon Dioxide

    DEFF Research Database (Denmark)

    Xu, Junyuan; Kan, Yuhe; Huang, Rui

    2016-01-01

    Carbon nanotubes (CNTs) are functionalized with nitrogen atoms for reduction of carbon dioxide (CO2). The investigation explores the origin of the catalyst’s activity and the role of nitrogen chemical states therein. The catalysts show excellent performances, with about 90% current efficiency...... for CO formation and stability over 60 hours. The Tafel analyses and density functional theory calculations suggest that the reduction of CO2 proceeds through an initial rate-determining transfer of one electron to CO2, which leads to the formation of carbon dioxide radical anion (CO2C). The initial...

  14. Construction of Mutant Glucose Oxidases with Increased Dye-Mediated Dehydrogenase Activity

    Science.gov (United States)

    Horaguchi, Yohei; Saito, Shoko; Kojima, Katsuhiro; Tsugawa, Wakako; Ferri, Stefano; Sode, Koji

    2012-01-01

    Mutagenesis studies on glucose oxidases (GOxs) were conducted to construct GOxs with reduced oxidase activity and increased dehydrogenase activity. We focused on two representative GOxs, of which crystal structures have already been reported—Penicillium amagasakiense GOx (PDB ID; 1gpe) and Aspergillus niger GOx (PDB ID; 1cf3). We constructed oxygen-interacting structural models for GOxs, and predicted the residues responsible for oxidative half reaction with oxygen on the basis of the crystal structure of cholesterol oxidase as well as on the fact that both enzymes are members of the glucose/methanol/choline (GMC) oxidoreductase family. Rational amino acid substitution resulted in the construction of an engineered GOx with drastically decreased oxidase activity and increased dehydrogenase activity, which was higher than that of the wild-type enzyme. As a result, the dehydrogenase/oxidase ratio of the engineered enzyme was more than 11-fold greater than that of the wild-type enzyme. These results indicate that alteration of the dehydrogenase/oxidase activity ratio of GOxs is possible by introducing a mutation into the putative functional residues responsible for oxidative half reaction with oxygen of these enzymes, resulting in a further increased dehydrogenase activity. This is the first study reporting the alteration of GOx electron acceptor preference from oxygen to an artificial electron acceptor. PMID:23203056

  15. Construction of Mutant Glucose Oxidases with Increased Dye-Mediated Dehydrogenase Activity

    Directory of Open Access Journals (Sweden)

    Koji Sode

    2012-11-01

    Full Text Available Mutagenesis studies on glucose oxidases (GOxs were conducted to construct GOxs with reduced oxidase activity and increased dehydrogenase activity. We focused on two representative GOxs, of which crystal structures have already been reported—Penicillium amagasakiense GOx (PDB ID; 1gpe and Aspergillus niger GOx (PDB ID; 1cf3. We constructed oxygen-interacting structural models for GOxs, and predicted the residues responsible for oxidative half reaction with oxygen on the basis of the crystal structure of cholesterol oxidase as well as on the fact that both enzymes are members of the glucose/methanol/choline (GMC oxidoreductase family. Rational amino acid substitution resulted in the construction of an engineered GOx with drastically decreased oxidase activity and increased dehydrogenase activity, which was higher than that of the wild-type enzyme. As a result, the dehydrogenase/oxidase ratio of the engineered enzyme was more than 11-fold greater than that of the wild-type enzyme. These results indicate that alteration of the dehydrogenase/oxidase activity ratio of GOxs is possible by introducing a mutation into the putative functional residues responsible for oxidative half reaction with oxygen of these enzymes, resulting in a further increased dehydrogenase activity. This is the first study reporting the alteration of GOx electron acceptor preference from oxygen to an artificial electron acceptor.

  16. Construction of mutant glucose oxidases with increased dye-mediated dehydrogenase activity.

    Science.gov (United States)

    Horaguchi, Yohei; Saito, Shoko; Kojima, Katsuhiro; Tsugawa, Wakako; Ferri, Stefano; Sode, Koji

    2012-11-02

    Mutagenesis studies on glucose oxidases (GOxs) were conducted to construct GOxs with reduced oxidase activity and increased dehydrogenase activity. We focused on two representative GOxs, of which crystal structures have already been reported—Penicillium amagasakiense GOx (PDB ID; 1gpe) and Aspergillus niger GOx (PDB ID; 1cf3). We constructed oxygen-interacting structural models for GOxs, and predicted the residues responsible for oxidative half reaction with oxygen on the basis of the crystal structure of cholesterol oxidase as well as on the fact that both enzymes are members of the glucose/methanol/choline (GMC) oxidoreductase family. Rational amino acid substitution resulted in the construction of an engineered GOx with drastically decreased oxidase activity and increased dehydrogenase activity, which was higher than that of the wild-type enzyme. As a result, the dehydrogenase/oxidase ratio of the engineered enzyme was more than 11-fold greater than that of the wild-type enzyme. These results indicate that alteration of the dehydrogenase/oxidase activity ratio of GOxs is possible by introducing a mutation into the putative functional residues responsible for oxidative half reaction with oxygen of these enzymes, resulting in a further increased dehydrogenase activity. This is the first study reporting the alteration of GOx electron acceptor preference from oxygen to an artificial electron acceptor.

  17. Physiological activation of the human cerebral cortex during auditory perception and speech revealed by regional increases in cerebral blood flow

    DEFF Research Database (Denmark)

    Lassen, N A; Friberg, L

    1988-01-01

    by measuring regional cerebral blood flow CBF after intracarotid Xenon-133 injection are reviewed with emphasis on tests involving auditory perception and speech, and approach allowing to visualize Wernicke and Broca's areas and their contralateral homologues in vivo. The completely atraumatic tomographic CBF...

  18. Optogenetic activation of CA1 pyramidal neurons at the dorsal and ventral hippocampus evokes distinct brain-wide responses revealed by mouse fMRI.

    Directory of Open Access Journals (Sweden)

    Norio Takata

    Full Text Available The dorsal and ventral hippocampal regions (dHP and vHP are proposed to have distinct functions. Electrophysiological studies have revealed intra-hippocampal variances along the dorsoventral axis. Nevertheless, the extra-hippocampal influences of dHP and vHP activities remain unclear. In this study, we compared the spatial distribution of brain-wide responses upon dHP or vHP activation and further estimate connection strengths between the dHP and the vHP with corresponding extra-hippocampal areas. To achieve this, we first investigated responses of local field potential (LFP and multi unit activities (MUA upon light stimulation in the hippocampus of an anesthetized transgenic mouse, whose CA1 pyramidal neurons expressed a step-function opsin variant of channelrhodopsin-2 (ChR2. Optogenetic stimulation increased hippocampal LFP power at theta, gamma, and ultra-fast frequency bands, and augmented MUA, indicating light-induced activation of CA1 pyramidal neurons. Brain-wide responses examined using fMRI revealed that optogenetic activation at the dHP or vHP caused blood oxygenation level-dependent (BOLD fMRI signals in situ. Although activation at the dHP induced BOLD responses at the vHP, the opposite was not observed. Outside the hippocampal formation, activation at the dHP, but not the vHP, evoked BOLD responses at the retrosplenial cortex (RSP, which is in line with anatomical evidence. In contrast, BOLD responses at the lateral septum (LS were induced only upon vHP activation, even though both dHP and vHP send axonal fibers to the LS. Our findings suggest that the primary targets of dHP and vHP activation are distinct, which concurs with attributed functions of the dHP and RSP in spatial memory, as well as of the vHP and LS in emotional responses.

  19. Colocalization of Galectin-3 With CD147 Is Associated With Increased Gelatinolytic Activity in Ulcerating Human Corneas.

    Science.gov (United States)

    Cruzat, Andrea; Gonzalez-Andrades, Miguel; Mauris, Jérôme; AbuSamra, Dina B; Chidambaram, Preethi; Kenyon, Kenneth R; Chodosh, James; Dohlman, Claes H; Argüeso, Pablo

    2018-01-01

    Galectin-3 is a carbohydrate-binding protein known to promote expression of matrix metalloproteinases, a hallmark of ulceration, through interaction with the extracellular matrix metalloproteinase inducer CD147. The aim of this study was to investigate the distribution of galectin-3 in corneas of patients with ulcerative keratitis and to determine its relationship to CD147 and the presence of gelatinolytic activity. This was an observational case series involving donor tissue from 13 patients with active corneal ulceration and 6 control corneas. Fixed-frozen sections of the corneas were processed to localize galectin-3 and CD147 by immunofluorescence microscopy. Gelatinolytic activity was detected by in situ zymography. Tissue from patients with active corneal ulceration showed a greater galectin-3 immunoreactivity in basal epithelia and stroma compared with controls. Immunofluorescence grading scores revealed increased colocalization of galectin-3 and CD147 in corneal ulcers at the epithelial-stromal junction and within fibroblasts. Quantitative analysis using the Manders' colocalization coefficient demonstrated significant overlap in corneas from patients with ulcerative keratitis (M1 = 0.29; M2 = 0.22) as opposed to control corneas (M1 = 0.01, P < 0.01; M2 = 0.02, P < 0.05). In these experiments, there was a significant positive correlation between the degree of galectin-3 and CD147 colocalization and the presence of gelatinolytic activity. Our results indicate that concomitant stimulation and colocalization of galectin-3 with CD147 are associated with increased gelatinolytic activity in the actively ulcerating human cornea and suggest a mechanism by which galectin-3 may contribute to the degradation of extracellular matrix proteins during ulceration.

  20. Activity of pyramidal I and II slip in Mg alloys as revealed by texture development

    Science.gov (United States)

    Zecevic, Miroslav; Beyerlein, Irene J.; Knezevic, Marko

    2018-02-01

    Due to the geometry of the hexagonal close-packed (HCP) lattice, there are two types of pyramidal slip modes: { 10 1 bar 1 } 〈 11 2 bar 3 bar 〉 or type I and { 1 bar 1 bar 22 } 〈 11 2 bar 3 〉 or type II in HCP crystalline materials. Here we use crystal plasticity to examine the importance of crystallographic slip by pyramidal type I and type II on texture evolution. The study is applied to an Mg-4%Li alloy. An elastic-plastic polycrystal model is employed to elucidate the reorientation tendencies of these two slip modes in rolling of a textured polycrystal. Comparisons with experimental texture measurements indicate that both pyramidal I and II type slip were active during rolling deformation, with pyramidal I being the dominant mode. A single-slip-mode analysis is used to identify the orientations that prefer pyramidal I vs. II type slip when acting alone in a crystal. The analysis applies not only to Mg-4%Li, but identifies the key texture components in HCP crystals that would help distinguish the activity of pyramidal I from pyramidal II slip in rolling deformation.

  1. High resolution in situ zymography reveals matrix metalloproteinase activity at glutamatergic synapses.

    Science.gov (United States)

    Gawlak, M; Górkiewicz, T; Gorlewicz, A; Konopacki, F A; Kaczmarek, L; Wilczynski, G M

    2009-01-12

    Synaptic plasticity involves remodeling of extracellular matrix. This is mediated, in part, by enzymes of the matrix metalloproteinase (MMP) family, in particular by gelatinase MMP-9. Accordingly, there is a need of developing methods to visualize gelatinolytic activity at the level of individual synapses, especially in the context of neurotransmitters receptors. Here we present a high-resolution fluorescent in situ zymography (ISZ), performed in thin sections of the alcohol-fixed and polyester wax-embedded brain tissue of the rat (Rattus norvegicus), which is superior to the current ISZ protocols. The method allows visualization of structural details up to the resolution-limit of light microscopy, in conjunction with immunofluorescent labeling. We used this technique to visualize and quantify gelatinolytic activity at the synapses in control and seizure-affected rat brain. In particular, we demonstrated, for the first time, frequent colocalization of gelatinase(s) with synaptic N-methyl-D-aspartic acid (NMDA)- and AMPA-type glutamate receptors. We believe that our method represents a valuable tool to study extracellular proteolytic processes at the synapses, it could be used, as well, to investigate proteinase involvement in a range of physiological and pathological phenomena in the nervous system.

  2. Deep sequencing of subseafloor eukaryotic rRNA reveals active Fungi across marine subsurface provinces.

    Directory of Open Access Journals (Sweden)

    William Orsi

    Full Text Available The deep marine subsurface is a vast habitat for microbial life where cells may live on geologic timescales. Because DNA in sediments may be preserved on long timescales, ribosomal RNA (rRNA is suggested to be a proxy for the active fraction of a microbial community in the subsurface. During an investigation of eukaryotic 18S rRNA by amplicon pyrosequencing, unique profiles of Fungi were found across a range of marine subsurface provinces including ridge flanks, continental margins, and abyssal plains. Subseafloor fungal populations exhibit statistically significant correlations with total organic carbon (TOC, nitrate, sulfide, and dissolved inorganic carbon (DIC. These correlations are supported by terminal restriction length polymorphism (TRFLP analyses of fungal rRNA. Geochemical correlations with fungal pyrosequencing and TRFLP data from this geographically broad sample set suggests environmental selection of active Fungi in the marine subsurface. Within the same dataset, ancient rRNA signatures were recovered from plants and diatoms in marine sediments ranging from 0.03 to 2.7 million years old, suggesting that rRNA from some eukaryotic taxa may be much more stable than previously considered in the marine subsurface.

  3. Active Tension Network model reveals an exotic mechanical state realized in epithelial tissues

    Science.gov (United States)

    Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streicha, Sebastian; Shraiman, Boris

    Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that mechanical balance of cells is dominated by cortical tension and introduces tension dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties: i) ATN behaves as a fluid at short times, but at long times it supports external tension, like a solid; ii) its mechanical equilibrium state has extensive degeneracy associated with a discrete conformal - ''isogonal'' - deformation of cells. ATN model predicts a constraint on equilibrium cell geometry, which we demonstrate to hold in certain epithelial tissues. We further show that isogonal modes are observed in a fruit fly embryo, accounting for the striking variability of apical area of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, understanding which helps understand biological phenomena.

  4. Revealing the Origin of Activity in Nitrogen-Doped Nanocarbons towards Electrocatalytic Reduction of Carbon Dioxide.

    Science.gov (United States)

    Xu, Junyuan; Kan, Yuhe; Huang, Rui; Zhang, Bingsen; Wang, Bolun; Wu, Kuang-Hsu; Lin, Yangming; Sun, Xiaoyan; Li, Qingfeng; Centi, Gabriele; Su, Dangsheng

    2016-05-23

    Carbon nanotubes (CNTs) are functionalized with nitrogen atoms for reduction of carbon dioxide (CO2 ). The investigation explores the origin of the catalyst's activity and the role of nitrogen chemical states therein. The catalysts show excellent performances, with about 90 % current efficiency for CO formation and stability over 60 hours. The Tafel analyses and density functional theory calculations suggest that the reduction of CO2 proceeds through an initial rate-determining transfer of one electron to CO2 , which leads to the formation of carbon dioxide radical anion (CO2 (.-) ). The initial reduction barrier is too high on pristine CNTs, resulting in a very high overpotentials at which the hydrogen evolution reaction dominates over CO2 reduction. The doped nitrogen atoms stabilize the radical anion, thereby lowering the initial reduction barrier and improving the intrinsic activity. The most efficient nitrogen chemical state for this reaction is quaternary nitrogen, followed by pyridinic and pyrrolic nitrogen. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Active sites of two orthologous cytochromes P450 2E1: Differences revealed by spectroscopic methods

    International Nuclear Information System (INIS)

    Anzenbacherova, Eva; Hudecek, Jiri; Murgida, Daniel; Hildebrandt, Peter; Marchal, Stephane; Lange, Reinhard; Anzenbacher, Pavel

    2005-01-01

    Cytochromes P450 2E1 of human and minipig origin were examined by absorption spectroscopy under high hydrostatic pressure and by resonance Raman spectroscopy. Human enzyme tends to denature to the P420 form more easily than the minipig form; moreover, the apparent compressibility of the heme active site (as judged from a redshift of the absorption maximum with pressure) is greater than that of the minipig counterpart. Relative compactness of the minipig enzyme is also seen in the Raman spectra, where the presence of planar heme conformation was inferred from band positions characteristic of the low-spin heme with high degree of symmetry. In this respect, the CYP2E1 seems to be another example of P450 conformational heterogeneity as shown, e.g., by Davydov et al. for CYP3A4 [Biochem. Biophys. Res. Commun. 312 (2003) 121-130]. The results indicate that the flexibility of the CYP active site is likely one of its basic structural characteristics

  6. Troxerutin Reduces Kidney Damage against BDE-47-Induced Apoptosis via Inhibiting NOX2 Activity and Increasing Nrf2 Activity

    Directory of Open Access Journals (Sweden)

    Qun Shan

    2017-01-01

    Full Text Available 2,2,4,4-Tetrabromodiphenyl ether (BDE-47, one of the persistent organic pollutants, seriously influences the quality of life; however, its pathological mechanism remains unclear. Troxerutin is a flavonoid with pharmacological activity of antioxidation and anti-inflammation. In the present study, we investigated troxerutin against BDE-47-induced kidney cell apoptosis and explored the underlying mechanism. The results show that troxerutin reduced renal cell apoptosis and urinary protein secretion in BDE-47-treated mice. Western blot analysis shows that troxerutin supplement enhanced the ratio of Bcl-2/Bax; inhibited the release of cytochrome c from mitochondria, the activation of procaspase-9 and procaspase-3, and the cleavage of PARP; and reduced FAS, FASL, and caspase-8 levels induced by BDE-47. In addition, troxerutin decreased the production of reactive oxygen species (ROS and increased the activities of antioxidative enzymes. Furthermore, troxerutin blunted Nrf2 ubiquitylation, enhanced the activity of Nrf2, decreased the activity of NOX2, and ameliorated kidney oxidant status of BDE-47-treated mice. Together, these results confirm that troxerutin could alleviate the cytotoxicity of BDE-47 through antioxidation and antiapoptosis, which suggests that its protective mechanism is involved in the inhibition of apoptosis via suppressing NOX2 activity and increasing Nrf2 signaling pathway.

  7. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages.

    Science.gov (United States)

    O'Toole, Timothy E; Zheng, Yu-Ting; Hellmann, Jason; Conklin, Daniel J; Barski, Oleg; Bhatnagar, Aruni

    2009-04-15

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca2+](i)), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca2+](I) with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca2+](I), leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure.

  8. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages

    International Nuclear Information System (INIS)

    O'Toole, Timothy E.; Zheng Yuting; Hellmann, Jason; Conklin, Daniel J.; Barski, Oleg; Bhatnagar, Aruni

    2009-01-01

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca 2+ ] i ), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca 2+ ] I with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca 2+ ] I , leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure.

  9. Increasing acidification of nonreplicating Lactococcus lactis Delta thyA mutants by incorporating ATPase activity

    DEFF Research Database (Denmark)

    Pedersen, Martin Bastian; Købmann, Brian Jensen; Jensen, Peter Ruhdal

    2002-01-01

    % of that of exponentially growing MBP71. However, when nonspecific ATPase activity was incorporated into MBP71, the lactic acid flux was restored to 100% but not above that point, indicating that control over the flux switched from ATP demand to ATP supply (i.e., to sugar transport and glycolysis). As determined by growing...... nonreplicating cells with high ATPase activity on various sugar sources, it appeared that glycolysis exerted the majority of the control. ATPase activity also stimulated the rate of acidification by noureplicating MBP71 growing in milk, and pH 5.2 was reached 40% faster than it was without ATPase activity. We...... concluded that ATPase activity is a functional means of increasing acidification by nonreplicating L. lactis....

  10. Apple, Cherry, and Blackcurrant Increases Nuclear Factor Kappa B Activation in Liver of Transgenic Mice

    DEFF Research Database (Denmark)

    Balstad, Trude; Paur, Ingvild; Poulsen, Morten

    2010-01-01

    Nuclear factor kappa B (NF-B) is essential in normal physiology, and several human disorders involve inappropriate regulation of NF-B. Diets dominated by plant-based foods protect against chronic diseases, and several food derived compounds have been identified as promising NF-B modulators. We...... investigated the effects of diets supplemented with apple, blackcurrant, or cherries on lipopolysaccharide (LPS)-induced NF-B activation in transgenic NF-B-luciferase mice. Whole body and organ specific NF-B activities were determined. The mice had ad libitum access to the respective experimental diets for 7...... slightly higher whole-body NF-B activation at 4 h, and all 3 experimental groups had higher NF-B activation at 6 h. LPS-induced NF-B activation in liver was increased with all 3 experimental diets, but no effects were observed in other organs. Our findings indicate that high intakes of lyophilized fruits...

  11. Increased premotor cortex activation in high functioning autism during action observation.

    Science.gov (United States)

    Perkins, Tom J; Bittar, Richard G; McGillivray, Jane A; Cox, Ivanna I; Stokes, Mark A

    2015-04-01

    The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Estimation of transient increases in bleeding risk associated with physical activity in children with haemophilia

    Directory of Open Access Journals (Sweden)

    Latimer Jane

    2008-06-01

    Full Text Available Abstract Background Although it is widely appreciated that vigorous physical activity can increase the risk of bleeding episodes in children with haemophilia, the magnitude of the increase in risk is not known. Accurate risk estimates could inform decisions made by children with haemophilia and their parents about participation in physical activity and aid the development of optimal prophylactic schedules. The aim of this study is to provide an accurate estimate of the risks of bleeding associated with vigorous physical activity in children with haemophilia. Methods/Design The study will be a case-crossover study nested within a prospective cohort study. Children with moderate or severe haemophilia A or B, recruited from two paediatric haematology departments in Australia, will participate in the study. The child, or the child's parent or guardian, will report bleeding episodes experienced over a 12-month period. Following a bleeding episode, the participant will be interviewed by telephone about exposures to physical activity in the case period (8 hours before the bleed and 2 control periods (an 8 hour period at the same time on the day preceding the bleed and an 8 hour period two days preceding the bleed. Conditional logistic regression will be used to estimate the risk of participating in vigorous physical activity from measures of exposure to physical activity in the case and control periods. Discussion This case-control study will provide estimates of the risk of participation in vigorous physical activity in children with haemophilia.

  13. Comparative Effectiveness of After-School Programs to Increase Physical Activity

    Directory of Open Access Journals (Sweden)

    Sabina B. Gesell

    2013-01-01

    Full Text Available Background. We conducted a comparative effectiveness analysis to evaluate the difference in the amount of physical activity children engaged in when enrolled in a physical activity-enhanced after-school program based in a community recreation center versus a standard school-based after-school program. Methods. The study was a natural experiment with 54 elementary school children attending the community ASP and 37 attending the school-based ASP. Accelerometry was used to measure physical activity. Data were collected at baseline, 6 weeks, and 12 weeks, with 91% retention. Results. At baseline, 43% of the multiethnic sample was overweight/obese, and the mean age was 7.9 years (SD = 1.7. Linear latent growth models suggested that the average difference between the two groups of children at Week 12 was 14.7 percentage points in moderate-vigorous physical activity (P<.001. Cost analysis suggested that children attending traditional school-based ASPs—at an average cost of $17.67 per day—would need an additional daily investment of $1.59 per child for 12 weeks to increase their moderate-vigorous physical activity by a model-implied 14.7 percentage points. Conclusions. A low-cost, alternative after-school program featuring adult-led physical activities in a community recreation center was associated with increased physical activity compared to standard-of-care school-based after-school program.

  14. Improvements in knee biomechanics during walking are associated with increased physical activity after total knee arthroplasty.

    Science.gov (United States)

    Arnold, John B; Mackintosh, Shylie; Olds, Timothy S; Jones, Sara; Thewlis, Dominic

    2015-12-01

    Total knee arthroplasty (TKA) in people with knee osteoarthritis increases knee-specific and general physical function, but it has not been established if there is a relationship between changes in these elements of functional ability. This study investigated changes and relationships between knee biomechanics during walking, physical activity, and use of time after TKA. Fifteen people awaiting TKA underwent 3D gait analysis before and six months after surgery. Physical activity and use of time were determined in free-living conditions from a high resolution 24-h activity recall. After surgery, participants displayed significant improvements in sagittal plane knee biomechanics and improved their physical activity profiles, standing for 105 more minutes (p=0.001) and performing 64 min more inside chores on average per day (p=0.008). Changes in sagittal plane knee range of motion (ROM) and peak knee flexion positively correlated with changes in total daily energy expenditure, time spent undertaking moderate to vigorous physical activity, inside chores and passive transport (r=0.52-0.66, p=0.005-0.047). Restoration of knee function occurs in parallel and is associated with improvements in physical activity and use of time after TKA. Increased functional knee ROM is required to support improvements in total and context specific physical activity. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. AM fungal exudates activate MAP kinases in plant cells in dependence from cytosolic Ca(2+) increase.

    Science.gov (United States)

    Francia, Doriana; Chiltz, Annick; Lo Schiavo, Fiorella; Pugin, Alain; Bonfante, Paola; Cardinale, Francesca

    2011-09-01

    The molecular dialogue occurring prior to direct contact between the fungal and plant partners of arbuscular-mycorrhizal (AM) symbioses begins with the release of fungal elicitors, so far only partially identified chemically, which can activate specific signaling pathways in the host plant. We show here that the activation of MAPK is also induced by exudates of germinating spores of Gigaspora margarita in cultured cells of the non-leguminous species tobacco (Nicotiana tabacum), as well as in those of the model legume Lotus japonicus. MAPK activity peaked about 15 min after the exposure of the host cells to the fungal exudates (FE). FE were also responsible for a rapid and transient increase in free cytosolic Ca(2+) in Nicotiana plumbaginifolia and tobacco cells, and pre-treatment with a Ca(2+)-channel blocker (La(3+)) showed that in these cells, MAPK activation was dependent on the cytosolic Ca(2+) increase. A partial dependence of MAPK activity on the common Sym pathway could be demonstrated for a cell line of L. japonicus defective for LjSym4 and hence unable to establish an AM symbiosis. Our results show that MAPK activation is triggered by an FE-induced cytosolic Ca(2+) transient, and that a Sym genetic determinant acts to modulate the intensity and duration of this activity. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. Equinoctial Activity Over Titan Dune Fields Revealed by Cassini/vims

    Science.gov (United States)

    Rodriguez, S.; Le Mouelic, S.; Barnes, J. W.; Hirtzig, M.; Rannou, P.; Sotin, C.; Brown, R. H.; Bow, J.; Vixie, G.; Cornet, T.; Bourgeois, O.; Narteau, C.; Courrech Du Pont, S.; Le Gall, A.; Reffet, E.; Griffith, C. A.; Jaumann, R.; Stephan, K.; Buratti, B. J.; Clark, R. N.; Baines, K. H.; Nicholson, P. D.; Coustenis, A.

    2012-12-01

    Titan, the largest satellite of Saturn, is the only satellite in the solar system with a dense atmosphere. The close and continuous observations of Titan by the Cassini spacecraft, in orbit around Saturn since July 2004, bring us evidences that Titan troposphere and low stratosphere experience an exotic, but complete meteorological cycle similar to the Earth hydrological cycle, with hydrocarbons evaporation, condensation in clouds, and rainfall. Cassini monitoring campaigns also demonstrate that Titan's cloud coverage and climate vary with latitude. Titan's tropics, with globally weak meteorological activity and widespread dune fields, seem to be slightly more arid than the poles, where extensive and numerous liquid reservoirs and sustained cloud activity have been discovered. Only a few tropo-spheric clouds have been observed at Titan's tropics during the southern summer. As equinox was approaching (in August 2009), they occurred more frequently and appeared to grow in strength and size. We present here the observation of intense brightening at Titan's tropics, very close to the equinox. These detections were conducted with the Visual and Infrared Mapping Spectrometer (VIMS) onboard Cassini. We will discuss the VIMS images of the three individual events detected so far, observed during the Titan's flybys T56 (22 May 2009), T65 (13 January 2010) and T70 (21 June 2010). T56, T65 and T70 observations show an intense and transient brighten-ing of large regions very close to the equator, right over the extensive dune fields of Senkyo, Belet and Shangri-La. They all appear spectrally and morphologically different from all transient surface features or atmospheric phenomena previously reported. Indeed, these events share in particular a strong brightening at wavelengths greater than 2 μm (especially at 5 μm), making them spectrally distinct from the small tropical clouds observed before the equinox and the large storms observed near the equator in September and October

  17. Creatine-induced activation of antioxidative defence in myotube cultures revealed by explorative NMR-based metabonomics and proteomics

    DEFF Research Database (Denmark)

    Young, Jette Feveile; Larsen, Lotte Bach; Malmendal, Anders

    2010-01-01

    Creatine is a key intermediate in energy metabolism and supplementation of creatine has been used for increasing muscle mass, strength and endurance. Creatine supplementation has also been reported to trigger the skeletal muscle expression of insulin like growth factor I, to increase the fat......-free mass and improve cognition in elderly, and more explorative approaches like transcriptomics has revealed additional information. The aim of the present study was to reveal additional insight into the biochemical effects of creatine supplementation at the protein and metabolite level by integrating...... the explorative techniques, proteomics and NMR metabonomics, in a systems biology approach. METHODS: Differentiated mouse myotube cultures (C2C12) were exposed to 5 mM creatine monohydrate (CMH) for 24 hours. For proteomics studies, lysed myotubes were analyzed in single 2-DGE gels where the first dimension...

  18. Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

    Energy Technology Data Exchange (ETDEWEB)

    Fyfe, Cameron D.; Grinter, Rhys; Josts, Inokentijs; Mosbahi, Khedidja [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Roszak, Aleksander W. [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Cogdell, Richard J.; Wall, Daniel M.; Burchmore, Richard J. S.; Byron, Olwyn; Walker, Daniel, E-mail: daniel.walker@glasgow.ac.uk [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom)

    2015-06-30

    The X-ray structure of protease-cleaved E. coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. Bacterial α-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli α-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli α-2-macroglobulin and human α-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group.

  19. Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

    International Nuclear Information System (INIS)

    Fyfe, Cameron D.; Grinter, Rhys; Josts, Inokentijs; Mosbahi, Khedidja; Roszak, Aleksander W.; Cogdell, Richard J.; Wall, Daniel M.; Burchmore, Richard J. S.; Byron, Olwyn; Walker, Daniel

    2015-01-01

    The X-ray structure of protease-cleaved E. coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. Bacterial α-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli α-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli α-2-macroglobulin and human α-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group

  20. Diagnosis and characterization of mania: Quantifying increased energy and activity in the human behavioral pattern monitor

    OpenAIRE

    Perry, William; McIlwain, Meghan; Kloezeman, Karen; Henry, Brook L.; Minassian, Arpi

    2016-01-01

    Increased energy or activity is now an essential feature of the mania of Bipolar Disorder (BD) according to DSM-5. This study examined whether objective measures of increased energy can differentiate manic BD individuals and provide greater diagnostic accuracy compared to rating scales, extending the work of previous studies with smaller samples. We also tested the relationship between objective measures of energy and rating scales. 50 hospitalized manic BD patients were compared to healthy s...

  1. Siderophile element concentrations in magnetic spherules from deep sea sediments revealed by instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Nogami, Ken-ichi; Shimamura, Tadashi; Tazawa, Yuji; Yamakoshi, Kazuo.

    1980-01-01

    For the purpose of deciding the extraterrestrial origin of the magnetic spherules found in deep sea sediments, the siderophile elements Co, Ni, Ir and/or Au etc., were measured by instrumental neutron activation analysis. Spherules were collected from red clay samples which were dredged from Mid Pacific Ocean. Only spherules which had smooth surfaces and relatively high specific gravities were chosen for analysis. Existence of Co, Ni and Ir in most spherules suggests the possibility of an extraterrestrial origin for these spherules. It is not clear whether these spherules are droplets ablated from iron meteorites entering into the Earth's atmosphere or they are cosmic iron grains themselves. X-ray diffraction analysis suggested that these spherules are the products of rapid cooling materials. (author)

  2. Sealing process with calcite in the Nojima active fault zone revealed from isotope analysis of calcite

    International Nuclear Information System (INIS)

    Arai, Takashi; Tsukahara, Hiroaki; Morikiyo, Toshiro

    2003-01-01

    The Nojima fault appeared on the surface in the northern part of Awaji Island, central Japan as a result of the Hyogo-ken Nanbu earthquake (1995, M=7.2). Active fault drilling was performed by the Disaster Prevention Research Institute (DPRI), Kyoto University, and core samples were retrieved from 1410 to 1710 m, which were composed of intact and fractured granodiorites. We obtained calcite samples and gas samples from the vein in marginal fracture and non-fracture zones. We analyzed the carbon and oxygen isotope ratios of calcite and carbon dioxide to investigate the characteristic isotope ratios of fluids in the active fault zone, to estimate the origins of fluids, and to determine the sealing process of fractures. The analyzed values of carbon and oxygen isotope ratios of calcite were -10.3 to -7.2 per mille, 18 to 23 per mille, respectively, and carbon isotope ratios of CO 2 were -21 to -17 per mille. If carbon isotope ratios of calcite were at equilibrium with those of CO 2 , the precipitation temperature of calcite is calculated to be 30 to 50 deg C. This temperature is consistent with the present temperature of the depth where drilling cores were retrieved. Oxygen isotope ratios of H 2 O that, precipitated calcite were calculated to be -1.8 to -5.5 per mille. These values indicate calcite were precipitated from mixed fluids of sea water and meteoric water. Therefore, the marginal fracture zone of the Nojima fault was sealed with calcite, which was generated from mixing of sea water and meteoric water in situ. (author)

  3. Increased SBPase activity improves photosynthesis and grain yield in wheat grown in greenhouse conditions.

    Science.gov (United States)

    Driever, Steven M; Simkin, Andrew J; Alotaibi, Saqer; Fisk, Stuart J; Madgwick, Pippa J; Sparks, Caroline A; Jones, Huw D; Lawson, Tracy; Parry, Martin A J; Raines, Christine A

    2017-09-26

    To meet the growing demand for food, substantial improvements in yields are needed. This is particularly the case for wheat, where global yield has stagnated in recent years. Increasing photosynthesis has been identified as a primary target to achieve yield improvements. To increase leaf photosynthesis in wheat, the level of the Calvin-Benson cycle enzyme sedoheptulose-1,7-biphosphatase (SBPase) has been increased through transformation and expression of a Brachypodium distachyon SBPase gene construct. Transgenic lines with increased SBPase protein levels and activity were grown under greenhouse conditions and showed enhanced leaf photosynthesis and increased total biomass and dry seed yield. This showed the potential of improving yield potential by increasing leaf photosynthesis in a crop species such as wheat. The results are discussed with regard to future strategies for further improvement of photosynthesis in wheat.This article is part of the themed issue 'Enhancing photosynthesis in crop plants: targets for improvement'. © 2017 The Authors.

  4. Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions

    Directory of Open Access Journals (Sweden)

    Benedito M.A.C.

    2001-01-01

    Full Text Available Some upper brainstem cholinergic neurons (pedunculopontine and laterodorsal tegmental nuclei are involved in the generation of rapid eye movement (REM sleep and project rostrally to the thalamus and caudally to the medulla oblongata. A previous report showed that 96 h of REM sleep deprivation in rats induced an increase in the activity of brainstem acetylcholinesterase (Achase, the enzyme which inactivates acetylcholine (Ach in the synaptic cleft. There was no change in the enzyme's activity in the whole brain and cerebrum. The components of the cholinergic synaptic endings (for example, Achase are not uniformly distributed throughout the discrete regions of the brain. In order to detect possible regional changes we measured Achase activity in several discrete rat brain regions (medulla oblongata, pons, thalamus, striatum, hippocampus and cerebral cortex after 96 h of REM sleep deprivation. Naive adult male Wistar rats were deprived of REM sleep using the flower-pot technique, while control rats were left in their home cages. Total, membrane-bound and soluble Achase activities (nmol of thiocholine formed min-1 mg protein-1 were assayed photometrically. The results (mean ± SD obtained showed a statistically significant (Student t-test increase in total Achase activity in the pons (control: 147.8 ± 12.8, REM sleep-deprived: 169.3 ± 17.4, N = 6 for both groups, P<0.025 and thalamus (control: 167.4 ± 29.0, REM sleep-deprived: 191.9 ± 15.4, N = 6 for both groups, P<0.05. Increases in membrane-bound Achase activity in the pons (control: 171.0 ± 14.7, REM sleep-deprived: 189.5 ± 19.5, N = 6 for both groups, P<0.05 and soluble enzyme activity in the medulla oblongata (control: 147.6 ± 16.3, REM sleep-deprived: 163.8 ± 8.3, N = 6 for both groups, P<0.05 were also observed. There were no statistically significant differences in the enzyme's activity in the other brain regions assayed. The present findings show that the increase in Achase activity

  5. Alkalosis and Dialytic Clearance of Phosphate Increases Phosphatase Activity: A Hidden Consequence of Hemodialysis.

    Directory of Open Access Journals (Sweden)

    Ricardo Villa-Bellosta

    Full Text Available Extracellular pyrophosphate is a potent endogenous inhibitor of vascular calcification, which is degraded by alkaline phosphatase (ALP and generated by hydrolysis of ATP via ectonucleotide pyrophosphatase/phosphodiesterase 1 (eNPP1. ALP activity (as routinely measured in clinical practice represents the maximal activity (in ideal conditions, but not the real activity (in normal or physiological conditions. For the first time, the present study investigated extracellular pyrophosphate metabolism during hemodialysis sessions (including its synthesis via eNPP1 and its degradation via ALP in physiological conditions.45 patients in hemodialysis were studied. Physiological ALP activity represents only 4-6% of clinical activity. ALP activity increased post-hemodialysis by 2% under ideal conditions (87.4 ± 3.3 IU/L vs. 89.3 ± 3.6 IU/L and 48% under physiological conditions (3.5 ± 0.2 IU/L vs. 5.2 ± 0.2 IU/L. Pyrophosphate synthesis by ATP hydrolysis remained unaltered post-hemodialysis. Post-hemodialysis plasma pH (7.45 ± 0.02 significantly increased compared with the pre-dialysis pH (7.26 ± 0.02. The slight variation in pH (~0.2 units induced a significant increase in ALP activity (9%. Addition of phosphate in post-hemodialysis plasma significantly decreased ALP activity, although this effect was not observed with the addition of urea. Reduction in phosphate levels and increment in pH were significantly associated with an increase in physiological ALP activity post-hemodialysis. A decrease in plasma pyrophosphate levels (3.3 ± 0.3 μmol/L vs. 1.9 ± 0.1 μmol/L and pyrophosphate/ATP ratio (1.9 ± 0.2 vs. 1.4 ± 0.1 post-hemodialysis was also observed.Extraction of uremic toxins, primarily phosphate and hydrogen ions, dramatically increases the ALP activity under physiological conditions. This hitherto unknown consequence of hemodialysis suggests a reinterpretation of the clinical value of this parameter.

  6. Reactive oxygen species mediate TNFR1 increase after TRPV1 activation in mouse DRG neurons

    Directory of Open Access Journals (Sweden)

    Westlund Karin N

    2009-06-01

    Full Text Available Abstract Background Transient receptor potential vanilloid subtype 1 (TRPV1 is activated by low pH/protons and is well known to be involved in hyperalgesia during inflammation. Tumor necrosis factor α (TNF-α, a proinflammatory cytokine, is involved in nociceptive responses causing hyperalgesia through TNF receptor type 1 (TNFR1 activation. Reactive oxygen species (ROS production is also prominently increased in inflamed tissue. The present study investigated TNFR1 receptors in primary cultured mouse dorsal root ganglion (DRG neurons after TRPV1 activation and the involvement of ROS. C57BL/6 mice, both TRPV1 knockout and wild type, were used for immunofluorescent and live cell imaging. The L4 and L5 DRGs were dissected bilaterally and cultured overnight. TRPV1 was stimulated with capsaicin or its potent analog, resiniferatoxin. ROS production was measured with live cell imaging and TNFR1 was detected with immunofluorescence in DRG primary cultures. The TRPV1 knockout mice, TRPV1 antagonist, capsazepine, and ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN, were employed to explore the functional relationship among TRPV1, ROS and TNFR1 in these studies. Results The results demonstrate that TRPV1 activation increases TNFR1 receptors and ROS generation in primary cultures of mouse DRG neurons. Activated increases in TNFR1 receptors and ROS production are absent in TRPV1 deficient mice. The PBN blocks increases in TNFR1 and ROS production induced by capsaicin/resiniferatoxin. Conclusion TRPV1 activation increases TNFR1 in cultured mouse DRG neurons through a ROS signaling pathway, a novel sensitization mechanism in DRG neurons.

  7. Optogenetic Inhibition Reveals Distinct Roles for Basolateral Amygdala Activity at Discrete Time Points during Risky Decision Making.

    Science.gov (United States)

    Orsini, Caitlin A; Hernandez, Caesar M; Singhal, Sarthak; Kelly, Kyle B; Frazier, Charles J; Bizon, Jennifer L; Setlow, Barry

    2017-11-29

    Decision making is a multifaceted process, consisting of several distinct phases that likely require different cognitive operations. Previous work showed that the basolateral amygdala (BLA) is a critical substrate for decision making involving risk of punishment; however, it is unclear how the BLA is recruited at different stages of the decision process. To this end, the current study used optogenetics to inhibit the BLA during specific task phases in a model of risky decision making (risky decision-making task) in which rats choose between a small, "safe" reward and a large reward accompanied by varying probabilities of footshock punishment. Male Long-Evans rats received intra-BLA microinjections of viral vectors carrying either halorhodopsin (eNpHR3.0-mCherry) or mCherry alone (control) followed by optic fiber implants and were trained in the risky decision-making task. Laser delivery during the task occurred during intertrial interval, deliberation, or reward outcome phases, the latter of which was further divided into the three possible outcomes (small, safe; large, unpunished; large, punished). Inhibition of the BLA selectively during the deliberation phase decreased choice of the large, risky outcome (decreased risky choice). In contrast, BLA inhibition selectively during delivery of the large, punished outcome increased risky choice. Inhibition had no effect during the other phases, nor did laser delivery affect performance in control rats. Collectively, these data indicate that the BLA can either inhibit or promote choice of risky options, depending on the phase of the decision process in which it is active. SIGNIFICANCE STATEMENT To date, most behavioral neuroscience research on neural mechanisms of decision making has used techniques that preclude assessment of distinct phases of the decision process. Here we show that optogenetic inhibition of the BLA has opposite effects on choice behavior in a rat model of risky decision making, depending on the phase

  8. Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Mengwen Qi

    2018-02-01

    Full Text Available Background/Aims: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4 is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Methods: Whole-cell patch clamp recording was employed to record glycine-activated current (IGly and Western blot was conducted to assess GlyRs subunits protein expression. Results: Application of TRPV4 agonist (GSK1016790A or 5,6-EET increased IGly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047 and GlyR (strychnine, indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in IGly was significantly attenuated by protein kinase C (PKC (BIM II or D-sphingosine or calcium/calmodulin-dependent protein kinase II (CaMKII (KN-62 or KN-93 antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv. injected with GSK1016790A for 5 d. Conclusion: Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in IGly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission.

  9. Circadian rhythm of elemental concentration in Japanese morning-glory revealed by neutron activation analysis

    International Nuclear Information System (INIS)

    Kobayashi, N.I.; Tanoi, K.; Nakanishi, T.M.

    2007-01-01

    Elemental concentration in each tissue of Japanese morning-glory (Pharbitis nil) during the growth was analyzed by INAA. Plants were grown in water culture for 4 days under 12-hour light and 12-hour dark condition. During the growth, 10 plants in the same developmental stage were periodically harvested. Then the plants were separated into 9 tissues to determine elemental concentration and water content. There was an elemental specific profile within the plant tissue, for example, Na and K concentrations were high in root whereas Mg and Ca concentrations were high at the upper part of the plants. Among the elements studied, Ca and Mg showed rhythmical change in concentration, increased during the day and decreased during the night. This tendency was especially noted at shoot apex. However, water content in all of the tissue was increased about 6 hours prior to the light period and showed maximum in the middle of the light period. About 6 hour difference of water content movement to those of Ca and Mg concentration suggested that water movement drives more dynamic change of each elemental concentration within a plant. (author)

  10. Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine

    DEFF Research Database (Denmark)

    Leke, Renata; Bak, Lasse Kristoffer; Anker, Malene

    2011-01-01

    Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme....... Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia. The aim of this study was to characterize the ammonia-detoxifying mechanisms as well as the effects of ammonia on energy-generating metabolic pathways...... in a mouse neuronal-astrocytic co-culture model of the GABAergic system. We found that 5 mM ammonium chloride affected energy metabolism by increasing the neuronal TCA cycle activity and switching the astrocytic TCA cycle toward synthesis of substrate for glutamine synthesis. Furthermore, ammonia exposure...

  11. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    International Nuclear Information System (INIS)

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

    2011-01-01

    Highlights: → Nerve transection increased Notch signaling in paralyzed muscle. → Nandrolone prevented denervation-induced Notch signaling. → Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. → Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  12. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  13. Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats.

    Science.gov (United States)

    Teodorak, Brena P; Ferreira, Gabriela K; Scaini, Giselli; Wessler, Letícia B; Heylmann, Alexandra S; Deroza, Pedro; Valvassori, Samira S; Zugno, Alexandra I; Quevedo, João; Streck, Emilio L

    2015-08-01

    Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p.) or vehicle (2% Tween 80). Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.

  14. Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats

    Directory of Open Access Journals (Sweden)

    BRENA P. TEODORAK

    2015-08-01

    Full Text Available Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p. or vehicle (2% Tween 80. Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.

  15. rTMS Induced Tinnitus Relief Is Related to an Increase in Auditory Cortical Alpha Activity

    Science.gov (United States)

    Müller, Nadia; Lorenz, Isabel; Langguth, Berthold; Weisz, Nathan

    2013-01-01

    Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom. A promising approach for the treatment of tinnitus is repetitive transcranial magnetic stimulation (rTMS) as this directly affects tinnitus-related brain activity. Several studies indeed show tinnitus relief after rTMS, however effects are moderate and vary strongly across patients. This may be due to a lack of knowledge regarding how rTMS affects oscillatory activity in tinnitus sufferers and which modulations are associated with tinnitus relief. In the present study we examined the effects of five different stimulation protocols (including sham) by measuring tinnitus loudness and tinnitus-related brain activity with Magnetoencephalography before and after rTMS. Changes in oscillatory activity were analysed for the stimulated auditory cortex as well as for the entire brain regarding certain frequency bands of interest (delta, theta, alpha, gamma). In line with the literature the effects of rTMS on tinnitus loudness varied strongly across patients. This variability was also reflected in the rTMS effects on oscillatory activity. Importantly, strong reductions in tinnitus loudness were associated with increases in alpha power in the stimulated auditory cortex, while an unspecific decrease in gamma and alpha power, particularly in left frontal regions, was linked to an increase in tinnitus loudness. The identification of alpha power increase as main correlate for tinnitus reduction sheds further light on the pathophysiology of tinnitus. This will hopefully stimulate the development of more effective therapy approaches. PMID:23390539

  16. Open source data reveals connection between online and on-street protest activity.

    Science.gov (United States)

    Qi, Hong; Manrique, Pedro; Johnson, Daniela; Restrepo, Elvira; Johnson, Neil F

    There is enormous interest in inferring features of human behavior in the real world from potential digital footprints created online - particularly at the collective level, where the sheer volume of online activity may indicate some changing mood within the population regarding a particular topic. Civil unrest is a prime example, involving the spontaneous appearance of large crowds of otherwise unrelated people on the street on a certain day. While indicators of brewing protests might be gleaned from individual online communications or account content (e.g. Twitter, Facebook) societal concerns regarding privacy can make such probing a politically delicate issue. Here we show that instead, a simple low-level indicator of civil unrest can be obtained from online data at the aggregate level through Google Trends or similar tools. Our study covers countries across Latin America during 2011-2014 in which diverse civil unrest events took place. In each case, we find that the combination of the volume and momentum of searches from Google Trends surrounding pairs of simple keywords, tailored for the specific cultural setting, provide good indicators of periods of civil unrest. This proof-of-concept study motivates the search for more geographically specific indicators based on geo-located searches at the urban level.

  17. Neural activity in the medial temporal lobe reveals the fidelity of mental time travel.

    Science.gov (United States)

    Kragel, James E; Morton, Neal W; Polyn, Sean M

    2015-02-18

    Neural circuitry in the medial temporal lobe (MTL) is critically involved in mental time travel, which involves the vivid retrieval of the details of past experience. Neuroscientific theories propose that the MTL supports memory of the past by retrieving previously encoded episodic information, as well as by reactivating a temporal code specifying the position of a particular event within an episode. However, the neural computations supporting these abilities are underspecified. To test hypotheses regarding the computational mechanisms supported by different MTL subregions during mental time travel, we developed a computational model that linked a blood oxygenation level-dependent signal to cognitive operations, allowing us to predict human performance in a memory search task. Activity in the posterior MTL, including parahippocampal cortex, reflected how strongly one reactivates the temporal context of a retrieved memory, allowing the model to predict whether the next memory will correspond to a nearby moment in the study episode. A signal in the anterior MTL, including perirhinal cortex, indicated the successful retrieval of list items, without providing information regarding temporal organization. A hippocampal signal reflected both processes, consistent with theories that this region binds item and context information together to form episodic memories. These findings provide evidence for modern theories that describe complementary roles of the hippocampus and surrounding parahippocampal and perirhinal cortices during the retrieval of episodic memories, shaping how humans revisit the past. Copyright © 2015 the authors 0270-6474/15/352914-13$15.00/0.

  18. Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus

    Directory of Open Access Journals (Sweden)

    Keiko Rausch

    2017-01-01

    Full Text Available Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from infection with receptor tyrosine kinase inhibitors, while placental-derived cells that lack AXL expression are insensitive to this inhibition. Importantly, we identified nanchangmycin as a potent inhibitor of Zika virus entry across all cell types tested, including physiologically relevant primary cells. Nanchangmycin also was active against other medically relevant viruses, including West Nile, dengue, and chikungunya viruses that use a similar route of entry. This study provides a resource of small molecules to study Zika virus pathogenesis.

  19. Revealing Physical Activity of GRB Central Engine with Macronova/Kilonova Data

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Zhao-Qiang; Jin, Zhi-Ping; Liang, Yun-Feng; Li, Xiang; Fan, Yi-Zhong; Wei, Da-Ming, E-mail: yzfan@pmo.ac.cn, E-mail: dmwei@pmo.ac.cn [Key Laboratory of dark Matter and Space Astronomy, Purple Mountain Observatory, Chinese Academy of Science, Nanjing 210008 (China)

    2017-02-01

    The modeling of Li-Paczyński macronova/kilonova signals gives a reasonable estimate on the neutron-rich material ejected during the neutron star mergers. Usually the accretion disk is more massive than the macronova ejecta, with which the efficiencies of converting the disk mass into prompt emission of three merger-driven GRBs can hence be directly constrained. Supposing the macronovae/kilonovae associated with GRB 050709, GRB 060614, and GRB 130603B arose from radioactive decay of the r -process material, the upper limit on energy conversion efficiencies are found to be as low as ∼10{sup −6}–10{sup −4}. Moreover, for all three events, neutrino annihilation is likely powerful enough to account for the brief gamma-ray flashes. Neutrino annihilation can also explain the “extended” emission lasting ∼100 s in GRB 050709, but does not work for the one in GRB 060614. These progresses demonstrate that the macronova can serve as a novel probe of the central engine activity.

  20. A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria.

    Science.gov (United States)

    Jen, Freda E-C; Djoko, Karrera Y; Bent, Stephen J; Day, Christopher J; McEwan, Alastair G; Jennings, Michael P

    2015-09-01

    Under conditions of low oxygen availability, Neisseria meningitidis and Neisseria gonorrhoeae are able to respire via a partial denitrification pathway in which nitrite is converted to nitrous oxide. In this process, nitrite reductase (AniA), a copper (Cu)-containing protein converts nitrite to NO, and this product is converted to nitrous oxide by nitric oxide reductase (NorB). NorB also confers protection against toxic NO, and so we devised a conditional lethal screen, using a norB mutant, to identify mutants that were resistant to nitrite-dependent killing. After random-deletion mutagenesis of N. meningitidis, this genetic screen identified a gene encoding a Cu chaperone that is essential for AniA function, AccA. Purified AccA binds one Cu (I) ion and also possesses a second binding site for Cu (II). This novel periplasmic Cu chaperone (AccA) appears to be essential for provision of Cu ions to AniA of pathogenic Neisseria to generate an active nitrite reductase. Apart from the Neisseria genus, AccA is distributed across a wide range of environmental Proteobacteria species. © FASEB.

  1. Microarray Analysis Reveals the Molecular Basis of Antiarthritic Activity of Huo-Luo-Xiao-Ling Dan

    Directory of Open Access Journals (Sweden)

    Hua Yu

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease of autoimmune origin. Huo-luo-xiao-ling dan (HLXL is an herbal mixture that has been used in traditional Chinese medicine over several decades to treat chronic inflammatory diseases including RA. However, the mechanism of the anti-arthritic action of this herbal remedy is poorly understood at the molecular level. In this study, we determined by microarray analysis the effects of HLXL on the global gene expression profile of the draining lymph node cells (LNC in the rat adjuvant arthritis (AA model of human RA. In LNC restimulated in vitro with the disease-related antigen mycobacterial heat-shock protein 65 (Bhsp65, 84 differentially expressed genes (DEG (64 upregulated and 20 downregulated versus 120 DEG (94 upregulated and 26 downregulated were identified in HLXL-treated versus vehicle (Water-treated rats, respectively, and 62 DEG (45 upregulated and 17 downregulated were shared between the two groups. The most affected pathways in response to HLXL treatment included immune response, inflammation, cellular proliferation and apoptosis, and metabolic processes, many of which are directly relevant to arthritis pathogenesis. These results would advance our understanding of the mechanisms underlying the anti-arthritic activity of HLXL.

  2. Mass spectrometry footprinting reveals the structural rearrangements of cyanobacterial orange carotenoid protein upon light activation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Haijun [Washington University; Zhang, Hao [Washington University; King, Jeremy D. [Washington University; Wolf, Nathan R. [Washington University; Prado, Mindy [Washington University; Gross, Michael L. [Washington University; Blankenship, Robert E. [Washington University

    2014-12-01

    The orange carotenoid protein (OCP), a member of the family of blue light photoactive proteins, is required for efficient photoprotection in many cyanobacteria. Photoexcitation of the carotenoid in the OCP results in structural changes within the chromophore and the protein to give an active red form of OCP that is required for phycobilisome binding and consequent fluorescence quenching. We characterized the light-dependent structural changes by mass spectrometry-based carboxyl footprinting and found that an α helix in the N-terminal extension of OCP plays a key role in this photoactivation process. Although this helix is located on and associates with the outside of the β-sheet core in the C-terminal domain of OCP in the dark, photoinduced changes in the domain structure disrupt this interaction. We propose that this mechanism couples light-dependent carotenoid conformational changes to global protein conformational dynamics in favor of functional phycobilisome binding, and is an essential part of the OCP photocycle.

  3. Comparative analysis of carbohydrate active enzymes in Clostridium termitidis CT1112 reveals complex carbohydrate degradation ability.

    Directory of Open Access Journals (Sweden)

    Riffat I Munir

    Full Text Available Clostridium termitidis strain CT1112 is an anaerobic, gram positive, mesophilic, cellulolytic bacillus isolated from the gut of the wood-feeding termite, Nasutitermes lujae. It produces biofuels such as hydrogen and ethanol from cellulose, cellobiose, xylan, xylose, glucose, and other sugars, and therefore could be used for biofuel production from biomass through consolidated bioprocessing. The first step in the production of biofuel from biomass by microorganisms is the hydrolysis of complex carbohydrates present in biomass. This is achieved through the presence of a repertoire of secreted or complexed carbohydrate active enzymes (CAZymes, sometimes organized in an extracellular organelle called cellulosome. To assess the ability and understand the mechanism of polysaccharide hydrolysis in C. termitidis, the recently sequenced strain CT1112 of C. termitidis was analyzed for both CAZymes and cellulosomal components, and compared to other cellulolytic bacteria. A total of 355 CAZyme sequences were identified in C. termitidis, significantly higher than other Clostridial species. Of these, high numbers of glycoside hydrolases (199 and carbohydrate binding modules (95 were identified. The presence of a variety of CAZymes involved with polysaccharide utilization/degradation ability suggests hydrolysis potential for a wide range of polysaccharides. In addition, dockerin-bearing enzymes, cohesion domains and a cellulosomal gene cluster were identified, indicating the presence of potential cellulosome assembly.

  4. Repetition-related reductions in neural activity reveal component processes of mental simulation.

    Science.gov (United States)

    Szpunar, Karl K; St Jacques, Peggy L; Robbins, Clifford A; Wig, Gagan S; Schacter, Daniel L

    2014-05-01

    In everyday life, people adaptively prepare for the future by simulating dynamic events about impending interactions with people, objects and locations. Previous research has consistently demonstrated that a distributed network of frontal-parietal-temporal brain regions supports this ubiquitous mental activity. Nonetheless, little is known about the manner in which specific regions of this network contribute to component features of future simulation. In two experiments, we used a functional magnetic resonance (fMR)-repetition suppression paradigm to demonstrate that distinct frontal-parietal-temporal regions are sensitive to processing the scenarios or what participants imagined was happening in an event (e.g., medial prefrontal, posterior cingulate, temporal-parietal and middle temporal cortices are sensitive to the scenarios associated with future social events), people (medial prefrontal cortex), objects (inferior frontal and premotor cortices) and locations (posterior cingulate/retrosplenial, parahippocampal and posterior parietal cortices) that typically constitute simulations of personal future events. This pattern of results demonstrates that the neural substrates of these component features of event simulations can be reliably identified in the context of a task that requires participants to simulate complex, everyday future experiences.

  5. Novel activities by ebolavirus and marburgvirus interferon antagonists revealed using a standardized in vitro reporter system.

    Science.gov (United States)

    Guito, Jonathan C; Albariño, César G; Chakrabarti, Ayan K; Towner, Jonathan S

    2017-01-15

    Filoviruses are highly lethal in humans and nonhuman primates, likely due to potent antagonism of host interferon (IFN) responses early in infection. Filoviral protein VP35 is implicated as the major IFN induction antagonist, while Ebola virus (EBOV) VP24 or Marburg virus (MARV) VP40 are known to block downstream IFN signaling. Despite progress elucidating EBOV and MARV antagonist function, those for most other filoviruses, including Reston (RESTV), Sudan (SUDV), Taï Forest (TAFV), Bundibugyo (BDBV) and Ravn (RAVV) viruses, remain largely neglected. Thus, using standardized vectors and reporter assays, we characterized activities by each IFN antagonist from all known ebolavirus and marburgvirus species side-by-side. We uncover noncanonical suppression of IFN induction by ebolavirus VP24, differing potencies by MARV and RAVV proteins, and intriguingly, weaker antagonism by VP24 of RESTV. These underlying molecular explanations for differential virulence in humans could guide future investigations of more-neglected filoviruses as well as treatment and vaccine studies. Published by Elsevier Inc.

  6. Digital quantification of gene expression in sequential breast cancer biopsies reveals activation of an immune response.

    Directory of Open Access Journals (Sweden)

    Rinath M Jeselsohn

    Full Text Available Advancements in molecular biology have unveiled multiple breast cancer promoting pathways and potential therapeutic targets. Large randomized clinical trials remain the ultimate means of validating therapeutic efficacy, but they require large cohorts of patients and are lengthy and costly. A useful approach is to conduct a window of opportunity study in which patients are exposed to a drug pre-surgically during the interval between the core needle biopsy and the definitive surgery. These are non-therapeutic studies and the end point is not clinical or pathological response but rather evaluation of molecular changes in the tumor specimens that can predict response. However, since the end points of the non-therapeutic studies are biologic, it is critical to first define the biologic changes that occur in the absence of treatment. In this study, we compared the molecular profiles of breast cancer tumors at the time of the diagnostic biopsy versus the definitive surgery in the absence of any intervention using the Nanostring nCounter platform. We found that while the majority of the transcripts did not vary between the two biopsies, there was evidence of activation of immune related genes in response to the first biopsy and further investigations of the immune changes after a biopsy in early breast cancer seem warranted.

  7. Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures

    International Nuclear Information System (INIS)

    Oyama, Takuji; Toyota, Kenji; Waku, Tsuyoshi; Hirakawa, Yuko; Nagasawa, Naoko; Kasuga, Jun-ichi; Hashimoto, Yuichi; Miyachi, Hiroyuki; Morikawa, Kosuke

    2009-01-01

    The structures of the ligand-binding domains (LBDs) of human peroxisome proliferator-activated receptors (PPARα, PPARγ and PPARδ) in complexes with a pan agonist, an α/δ dual agonist and a PPARδ-specific agonist were determined. The results explain how each ligand is recognized by the PPAR LBDs at an atomic level. Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family, which is defined as transcriptional factors that are activated by the binding of ligands to their ligand-binding domains (LBDs). Although the three PPAR subtypes display different tissue distribution patterns and distinct pharmacological profiles, they all are essentially related to fatty-acid and glucose metabolism. Since the PPARs share similar three-dimensional structures within the LBDs, synthetic ligands which simultaneously activate two or all of the PPARs could be potent candidates in terms of drugs for the treatment of abnormal metabolic homeostasis. The structures of several PPAR LBDs were determined in complex with synthetic ligands, derivatives of 3-(4-alkoxyphenyl)propanoic acid, which exhibit unique agonistic activities. The PPARα and PPARγ LBDs were complexed with the same pan agonist, TIPP-703, which activates all three PPARs and their crystal structures were determined. The two LBD–ligand complex structures revealed how the pan agonist is adapted to the similar, but significantly different, ligand-binding pockets of the PPARs. The structures of the PPARδ LBD in complex with an α/δ-selective ligand, TIPP-401, and with a related δ-specific ligand, TIPP-204, were also determined. The comparison between the two PPARδ complexes revealed how each ligand exhibits either a ‘dual selective’ or ‘single specific’ binding mode

  8. Alpha-Amylase Activity in Blood Increases after Pharmacological, But Not Psychological, Activation of the Adrenergic System.

    Directory of Open Access Journals (Sweden)

    Urs M Nater

    Full Text Available Alpha-amylase in both blood and saliva has been used as a diagnostic parameter. While studies examining alpha-amylase activity in saliva have shown that it is sensitive to physiological and psychological challenge of the adrenergic system, no challenge studies have attempted to elucidate the role of the adrenergic system in alpha-amylase activity in blood. We set out to examine the impact of psychological and pharmacological challenge on alpha-amylase in blood in two separate studies.In study 1, healthy subjects were examined in a placebo-controlled, double-blind paradigm using yohimbine, an alpha2-adrenergic antagonist. In study 2, subjects were examined in a standardized rest-controlled psychosocial stress protocol. Alpha-amylase activity in blood was repeatedly measured in both studies.Results of study 1 showed that alpha-amylase in blood is subject to stronger increases after injection of yohimbine compared to placebo. In study 2, results showed that there was no significant effect of psychological stress compared to rest.Alpha-amylase in blood increases after pharmacological activation of the adrenergic pathways suggesting that sympathetic receptors are responsible for these changes. Psychological stress, however, does not seem to have an impact on alpha-amylase in blood. Our findings provide insight into the mechanisms underlying activity changes in alpha-amylase in blood in healthy individuals.

  9. Decreasing Sports Activity with Increasing Age? Findings from a 20-Year Longitudinal and Cohort Sequence Analysis

    Science.gov (United States)

    Breuer, Christoph; Wicker, Pamela

    2009-01-01

    According to cross-sectional studies in sport science literature, decreasing sports activity with increasing age is generally assumed. In this paper, the validity of this assumption is checked by applying more effective methods of analysis, such as longitudinal and cohort sequence analyses. With the help of 20 years' worth of data records from the…

  10. Increase in Operator's Sympathetic Nerve Activity during Complicated Hepatobiliary Surgery: Evidence for Surgeons' Mental Stress.

    Science.gov (United States)

    Yamanouchi, Kosho; Hayashida, Naomi; Kuba, Sayaka; Sakimura, Chika; Kuroki, Tamotsu; Togo, Michita; Katayama, Noritada; Takamura, Noboru; Eguchi, Susumu

    2015-11-01

    Surgeons often experience stress during operations. The heart rate variability (HRV) is the variability in the beat-to-beat interval, which has been used as parameters of stress. The purpose of this study was to evaluate mental stress of surgeons before, during and after operations, especially during pancreaticoduodenectomy (PD) and living donor liver transplantation (LDLT). Additionally, the parameters were compared in various procedures during the operations. By frequency domain method using electrocardiograph, we measured the high frequency (HF) component, representing the parasympathetic activity, and the low frequency (LF)/HF ratio, representing the sympathetic activity. In all 5 cases of PD, the surgeon showed significantly lower HF component and higher LF/HF during operation, indicating predominance of sympathetic nervous system and increased stress, than those before the operation (p operation. Out of the 4 LDLT cases, the value of HF was decreased in two and the LF/HF increased in three cases (p operation compared to those before the operation. In all cases, the value of HF was decreased and/or the LF/HF increased significantly during the reconstruction of the vessels or bile ducts than during the removal of the liver. Thus, sympathetic nerve activity increased during hepatobiliary surgery compared with the level before the operation, and various procedures during the operations induced diverse changes in the autonomic nervous activities. The HRV analysis could assess the chronological changes of mental stress by measuring the autonomic nervous balances.

  11. Increase in natural killer cell activity during diethylcarbamazine treatment of patients with filariasis

    DEFF Research Database (Denmark)

    Pedersen, B K; Bygbjerg, Ib Christian; Svenson, M

    1987-01-01

    Two patients, one with Bancroftian filariasis and the other with onchocerciasis, and two healthy controls were treated with diethylcarbamazine (DEC). The natural killer (NK) cell activity of the two patients increased during DEC treatment to 2.5 and 2.8 times, respectively, while that of the cont...

  12. Effects of increasing use of trifluralin and glyphosate on the microbial activity of a lea soil

    International Nuclear Information System (INIS)

    Barros, Edna Santos de; Monteiro, Regina Teresa Rosim; Peixoto, Maria de Fatima da Silva Pinto; Fay, Elizabeth Francisconi

    1997-01-01

    This work considers the importance of the glyphosate and trifluralin, which are the most used herbicides by the brazilian plantations, applying approximately fifteen and nine millions of liters by crop, respectively, for the evaluation of the increasing use of these herbicides effects on the microbial activity of a lea soil which are used for beans cultivation

  13. Increasing physical activity in patients with mental illness--A randomized controlled trial.

    Science.gov (United States)

    Göhner, Wiebke; Dietsche, Christine; Fuchs, Reinhard

    2015-11-01

    The objective of the study was to evaluate whether a motivational-volitional intervention program offered in addition to an existing sport program during stationary treatment is capable of establishing a post-stationary increase in physical activity in persons with mental illness. N=112 in-patients were initially randomly assigned to the control group (CG; standard rehabilitation) or intervention group (IG; standard rehabilitation plus intervention). Assessments were conducted at four measurement points. At 6 months follow up, the level of exercise in the IG was 95 min/week higher than in the CG (p=.02). The participants of the IG were able to increase their level of goal intention until 6 months follow up (t2: p=.03; t4: p=.005); levels of self-efficacy of the IG increased during intervention (t2: p=.001). Changes in volitional aspects were significant over time (t1-t3), but not specifically for the IG. The intervention was effective at increasing the level of physical activity in patients with mental illness who were initially minimally active. Our results suggest that it could be of great use to place the emphasis of a physical activity-enhancing intervention on its motivational effect since volitional aspects are already taken into sufficient account in standard rehabilitation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Reduced Response to Activated Protein C Is Associated with Increased Risk for Cerebrovascular Disease

    NARCIS (Netherlands)

    Bom, J.G. van der; Bots, M.L.; Haverkate, F.; Slagboom, P.E.; Meijer, P.; Jong, P.T.V.M. de; Hofman, A.; Grobbee, D.E.; Kluft, C.

    1996-01-01

    Background: Resistance to activated protein C (APC), which results from various factors, including a mutation in the gene for coagulant factor V, has been associated with increased risk for venous thrombosis. However, its relation to arterial disease is still not well defined. Objective: To

  15. 75 FR 64348 - BOEMRE Information Collection Activity: 1010-0182, Increased Safety Measures for Energy...

    Science.gov (United States)

    2010-10-19

    ... No. BOEM-2010-0052] BOEMRE Information Collection Activity: 1010-0182, Increased Safety Measures for... the likelihood of blowouts, loss of well control, fires, spillages, physical obstruction to other... subsequent oil spill in the Gulf of Mexico. These events highlight the importance of ensuring safe operations...

  16. Increased Granulocyte Heparanase Activity in Neutrophils from Patients with Lupus Nephritis and Idiopathic Membranous Nephropathy.

    Science.gov (United States)

    Szymczak, Maciej; Kuźniar, Jakub; Kopeć, Wacław; Żabińska, Marcelina; Marchewka, Zofia; Kościelska-Kasprzak, Katarzyna; Klinger, Marian

    2017-02-01

    Heparanase is a β-glucuronidase that cleaves sugar chains of heparan sulfate proteoglycans. It is believed that heparanase may be involved in the pathogenesis of proteinuria. The aim of this study was to assess the significance of heparanase in the pathogenesis of particular glomerulonephritis types. The evaluation of heparanase activity in serum, urine, and granulocytes and superoxide dismutase (SOD) activity in granulocytes of patients with lupus nephritis (n = 17), membranous nephropathy (n = 11), IgA nephropathy (n = 12), focal and segmental glomerulosclerosis (n = 18), mesangiocapillary glomerulonephritis (n = 12) and in 19 healthy volunteers were performed. The heparanase activity in granulocytes of patients with lupus nephritis and membranous nephropathy was higher than heparanase activity in granulocytes in the control group (p = 0.02 in both cases). This is the first observation of this phenomenon. There was no difference between SOD activity in granulocytes of patients with all assessed types of glomerulonephritis and the control group. A positive correlation between heparanase activity in urine and double-strain DNA antibodies (r = 0.51; p = 0.04), and reverse correlations between heparanase in urine and hemolytic activity of the complement (r = -0.57; p = 0.03) in the lupus nephritis group, and between heparanase activity in granulocytes and serum total protein level (r = -0.69; p = 0.02) in membranous nephropathy were observed. Increase in heparanase activity without changes in superoxide dismutase activity in the granulocytes from patients with lupus nephritis and membranous nephropathy was observed. It may be used as one of the markers of these disease activities.

  17. Increased Arf/p53 activity in stem cells, aging and cancer.

    Science.gov (United States)

    Carrasco-Garcia, Estefania; Moreno, Manuel; Moreno-Cugnon, Leire; Matheu, Ander

    2017-04-01

    Arf/p53 pathway protects the cells against DNA damage induced by acute stress. This characteristic is the responsible for its tumor suppressor activity. Moreover, it regulates the chronic type of stress associated with aging. This is the basis of its anti-aging activity. Indeed, increased gene dosage of Arf/p53 displays elongated longevity and delayed aging. At a cellular level, it has been recently shown that increased dosage of Arf/p53 delays age-associated stem cell exhaustion and the subsequent decline in tissue homeostasis and regeneration. However, p53 can also promote aging if constitutively activated. In this context, p53 reduces tissue regeneration, which correlates with premature exhaustion of stem cells. We discuss here the current evidence linking the Arf/p53 pathway to the processes of aging and cancer through stem cell regulation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  18. Plants increase laccase activity in soil with long-term elevated CO2 legacy

    DEFF Research Database (Denmark)

    Partavian, Asrin; Mikkelsen, Teis Nørgaard; Vestergård, Mette

    2015-01-01

    [CO2] stimulate laccase activity. We incubated soil exposed to seven years of elevated or ambient field [CO2] in ambient or elevated [CO2] chambers for six months either with or without plants (Deschampsia flexuosa). Elevated chamber [CO2] increased D. flexuosa production and belowground respiration....... Interestingly, plants also grew larger in soil with an elevated [CO2] legacy. Plants stimulated soil microbial biomass, belowground respiration and laccase activity, and the plant-induced laccase stimulation was particularly apparent in soil exposed to long-term elevated [CO2] in the field, whereas laccase......Actively growing plants can stimulate mineralization of recalcitrant soil organic matter (SOM), and increased atmospheric [CO2] can further enhance such plant-mediated SOM degradation. Laccases are central for recalcitrant SOM decomposition, and we therefore hypothesized that plants and elevated...

  19. Local Factors Influencing The Increase In Development Activity In Selected Cities Of Poland

    Directory of Open Access Journals (Sweden)

    Antczak-Stępniak Agata

    2015-09-01

    Full Text Available Development activity in Poland began to increase in the 1990's as a result of market-oriented reforms, with the process continuing to this day. The beginnings were, however, not easy due to, among others, the absence of many important legal regulations and the lack of commercial financing. The situation changed in the second half of the 1990's, positively affecting residential development activity. The years 2008 - 2009 were particularly relevant in the course of the studied trend as a sharp increase in the number of completed developer-built residential dwelling units was recorded at this time. After this period, a decline in the number of dwelling units completed by developers was recorded, which indicates its strong dependence on changes in the economic environment. Fluctuations in the number of dwelling units completed by developers were also visible before Poland's accession to the European Union. This means that the diversity of development activity is influenced by many factors.

  20. Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Skouby, Sven O; Kluft, Cornelis

    2011-01-01

    Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P=0.001). OC use increased FSAP antigen by 25% and FSAP activity...