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Sample records for human disturbance alters

  1. Increased tolerance to humans among disturbed wildlife

    Science.gov (United States)

    Samia, Diogo S. M.; Nakagawa, Shinichi; Nomura, Fausto; Rangel, Thiago F.; Blumstein, Daniel T.

    2015-01-01

    Human disturbance drives the decline of many species, both directly and indirectly. Nonetheless, some species do particularly well around humans. One mechanism that may explain coexistence is the degree to which a species tolerates human disturbance. Here we provide a comprehensive meta-analysis of birds, mammals and lizards to investigate species tolerance of human disturbance and explore the drivers of this tolerance in birds. We find that, overall, disturbed populations of the three major taxa are more tolerant of human disturbance than less disturbed populations. The best predictors of the direction and magnitude of bird tolerance of human disturbance are the type of disturbed area (urbanized birds are more tolerant than rural or suburban populations) and body mass (large birds are more tolerant than small birds). By identifying specific features associated with tolerance, these results guide evidence-based conservation strategies to predict and manage the impacts of increasing human disturbance on birds. PMID:26568451

  2. Increased tolerance to humans among disturbed wildlife.

    Science.gov (United States)

    Samia, Diogo S M; Nakagawa, Shinichi; Nomura, Fausto; Rangel, Thiago F; Blumstein, Daniel T

    2015-11-16

    Human disturbance drives the decline of many species, both directly and indirectly. Nonetheless, some species do particularly well around humans. One mechanism that may explain coexistence is the degree to which a species tolerates human disturbance. Here we provide a comprehensive meta-analysis of birds, mammals and lizards to investigate species tolerance of human disturbance and explore the drivers of this tolerance in birds. We find that, overall, disturbed populations of the three major taxa are more tolerant of human disturbance than less disturbed populations. The best predictors of the direction and magnitude of bird tolerance of human disturbance are the type of disturbed area (urbanized birds are more tolerant than rural or suburban populations) and body mass (large birds are more tolerant than small birds). By identifying specific features associated with tolerance, these results guide evidence-based conservation strategies to predict and manage the impacts of increasing human disturbance on birds.

  3. Anthropogenic halo disturbances alter landscape and plant richness: a ripple effect.

    Directory of Open Access Journals (Sweden)

    Bingliang Liu

    Full Text Available Although anthropogenic landscape fragmentation is often considered as the primary threat to biodiversity, other factors such as immediate human disturbances may also simultaneously threaten species persistence in various ways. In this paper, we introduce a conceptual framework applied to recreation landscapes (RLs, with an aim to provide insight into the composite influences of landscape alteration accompanying immediate human disturbances on plant richness dynamics. These impacts largely occur at patch-edges. They can not only alter patch-edge structure and environment, but also permeate into surrounding natural matrices/patches affecting species persistence-here we term these "Halo disturbance effects" (HDEs. We categorized species into groups based on seed or pollen dispersal mode (animal- vs. wind-dispersed as they can be associated with species richness dynamics. We evaluated the richness of the two groups and total species in our experimental landscapes by considering the distance from patch-edge, the size of RLs and the intensity of human use over a six-year period. Our results show that animal-dispersed species decreased considerably, whereas wind-dispersed species increased while their richness presented diverse dynamics at different distances from patch-edges. Our findings clearly demonstrate that anthropogenic HDEs produce ripple effects on plant, providing an experimental interpretation for the diverse responses of species to anthropogenic disturbances. This study highlights the importance of incorporating these composite threats into conservation and management strategies.

  4. Anthropogenic halo disturbances alter landscape and plant richness: a ripple effect.

    Science.gov (United States)

    Liu, Bingliang; Su, Jinbao; Chen, Jianwei; Cui, Guofa; Ma, Jianzhang

    2013-01-01

    Although anthropogenic landscape fragmentation is often considered as the primary threat to biodiversity, other factors such as immediate human disturbances may also simultaneously threaten species persistence in various ways. In this paper, we introduce a conceptual framework applied to recreation landscapes (RLs), with an aim to provide insight into the composite influences of landscape alteration accompanying immediate human disturbances on plant richness dynamics. These impacts largely occur at patch-edges. They can not only alter patch-edge structure and environment, but also permeate into surrounding natural matrices/patches affecting species persistence-here we term these "Halo disturbance effects" (HDEs). We categorized species into groups based on seed or pollen dispersal mode (animal- vs. wind-dispersed) as they can be associated with species richness dynamics. We evaluated the richness of the two groups and total species in our experimental landscapes by considering the distance from patch-edge, the size of RLs and the intensity of human use over a six-year period. Our results show that animal-dispersed species decreased considerably, whereas wind-dispersed species increased while their richness presented diverse dynamics at different distances from patch-edges. Our findings clearly demonstrate that anthropogenic HDEs produce ripple effects on plant, providing an experimental interpretation for the diverse responses of species to anthropogenic disturbances. This study highlights the importance of incorporating these composite threats into conservation and management strategies.

  5. Regional boreal biodiversity peaks at intermediate human disturbance.

    Science.gov (United States)

    Mayor, S J; Cahill, J F; He, F; Sólymos, P; Boutin, S

    2012-01-01

    The worldwide biodiversity crisis has intensified the need to better understand how biodiversity and human disturbance are related. The 'intermediate disturbance hypothesis' suggests that disturbance regimes generate predictable non-linear patterns in species richness. Evidence often contradicts intermediate disturbance hypothesis at small scales, and is generally lacking at large regional scales. Here, we present the largest extent study of human impacts on boreal plant biodiversity to date. Disturbance extent ranged from 0 to 100% disturbed in vascular plant communities, varying from intact forest to agricultural fields, forestry cut blocks and oil sands. We show for the first time that across a broad region species richness peaked in communities with intermediate anthropogenic disturbance, as predicted by intermediate disturbance hypothesis, even when accounting for many environmental covariates. Intermediate disturbance hypothesis was consistently supported across trees, shrubs, forbs and grasses, with temporary and perpetual disturbances. However, only native species fit this pattern; exotic species richness increased linearly with disturbance.

  6. [Ecotourism disturbances to non-human primates].

    Science.gov (United States)

    Fan, Peng-Lai; Xiang, Zuo-Fu

    2013-02-01

    In tandem with economic growth and rising living conditions, ecotourism has increasingly gained popularity among the Chinese public. Non-human primates, as charismatic animals and the closest relatives of human beings, have shown a strong affinity in attracting the general public and raising money, and for that reason a variety of monkey parks, valleys, and islands are becoming increasingly popular in China. Though successful in raising a substantial sum of money for the managing agency of a nature reserve, there may be negative impacts on monkey groups used in ecotourism. Here, to establish effective guards for non-human primates involved in ecotourism, we present a review on tourism disturbance and summarize the negative impacts on behavioral patterns, reproduction, and health condition of animals.

  7. Forest legacies, climate change, altered disturbance regimes, invasive species and water

    Science.gov (United States)

    Stohlgren, T.; Jarnevich, C.; Kumar, S.

    2007-01-01

    The factors that must be considered in seeking to predict changes in water availability has been examined. These factors are the following: forest legacies including logging, mining, agriculture, grazing, elimination of large carnivores, human-caused wildfire, and pollution; climate change and stream flow; altered disturbances such as frequency intensity and pattern of wildfires and insect outbreaks as well as flood control; lastly, invasive species like forest pests and pathogens. An integrated approach quantifying the current and past condition trends can be combined with spatial and temporal modeling to develop future change in forest structures and water supply. The key is a combination of geographic information system technologies with climate and land use scenarios, while preventing and minimizing the effects of harmful invasive species.

  8. Altered cortical expression of GABA-related genes in schizophrenia: illness progression vs developmental disturbance.

    Science.gov (United States)

    Hoftman, Gil D; Volk, David W; Bazmi, H Holly; Li, Siyu; Sampson, Allan R; Lewis, David A

    2015-01-01

    Schizophrenia is a neurodevelopmental disorder with altered expression of GABA-related genes in the prefrontal cortex (PFC). However, whether these gene expression abnormalities reflect disturbances in postnatal developmental processes before clinical onset or arise as a consequence of clinical illness remains unclear. Expression levels for 7 GABA-related transcripts (vesicular GABA transporter [vGAT], GABA membrane transporter [GAT1], GABAA receptor subunit α1 [GABRA1] [novel in human and monkey cohorts], glutamic acid decarboxylase 67 [GAD67], parvalbumin, calretinin, and somatostatin [previously reported in human cohort, but not in monkey cohort]) were quantified in the PFC from 42 matched pairs of schizophrenia and comparison subjects and from 49 rhesus monkeys ranging in age from 1 week postnatal to adulthood. Levels of vGAT and GABRA1, but not of GAT1, messenger RNAs (mRNAs) were lower in the PFC of the schizophrenia subjects. As previously reported, levels of GAD67, parvalbumin, and somatostatin, but not of calretinin, mRNAs were also lower in these subjects. Neither illness duration nor age accounted for the levels of the transcripts with altered expression in schizophrenia. In monkey PFC, developmental changes in expression levels of many of these transcripts were in the opposite direction of the changes observed in schizophrenia. For example, mRNA levels for vGAT, GABRA1, GAD67, and parvalbumin all increased with age. Together with published reports, these findings support the interpretation that the altered expression of GABA-related transcripts in schizophrenia reflects a blunting of normal postnatal development changes, but they cannot exclude a decline during the early stages of clinical illness. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Landscape-based assessment of human disturbance for michigan lakes.

    Science.gov (United States)

    Wang, Lizhu; Wehrly, Kevin; Breck, James E; Kraft, Lidia Szabo

    2010-09-01

    Assessment of lake impairment status and identification of threats' type and source is essential for protection of intact, enhancement of modified, and restoration of impaired lakes. For regions in which large numbers of lakes occur, such assessment has usually been done for only small fractions of lakes due to resource and time limitation. This study describes a process for assessing lake impairment status and identifying which human disturbances have the greatest impact on each lake for all lakes that are 2 ha or larger in the state of Michigan using readily available, georeferenced natural and human disturbance databases. In-lake indicators of impairment are available for only a small subset of lakes in Michigan. Using statistical relationships between the in-lake indicators and landscape natural and human-induced measures from the subset lakes, we assessed the likely human impairment condition of lakes for which in-lake indicator data were unavailable using landscape natural and human disturbance measures. Approximately 92% of lakes in Michigan were identified as being least to marginally impacted and about 8% were moderately to heavily impacted by landscape human disturbances. Among lakes that were heavily impacted, more inline lakes (92%) were impacted by human disturbances than disconnected (6%) or headwater lakes (2%). More small lakes were impacted than medium to large lakes. For inline lakes, 90% of the heavily impacted lakes were less than 40 ha, 10% were between 40 and 405 ha, and 1% was greater than 405 ha. For disconnected and headwater lakes, all of the heavily impacted lakes were less than 40 ha. Among the anthropogenic disturbances that contributed the most to lake disturbance index scores, nutrient yields and farm animal density affected the highest number of lakes, agricultural land use affected a moderate number of lakes, and point-source pollution and road measures affected least number of lakes. Our process for assessing lake condition

  10. Sleep disturbance in mild cognitive impairment is associated with alterations in the brain's default mode network.

    Science.gov (United States)

    McKinnon, Andrew C; Lagopoulos, Jim; Terpening, Zoe; Grunstein, Ron; Hickie, Ian B; Batchelor, Jennifer; Lewis, Simon J G; Duffy, Shantel; Shine, James M; Naismith, Sharon L

    2016-06-01

    This study aimed to identify default mode network (DMN) functional connectivity deficits in patients with mild cognitive impairment (MCI) and sleep disturbance, relative to those with MCI and no sleep disturbance. A control group was included to aid in identifying DMN changes specific to MCI. A cross-sectional, single-center study was performed at the Brain and Mind Research Centre in Sydney, Australia. Participants (95 adults over the age of 65: 38 controls and 57 meeting criteria for MCI) underwent resting-state functional MRI along with comprehensive neuropsychological, medical, and psychiatric assessment. Self-report data were collected including sleep quality assessment via the Pittsburgh Sleep Quality Index. A total score of greater than 5 on the Pittsburgh Sleep Quality Index was used to signify the presence of significant sleep disturbance, as per commonly used methodology. Using this criterion, 53% (n = 30) of our MCI group were classified as sleep-disturbed. Whereas the total group of MCI subjects and controls demonstrated no significant differences, sleep-disturbed MCIs demonstrated increased connectivity between temporal and parietal regions, and decreased connectivity between the prefrontal cortex and the temporoparietal junction relative to sleep-disturbed controls. Relative to those MCIs without sleep disturbance, sleep-disturbed MCI participants demonstrated significantly diminished DMN connectivity between temporal and parietal regions, a finding that was particularly pronounced in amnestic MCI. Sleep disturbance in MCI is associated with distinct alterations in DMN functional connectivity in brain regions underpinning salient memory and sleep systems. Future studies may build on these results via experimental manipulation and objective measurement of sleep. (PsycINFO Database Record

  11. Inter-specific variation in avian responses to human disturbance

    Science.gov (United States)

    Daniel T. Blumstein; Esteban Fernandez-Juricic; Patrick A. Zollner; Susan C. Garity

    2005-01-01

    1. Increasing urbanization and recreational activities around and within biodiversity hotspots require an understanding of how to reduce the impacts of human disturbance on more than a single species; however, we lack a general framework to study multiple species. One approach is to expand on knowledge about the theory of anti-predator behaviour to understand and...

  12. Human reproductive system disturbances and pesticide exposure in Brazil

    OpenAIRE

    Sergio Koifman; Rosalina Jorge Koifman; Armando Meyer

    2002-01-01

    The observation of reproductive disturbances in humans and in the wildlife has been reported in the last decade in different countries. Exposure to different chemicals possibly acting in the endocrine system or endocrine disruptors, including pesticides, has been a hypothesis raised to explain the observed changes. This paper aimed to present results of an epidemiological ecologic study carried out to explore population data on pesticides exposure in selected Brazilian states in the eighties ...

  13. Disturbance Distance: Using a process based ecosystem model to estimate and map potential thresholds in disturbance rates that would give rise to fundamentally altered ecosystems

    Science.gov (United States)

    Dolan, K. A.; Hurtt, G. C.; Fisk, J.; Flanagan, S.; LePage, Y.; Sahajpal, R.

    2014-12-01

    Disturbance plays a critical role in shaping the structure and function of forested ecosystems as well as the ecosystem services they provide, including but not limited to: carbon storage, biodiversity habitat, water quality and flow, and land atmosphere exchanges of energy and water. As recent studies highlight novel disturbance regimes resulting from pollution, invasive pests and climate change, there is a need to include these alterations in predictions of future forest function and structure. The Ecosystem Demography (ED) model is a mechanistic model of forest ecosystem dynamics in which individual-based forest dynamics can be efficiently implemented over regional to global scales due to advanced scaling methods. We utilize ED to characterize the sensitivity of potential vegetation structure and function to changes in rates of density independent mortality. Disturbance rate within ED can either be altered directly or through the development of sub-models. Disturbance sub-models in ED currently include fire, land use and hurricanes. We use a tiered approach to understand the sensitivity of North American ecosystems to changes in background density independent mortality. Our first analyses were conducted at half-degree spatial resolution with a constant rate of disturbance in space and time, which was altered between runs. Annual climate was held constant at the site level and the land use and fire sub-models were turned off. Results showed an ~ 30% increase in non-forest area across the US when disturbance rates were changed from 0.6% a year to 1.2% a year and a more than 3.5 fold increase in non-forest area when disturbance rates doubled again from 1.2% to 2.4%. Continued runs altered natural background disturbance rates with the existing fire and hurricane sub models turned on as well as historic and future land use. By quantify differences between model outputs that characterize ecosystem structure and function related to the carbon cycle across the US, we

  14. Sandhill crane roost selection, human disturbance, and forage resources

    Science.gov (United States)

    Pearse, Aaron T.; Krapu, Gary; Brandt, David

    2017-01-01

    Sites used for roosting represent a key habitat requirement for many species of birds because availability and quality of roost sites can influence individual fitness. Birds select roost sites based on numerous factors, requirements, and motivations, and selection of roosts can be dynamic in time and space because of various ecological and environmental influences. For sandhill cranes (Antigone canadensis) at their main spring-staging area along the Platte River in south-central Nebraska, USA, past investigations of roosting cranes focused on physical channel characteristics related to perceived security as motivating roost distribution. We used 6,310 roost sites selected by 313 sandhill cranes over 5 spring migration seasons (2003–2007) to quantify resource selection functions of roost sites on the central Platte River using a discrete choice analysis. Sandhill cranes generally showed stronger selection for wider channels with shorter bank vegetation situated farther from potential human disturbance features such as roads, bridges, and dwellings. Furthermore, selection for roost sites with preferable physical characteristics (wide channels with short bank vegetation) was more resilient to nearby disturbance features than more narrow channels with taller bank vegetation. The amount of cornfields surrounding sandhill crane roost sites positively influenced relative probability of use but only for more narrow channels resource features that sandhill cranes selected at river channels along the Platte River, and after incorporating spatial variation due to human disturbance, our understanding of roost site selection was more robust, providing insights on how disturbance may interact with physical habitat features. Managers can use information on roost-site selection when developing plans to increase probability of crane use at existing roost sites and to identify new areas for potential use if existing sites become limited.

  15. Luminescence of thermally altered human skeletal remains

    NARCIS (Netherlands)

    Krap, Tristan; Nota, Kevin; Wilk, Leah; van de Goot, Frank; Ruijter, Jan; Duijst, Wilma; Oostra, Roelof Jan

    2017-01-01

    Literature on luminescent properties of thermally altered human remains is scarce and contradictory. Therefore, the luminescence of heated bone was systemically reinvestigated. A heating experiment was conducted on fresh human bone, in two different media, and cremated human remains were recovered

  16. Effects of geliogeophysical disturbances in haemorheological parameters of human

    Science.gov (United States)

    Ionova, V.; Sergeenko, N.; Sazanova, E.

    The changes of the rheological characteristics of blood at healthy people and patients with cerebrum-vascular pathology during 23 geomagnetic disturbances were studied. The analysis of dynamics of haemorheological parameters of both human groups has shown that the most of parameters are beginning statistically authentically to fall outside the normal limits already prior the beginning of the magnetic disturbance, others - per day of a beginning of disturbance. This fact specifies at an increase of variability for functional activity of blood cell in conditions of geomagnetic disturbance and allows to assume presence of direct influences of an environmental physical processes at the blood cell. The deterioration of deformation properties of erythrocytes is observed in the blood of people. The analysis of the data has resulted in occurrence of a hypothesis about appearance of instability at thrombosis-vascular part of haemostasis under influence of variation of electromagnetic field in during of magnetospheric disturbances. Such effect can be caused as direct and indirect action of an electrîmagnetic field of the Earth on the cells of blood. Haemoglobin of erythrocytes includes atoms of iron, having a deflection of the magnetic moment. In the cells, which had their erythrocytes membrane under influence of an electrîmagnetic field, had diminution of electrical mobility, that can influence the dynamics of physiological process of aggregation --disaggregation of erythrocytes in a stream of blood. Another channel of influence of geomagnetic disturbances on rheological property of blood can be connected with the action of electrîmagnetic fields through synchronization of rhythms of electromagnetic oscillations of cells of central nervous system. From the entire spectrum of an electrîmagnetic field apparent on the surface of the Earth, biologically effective factor is in a range of ultralow frequencies from 0,0001 up to 100 Ãö. The biorhythms of the brain, such as an

  17. Alterations in geochemical associations in artificially disturbed deep-sea sediments

    Digital Repository Service at National Institute of Oceanography (India)

    Nath, B.N.; Parthiban, G.; Banaulikar, S.; Sarkar, S.

    'benthic disturber' were studied for metal variation in three phases: (1) before the disturbance, (2) immediately after the disturbance, and (3) during monitoring of restoration after approx. 44 months, from the same locations. Minor variations in metal...

  18. Human reproductive system disturbances and pesticide exposure in Brazil

    Directory of Open Access Journals (Sweden)

    Koifman Sergio

    2002-01-01

    Full Text Available The observation of reproductive disturbances in humans and in the wildlife has been reported in the last decade in different countries. Exposure to different chemicals possibly acting in the endocrine system or endocrine disruptors, including pesticides, has been a hypothesis raised to explain the observed changes. This paper aimed to present results of an epidemiological ecologic study carried out to explore population data on pesticides exposure in selected Brazilian states in the eighties and human reproductive outcomes in the nineties. Pearson correlation coefficients were ascertained between available data pesticides sales in eleven states in Brazil in 1985 and selected further reproductive outcomes or their surrogates. Moderate to high correlations were observed to infertility, testis, breast, prostate and ovarian cancer mortality. Despite the restrains of ecologic studies to establish cause-effect relationships, the observed results are in agreement with evidence supporting a possible association between pesticides exposure and the analyzed reproductive outcomes.

  19. Luminescence of thermally altered human skeletal remains.

    Science.gov (United States)

    Krap, Tristan; Nota, Kevin; Wilk, Leah S; van de Goot, Franklin R W; Ruijter, Jan M; Duijst, Wilma; Oostra, Roelof-Jan

    2017-07-01

    Literature on luminescent properties of thermally altered human remains is scarce and contradictory. Therefore, the luminescence of heated bone was systemically reinvestigated. A heating experiment was conducted on fresh human bone, in two different media, and cremated human remains were recovered from a modern crematory. Luminescence was excited with light sources within the range of 350 to 560 nm. The excitation light was filtered out by using different long pass filters, and the luminescence was analysed by means of a scoring method. The results show that temperature, duration and surrounding medium determine the observed emission intensity and bandwidth. It is concluded that the luminescent characteristic of bone can be useful for identifying thermally altered human remains in a difficult context as well as yield information on the perimortem and postmortem events.

  20. Large-scale natural disturbance alters genetic population structure of the sailfin molly, Poecilia latipinna.

    Science.gov (United States)

    Apodaca, Joseph J; Trexler, Joel C; Jue, Nathaniel K; Schrader, Matthew; Travis, Joseph

    2013-02-01

    Many inferences about contemporary rates of gene flow are based on the assumption that the observed genetic structure among populations is stable. Recent studies have uncovered several cases in which this assumption is tenuous. Most of those studies have focused on the effects that regular environmental fluctuations can have on genetic structure and gene flow patterns. Occasional catastrophic disturbances could also alter either the distribution of habitat or the spatial distribution of organisms in a way that affects population structure. However, evidence of such effects is sparse in the literature because it is difficult to obtain. Hurricanes, in particular, have the potential to exert dramatic effects on population structure of organisms found on islands or coral reefs or in near shore and coastal habitats. Here we draw on a historic genetic data set and new data to suggest that the genetic structure of sailfin molly (Poecilia latipinna) populations in north Florida was altered dramatically by an unusually large and uncommon type of storm surge associated with Hurricane Dennis in 2005. We compare the spatial pattern of genetic variation in these populations after Hurricane Dennis to the patterns described in an earlier study in this same area. We use comparable genetic data from another region of Florida, collected in the same two periods, to estimate the amount of change expected from typical temporal variation in population structure. The comparative natural history of sailfin mollies in these two regions indicates that the change in population structure produced by the storm surge is not the result of many local extinctions with recolonization from a few refugia but emerged from a pattern of mixing and redistribution.

  1. A Network-Centric Formalism for Disturbance Rejection Design and Human Swarm Interaction

    Science.gov (United States)

    2015-07-06

    AFRL-AFOSR-VA-TR-2016-0007 Formalism for Disturbance Rejection Design and Human- swarm Interaction Mehran Mesbahi UNIVERSITY OF WASHINGTON Final...SUBTITLE A Network-centric Formalism for Disturbance Rejection Design and Human Swarm Interaction 5a. CONTRACT NUMBER FA9550-12-1-0203 5b. GRANT NUMBER...proposed research is to examine fundamental structural bounds on the disturbance rejection and human- swarm interaction properties of a network of

  2. TFIIH subunit alterations causing xeroderma pigmentosum and trichothiodystrophy specifically disturb several steps during transcription.

    Science.gov (United States)

    Singh, Amita; Compe, Emanuel; Le May, Nicolas; Egly, Jean-Marc

    2015-02-01

    Mutations in genes encoding the ERCC3 (XPB), ERCC2 (XPD), and GTF2H5 (p8 or TTD-A) subunits of the transcription and DNA-repair factor TFIIH lead to three autosomal-recessive disorders: xeroderma pigmentosum (XP), XP associated with Cockayne syndrome (XP/CS), and trichothiodystrophy (TTD). Although these diseases were originally associated with defects in DNA repair, transcription deficiencies might be also implicated. By using retinoic acid receptor beta isoform 2 (RARB2) as a model in several cells bearing mutations in genes encoding TFIIH subunits, we observed that (1) the recruitment of the TFIIH complex was altered at the activated RARB2 promoter, (2) TFIIH participated in the recruitment of nucleotide excision repair (NER) factors during transcription in a manner different from that observed during NER, and (3) the different TFIIH variants disturbed transcription by having distinct consequences on post-translational modifications of histones, DNA-break induction, DNA demethylation, and gene-loop formation. The transition from heterochromatin to euchromatin was disrupted depending on the variant, illustrating the fact that TFIIH, by contributing to NER factor recruitment, orchestrates chromatin remodeling. The subtle transcriptional differences found between various TFIIH variants thus participate in the phenotypic variability observed among XP, XP/CS, and TTD individuals.

  3. Meal time shift disturbs circadian rhythmicity along with metabolic and behavioral alterations in mice.

    Science.gov (United States)

    Yoon, Ji-Ae; Han, Dong-Hee; Noh, Jong-Yun; Kim, Mi-Hee; Son, Gi Hoon; Kim, Kyungjin; Kim, Chang-Ju; Pak, Youngmi Kim; Cho, Sehyung

    2012-01-01

    In modern society, growing numbers of people are engaged in various forms of shift works or trans-meridian travels. Such circadian misalignment is known to disturb endogenous diurnal rhythms, which may lead to harmful physiological consequences including metabolic syndrome, obesity, cancer, cardiovascular disorders, and gastric disorders as well as other physical and mental disorders. However, the precise mechanism(s) underlying these changes are yet unclear. The present work, therefore examined the effects of 6 h advance or delay of usual meal time on diurnal rhythmicities in home cage activity (HCA), body temperature (BT), blood metabolic markers, glucose homeostasis, and expression of genes that are involved in cholesterol homeostasis by feeding young adult male mice in a time-restrictive manner. Delay of meal time caused locomotive hyperactivity in a significant portion (42%) of subjects, while 6 h advance caused a torpor-like symptom during the late scotophase. Accordingly, daily rhythms of blood glucose and triglyceride were differentially affected by time-restrictive feeding regimen with concurrent metabolic alterations. Along with these physiological changes, time-restrictive feeding also influenced the circadian expression patterns of low density lipoprotein receptor (LDLR) as well as most LDLR regulatory factors. Strikingly, chronic advance of meal time induced insulin resistance, while chronic delay significantly elevated blood glucose levels. Taken together, our findings indicate that persistent shifts in usual meal time impact the diurnal rhythms of carbohydrate and lipid metabolisms in addition to HCA and BT, thereby posing critical implications for the health and diseases of shift workers.

  4. Disturbances of electrodynamic activity affect abortion in human

    Science.gov (United States)

    Jandová, A.; Nedbalová, M.; Kobilková, J.; Čoček, A.; Dohnalová, A.; Cifra, M.; Pokorný, J.

    2011-12-01

    Biochemical research of biological systems is highly developed, and it has disclosed a spectrum of chemical reactions, genetic processes, and the pathological development of various diseases. The fundamental hypothesis of physical processes in biological systems, in particular of coherent electrically polar vibrations and electromagnetic activity, was formulated by H. Fröhlich he assumed connection of cancer process with degradation of coherent electromagnetic activity. But the questions of cellular structures capable of the coherent electrical polar oscillation, mechanisms of energy supply, and the specific role of the endogenous electromagnetic fields in transport, organisation, interactions, and information transfer remained open. The nature of physical disturbances caused by some diseases (including the recurrent abortion in humans and the cancer) was unknown. We have studied the reasons of recurrent abortions in humans by means of the cell mediated immunity (using immunologic active RNA prepared from blood of inbred laboratory mice strain C3H/H2K, infected with the lactate dehydrogenase elevating virus-LD V) and the cytogenetic examination from karyotype pictures. The recurrent abortion group contained women with dg. spontaneous abortion (n = 24) and the control group was composed of 30 healthy pregnant women. Our hypothesis was related to quality of endometrium in relation to nidation of the blastocyst. The energetic insufficiency (ATP) inhibits normal development of fetus and placenta. We hope that these ideas might have impact on further research, which could provide background for effective interdisciplinary cooperation of malignant and non-malignant diseases.

  5. Morphofunctional disturbances of human sperm after incubation with organophosphorate pesticides.

    Science.gov (United States)

    Contreras, H R; Badilla, J; Bustos-Obregón, E

    1999-08-01

    The organophosphorate pesticides are highly toxic for insects and mammals, but their effects in the male reproductive tract are scarcely known. Many alterations induced by organophosphorate pesticides have been described, such as: cytogenetic alterations in germinal cells, oligozoospermia and teratozoospermia in the mouse. Parathion, the pesticide mostly utilized in Chilean agriculture, is rapidly metabolized to paraoxon, the active metabolite, in mammalian organisms. The purpose of this study is to evaluate the effect of Parathion and paraoxon on different morphological and functional parameters of the sperm. Human spermatozoa were incubated with Parathion and paraoxon at different concentrations (0.05, 0.1, 0.2, 0.4 and 0.8 mM). Vitality (tripan blue and eosin tests), acrosome reaction (triple stain test), plasma membrane integrity (HOS-test), and chromatin stability (sodium thioglycolate test) were determined. The observations were done by optical microscopy at 1000x of magnification and three hundred sperms were evaluated for each treatment. The results indicated that Parathion and paraoxon increase the percent of sperm with acrosome reaction and also increase the percentage of sperm with chromatin decondensation in a dose-dependent manner. The vitality and plasma membrane integrity decrease significantly in a dose-dependent manner. The results suggest a direct action of Parathion and paraoxon on the different parameters studied. The morphofunctionality of sperm is altered significatively, suggesting that Parathion and paraoxon, thanks to their alkylating and electrophylic properties, could act on DNA and proteins respectively, to elicit these changes.

  6. Meal time shift disturbs circadian rhythmicity along with metabolic and behavioral alterations in mice.

    Directory of Open Access Journals (Sweden)

    Ji-Ae Yoon

    Full Text Available In modern society, growing numbers of people are engaged in various forms of shift works or trans-meridian travels. Such circadian misalignment is known to disturb endogenous diurnal rhythms, which may lead to harmful physiological consequences including metabolic syndrome, obesity, cancer, cardiovascular disorders, and gastric disorders as well as other physical and mental disorders. However, the precise mechanism(s underlying these changes are yet unclear. The present work, therefore examined the effects of 6 h advance or delay of usual meal time on diurnal rhythmicities in home cage activity (HCA, body temperature (BT, blood metabolic markers, glucose homeostasis, and expression of genes that are involved in cholesterol homeostasis by feeding young adult male mice in a time-restrictive manner. Delay of meal time caused locomotive hyperactivity in a significant portion (42% of subjects, while 6 h advance caused a torpor-like symptom during the late scotophase. Accordingly, daily rhythms of blood glucose and triglyceride were differentially affected by time-restrictive feeding regimen with concurrent metabolic alterations. Along with these physiological changes, time-restrictive feeding also influenced the circadian expression patterns of low density lipoprotein receptor (LDLR as well as most LDLR regulatory factors. Strikingly, chronic advance of meal time induced insulin resistance, while chronic delay significantly elevated blood glucose levels. Taken together, our findings indicate that persistent shifts in usual meal time impact the diurnal rhythms of carbohydrate and lipid metabolisms in addition to HCA and BT, thereby posing critical implications for the health and diseases of shift workers.

  7. Historical landscape elements in preserving steppic species - vegetation responses on micro-topography and human disturbances

    Science.gov (United States)

    Deák, Balázs; Valkó, Orsolya; Török, Péter; Tóthmérész, Béla

    2017-04-01

    Land use changes of past centuries resulted in a considerable loss and isolation of grassland habitats worldwide which also led to a serious loss in ecosystem functions. In intensively used agricultural landscapes remnants of natural flora persisted only in small habitat islands embedded in a hostile matrix, which are inadequate for arable farming or construction. In the steppe zone of Eurasia burial mounds, so-called kurgans, have a great potential to preserve the natural flora and habitats and act as local biodiversity hotspots. Their special micro-topography and historical origin makes kurgans characteristic landscape elements of the steppe region. These features also result in a specific soil development and micro-climate, which makes kurgans especially adequate habitats for several steppe specialist plant species. Furthermore, they are proper objects for studying the effects of present and past human disturbances on the vegetation of semi-natural habitats. Exploration of the main factors driving biodiversity in isolated habitat fragments is crucial for understanding the ecological processes shaping their vegetation and for designing effective strategies for their protection. We surveyed the vegetation of 44 isolated kurgans in East-Hungary and studied the effects of habitat area, slope, recent disturbance, past destruction and the level of woody encroachment on the species richness and cover of grassland specialist and weedy species. We used model selection techniques and linear models for testing relevant factors affecting specialist species in grassland fragments. We found that the biodiversity conservation potential of kurgans is supported by their steep slopes, which provide adequate habitat conditions and micro-climate for steppic specialist plant species. By harbouring several grassland specialist species, kurgans have a great potential for preserving the natural species pool of even considerably altered agricultural landscapes, and can mitigate the

  8. Diversity loss with persistent human disturbance increases vulnerability to ecosystem collapse.

    Science.gov (United States)

    MacDougall, A S; McCann, K S; Gellner, G; Turkington, R

    2013-02-07

    Long-term and persistent human disturbances have simultaneously altered the stability and diversity of ecological systems, with disturbances directly reducing functional attributes such as invasion resistance, while eliminating the buffering effects of high species diversity. Theory predicts that this combination of environmental change and diversity loss increases the risk of abrupt and potentially irreversible ecosystem collapse, but long-term empirical evidence from natural systems is lacking. Here we demonstrate this relationship in a degraded but species-rich pyrogenic grassland in which the combined effects of fire suppression, invasion and trophic collapse have created a species-poor grassland that is highly productive, resilient to yearly climatic fluctuations, and resistant to invasion, but vulnerable to rapid collapse after the re-introduction of fire. We initially show how human disturbance has created a negative relationship between diversity and function, contrary to theoretical predictions. Fire prevention since the mid-nineteenth century is associated with the loss of plant species but it has stabilized high-yield annual production and invasion resistance, comparable to a managed high-yield low-diversity agricultural system. In managing for fire suppression, however, a hidden vulnerability to sudden environmental change emerges that is explained by the elimination of the buffering effects of high species diversity. With the re-introduction of fire, grasslands only persist in areas with remnant concentrations of native species, in which a range of rare and mostly functionally redundant plants proliferate after burning and prevent extensive invasion including a rapid conversion towards woodland. This research shows how biodiversity can be crucial for ecosystem stability despite appearing functionally insignificant beforehand, a relationship probably applicable to many ecosystems given the globally prevalent combination of intensive long-term land

  9. Soil disturbance alters plant community composition and decreases mycorrhizal carbon allocation in a sandy grassland.

    Science.gov (United States)

    Schnoor, Tim Krone; Mårtensson, Linda-Maria; Olsson, Pål Axel

    2011-11-01

    We have studied how disturbance by ploughing and rotavation affects the carbon (C) flow to arbuscular mycorrhizal (AM) fungi in a dry, semi-natural grassland. AM fungal biomass was estimated using the indicator neutral lipid fatty acid (NLFA) 16:1ω5, and saprotrophic fungal biomass using NLFA 18:2ω6,9. We labeled vegetation plots with (13)CO(2) and studied the C flow to the signature fatty acids as well as uptake and allocation in plants. We found that AM fungal biomass in roots and soil decreased with disturbance, while saprotrophic fungal biomass in soil was not influenced by disturbance. Rotavation decreased the (13)C enrichment in NLFA 16:1ω5 in soil, but (13)C enrichment in the AM fungal indicator NLFA 16:1ω5 in roots or soil was not influenced by any other disturbance. In roots, (13)C enrichment was consistently higher in NLFA 16:1ω5 than in crude root material. Grasses (mainly Festuca brevipila) decreased as a result of disturbance, while non-mycorrhizal annual forbs increased. This decreases the potential for mycorrhizal C sequestration and may have been the main reason for the reduced mycorrhizal C allocation found in disturbed plots. Disturbance decreased the soil ammonium content but did not change the pH, nitrate or phosphate availability. The overall effect of disturbance on C allocation was that more of the C in AM fungal mycelium was directed to the external phase. Furthermore, the functional identity of the plants seemed to play a minor role in the C cycle as no differences were seen between different groups, although annuals contained less AM fungi than the other groups.

  10. Are old Mediterranean grasslands resilient to human disturbances?

    Science.gov (United States)

    Coiffait-Gombault, Clémentine; Buisson, Elise; Dutoit, Thierry

    2012-08-01

    Many dry herbaceous ecosystems suffer damage and are characterized by low resilience after disturbance. Among these forms of disturbance, soil excavation due to the construction of underground pipelines affects vegetation at plant community and landscape scales. Synchronic studies are the best approach for more rapid study of plant succession on ecosystems with low resilience. In order to better understand plant succession in a Mediterranean dry grassland, we compared the effect of a recent disturbance caused by the digging of a pipeline in 2006 with that of a pipeline created in 1972 in the same area. Surveys of floristic composition and richness were carried out along both pipelines in order to understand the succession after this single disturbance, one that does not drastically change soil chemical properties unlike former agricultural practices. Nevertheless, this type of disturbance still changes the floristic composition in the long term (>30 years). The first stage begins just after disturbance with the occurrence of many weed species. Another level between the first and the mature stage was characterized in our study, 30 years after the disturbance, by an assemblage of annual and perennial species but still lacking species typical of the reference steppe. The reference steppe is described as the mature level of the succession with an assemblage of typical grasses, forbs and a few small chamaephytes and, in particular, by the presence of Brachypodium retusum. This community corresponds to a very old Mediterranean grassland that has evolved under the Mediterranean climate and traditional sheep grazing management systems since the Neolithic Age. This study confirms the low resilience of this steppe community and shows the importance of pursuing research on this steppe and in particular on the biotic and abiotic processes involved in community assembly.

  11. Alterations of 5-Hydroxymethylcytosine in Human Cancers

    Directory of Open Access Journals (Sweden)

    Ali Yesilkanal

    2013-06-01

    Full Text Available Prior to 2009, 5-methylcytosine (5-mC was thought to be the only biologically significant cytosine modification in mammalian DNA. With the discovery of the TET enzymes, which convert 5-methylcytosine (5-mC to 5-hydroxymethylcytosine (5-hmC, however, intense interest has emerged in determining the biological function of 5-hmC. Here, we review the techniques used to study 5-hmC and evidence that alterations to 5-hmC physiology play a functional role in the molecular pathogenesis of human cancers.

  12. Human disturbance causes the formation of a hybrid swarm between two naturally sympatric fish species.

    Science.gov (United States)

    Hasselman, Daniel J; Argo, Emily E; McBride, Meghan C; Bentzen, Paul; Schultz, Thomas F; Perez-Umphrey, Anna A; Palkovacs, Eric P

    2014-03-01

    Most evidence for hybrid swarm formation stemming from anthropogenic habitat disturbance comes from the breakdown of reproductive isolation between incipient species, or introgression between allopatric species following secondary contact. Human impacts on hybridization between divergent species that naturally occur in sympatry have received considerably less attention. Theory predicts that reinforcement should act to preserve reproductive isolation under such circumstances, potentially making reproductive barriers resistant to human habitat alteration. Using 15 microsatellites, we examined hybridization between sympatric populations of alewife (Alosa pseudoharengus) and blueback herring (A. aestivalis) to test whether the frequency of hybridization and pattern of introgression have been impacted by the construction of a dam that isolated formerly anadromous populations of both species in a landlocked freshwater reservoir. The frequency of hybridization and pattern of introgression differed markedly between anadromous and landlocked populations. The rangewide frequency of hybridization among anadromous populations was generally 0-8%, whereas all landlocked individuals were hybrids. Although neutral introgression was observed among anadromous hybrids, directional introgression leading to increased prevalence of alewife genotypes was detected among landlocked hybrids. We demonstrate that habitat alteration can lead to hybrid swarm formation between divergent species that naturally occur sympatrically, and provide empirical evidence that reinforcement does not always sustain reproductive isolation under such circumstances.

  13. Altered chromosome 6 in immortal human fibroblasts.

    Science.gov (United States)

    Hubbard-Smith, K; Patsalis, P; Pardinas, J R; Jha, K K; Henderson, A S; Ozer, H L

    1992-05-01

    Human diploid fibroblasts have a limited life span in vitro, and spontaneous immortalization is an extremely rare event. We have used transformation of human diploid fibroblasts by an origin-defective simian virus 40 genome to develop series of genetically matched immortal cell lines to analyze immortalization. Comparison of a preimmortal transformant (SVtsA/HF-A) with its uncloned and cloned immortalized derivatives (AR5 and HAL) has failed to reveal any major alteration involving the simian virus 40 genome. Karyotypic analysis, however, demonstrated that all of the immortal cell lines in this series have alterations of chromosome 6 involving loss of the portion distal to 6q21. The karyotypic analysis was corroborated by DNA analyses. Southern analysis demonstrated that only one copy of three proto-oncogene loci (ros1, c-myb, and mas1) on 6q was retained in immortal cells. Polymerase chain reaction analysis of the microsatellite polymorphism at 6q22 (D6S87) showed loss of heterozygosity. In addition, elevated expression of c-myb (6q22-23) was observed. We hypothesize that the region at and/or distal to 6q21 plays a role in immortalization, consistent with the presence of a growth suppressor gene.

  14. Altered chromosome 6 in immortal human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Hubbard-Smith, K.; Pardinas, J.R.; Jha, K.K.; Ozer, H.L. (New Jersey Medical School, Newark, NJ (United States)); Patsalis, P.; Henderson, A.S. (City Univ. of New York, NY (United States))

    1992-05-01

    Human diploid fibroblasts have a limited life span in vitro, and spontaneous immortalization is an extremely rare event. We have used transformation of human diploid fibroblasts by an origin-defective simian virus 40 genome to develop series of genetically matched immortal cell lines to analyze immortalization. Comparison of a preimmortal transformant (SVtsA/HF-A) with its uncloned and cloned immortalized derivatives (AR5 and HAL) has failed to reveal any major alteration involving the simian virus 40 genome. Karyotypic analysis, however, demonstrated that all of the immortal cell lines in this series have alterations of chromosome 6 involving loss of the portion distal to 6q21. The karyotypic analysis was corroborated by DNA analyses. Southern analysis demonstrated that only one copy of three proto-oncogene loci (ros1, c-myb, and mas1) on 6q was retained in immortal cells. Polymerase chain reaction analysis of the microsatellite polymorphism at 6q22 (D6S87) showed loss of heterozygosity. In addition, elevated expression of c-myb (6q22-23) was observed. We hypothesize that the region at and/or distal to 6q21 plays a role in immortalization, consistent with the presence of a growth suppressor gene. 66 refs., 6 figs., 2 tabs.

  15. The history of human disturbance in forest ecosystems of southern Indiana

    Science.gov (United States)

    Michael A. Jenkins

    2013-01-01

    The forests of southern Indiana have been shaped and defined by anthropogenic disturbance. Native Americans influenced composition and structure through land clearing and burning, but the scale and rate of human disturbance intensified with European settlement. Sustained settlement led to the loss of forest land to agriculture and livestock grazing. Forests were also...

  16. Evaluating human-disturbed habitats for recovery planning of endangered plants.

    Science.gov (United States)

    Robinson, Julie; Hermanutz, Luise

    2015-03-01

    The recovery potential of endangered species is limited by the high prevalence of human-modified habitats, while effective in situ conservation strategies to identify and restore disturbed habitat within species ranges are lacking. Our goal was to determine the impact of human disturbance on the endangered endemic Barrens willow (Salix jejuna) to provide science-based protocols for future restoration of disturbed habitats; a key component of conservation and recovery plans for many rare plant species. Our study examined differences in substrate (e.g., % total plant cover, % species cover, substrate type) and vegetation in naturally- (via frost activity) vs human-disturbed limestone barrens (Newfoundland, Canada), across the entire species range of the endangered Barrens willow. There were distinct differences in substrate conditions and vegetation community structure between naturally- and human-disturbed limestone barrens habitat throughout the narrow range of this endemic willow. Human-disturbed sites are more homogeneous and differ significantly from the naturally-disturbed sites having a much coarser substrate (30% more gravel) with less fine grained sands, less exposed bedrock, decreased soil moisture, increased nitrogen content, and reduced phosphorus content. Substrate differences can inhibit return to the natural freeze-thaw disturbance regime of the limestone barrens, negatively affecting long-term persistence of this, and other rare plants. The structure of associated vegetation (specifically woody species presence) negatively affected willow abundance but was not linked to disturbance type. Human-disturbed sites are potential candidates for endangered plant recovery habitat if natural ecosystem processes, vegetation community structure, and habitat heterogeneity are restored, thereby supporting the establishment of long term viable populations.

  17. Ibuprofen results in alterations of human fetal testis development

    Science.gov (United States)

    Ben Maamar, Millissia; Lesné, Laurianne; Hennig, Kristin; Desdoits-Lethimonier, Christèle; Kilcoyne, Karen R.; Coiffec, Isabelle; Rolland, Antoine D.; Chevrier, Cécile; Kristensen, David M.; Lavoué, Vincent; Antignac, Jean-Philippe; Le Bizec, Bruno; Dejucq-Rainsford, Nathalie; Mitchell, Rod T.; Mazaud-Guittot, Séverine; Jégou, Bernard

    2017-01-01

    Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7–17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8–9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10–12 GW, or in second trimester xenografted testes (14–17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow ‘early window’ of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology. PMID:28281692

  18. Phytolith assemblages along a gradient of ancient human disturbance in western Amazonia

    Directory of Open Access Journals (Sweden)

    Crystal eMcmichael

    2015-12-01

    Full Text Available The ecological status of prehistoric Amazonian forests remains widely debated. The concept of ancient Amazonia as a pristine wilderness is largely discredited, but the alternative hypothesis of extensive anthropogenic landscape remains untested in many regions. We assessed the degree of ancient human impacts across western Amazonia based on archaeological and paleoecological data using methodologies that would allow inter-regional comparisons. We also aimed to establish baselines for estimating the legacies of ancient disturbances on modern vegetation. We analyzed charcoal and phytolith assemblages from soil samples from an archaeological site, sites in close proximity to archaeological sites, sites from riverine and interfluvial forests, and a biological research station believed to contain some of the least disturbed forests within Amazonia. We then quantitatively compared phytolith assemblages within and between the surveyed regions. Palm enrichment was evident at the archaeological site, and the biological station survey contained little to no evidence of ancient human activity. The other sites exhibited a gradient of ancient disturbance across the landscape. The phytolith assemblages showed statistically significant between-region variations that indicated our metrics were sufficiently sensitive to detecting ancient disturbance. Our data highlight the spatial heterogeneity of ancient human disturbances in Amazonian forests. The quantification of these disturbances provides empirical data and a more concrete link between the composition of the modern forest and ancient disturbance regimes. Accounting for ancient disturbances will allow a deeper understanding of the landscape heterogeneity observed in the modern forests.

  19. Catchment controls and human disturbances on the geomorphology of small Mediterranean estuarine systems

    Science.gov (United States)

    Estrany, Joan; Grimalt, Miquel

    2014-10-01

    terraces and transverse walls are involved in the generation of catastrophic flood events. Additionally, the lagoons were altered considerably by human intervention for flood control and to allow for an increased amount of human activities within the surrounding areas, although the high recurrence of catastrophic flood events causes a persistent difficulty in the human battle to dominate these ecosystems. Therefore, the area occupied by lagoons increased between 1956 and the present time from 31,981 m2 to 63,802 m2 because of the high recurrence of catastrophic flood events. Furthermore, tourism demand and a social conservation consciousness have promoted restoration and preservation since the 1990s. This study has improved the geomorphological knowledge of small Mediterranean estuaries affected by human disturbances in the high-energy environment found in Mallorca.

  20. Foraging Behavior and the Effect of Human Disturbance on the Piping Plover (Charadrius melodus)

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This study discusses the status of the species, habitat requirements and limiting factors with emphasis upon effects of human disturbances on nesting birds. In this...

  1. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds

    OpenAIRE

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J.

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breedin...

  2. [Dynamic changes of soil ecological factors in Ziwuling secondary forest area under human disturbance].

    Science.gov (United States)

    Zhou, Zhengchao; Shangguan, Zhouping

    2005-09-01

    As a widespread natural phenomenon, disturbance is considered as a discrete event occurred in natural ecosystems at various spatial and temporal scales. The occurrence of disturbance directly affects the structure, function and dynamics of ecosystems. Forest logging and forestland assart, the common human disturbances in forest area, have caused the dynamic changes of forest soil ecological factors in a relatively consistent environment. A study on the dynamics of soil bulk density, soil organic matter, soil microbes and other soil ecological factors under different human disturbance (logging and assart, logging but without assart, control) were conducted in the Ziwuling secondary forest area. The results indicated that human disturbance had a deep impact on the soil ecological factors, with soil physical and chemical properties become bad, soil organic matter decreased from 2.2% to 0.8%, and soil stable aggregates dropped more than 30%. The quantity of soil microbes decreased sharply with enhanced human disturbance. Soil organic matter and soil microbes decreased more than 50% and 90%, respectively, and soil bulk density increased from 0.9 to 1.21 g x cm(-3) with increasing soil depth. Ditch edge level also affected the dynamics of soil factors under the same disturbance, with a better soil ecological condition at low-than at high ditch edge level.

  3. Effects of human disturbance on cave-nesting seabirds: the case of the storm petrel

    Science.gov (United States)

    Soldatini, Cecilia; Albores-Barajas, Yuri V.; Tagliavia, Marcello; Massa, Bruno; Fusani, Leonida; Canoine, Virginie

    2015-01-01

    Human disturbance is an important stress factor with potentially strong impact on breeding activity in animals. The consequences can be extinction of the breeding population, because disturbed animals might desert their breeding area and find no suitable substitute area. In this study, we investigated the effects of anthropogenic disturbance on a breeding population of Mediterranean storm petrels. Seabirds are increasingly used as bio-indicators for sea environmental parameters, because they are very sensitive to changing conditions. Burrowing or cave-nesting species may be particularly susceptible to human disturbance because their direct contact with humans is usually minimal or absent. First, we compared two different populations (exposed or not exposed to human disturbance) for their individual stress response to a standardized stressor (handling and keeping in a cloth bag). Second, we compared the two sub-colonies for their population-level stress response. Third, we tested experimentally whether sub-colonies of storm petrels exposed to tourism have physiological adaptations to anthropogenic disturbances. Our results indicate that storm petrels may be habituated to moderate disturbance associated with boat traffic close to the colony. PMID:27293726

  4. Reactions of chamois to human disturbance in Berchtesgaden National Park

    Directory of Open Access Journals (Sweden)

    Bögel, R.

    2002-12-01

    Full Text Available The objective of this study was to test whether the source and frequence of disturbance result in different behavioural responses of Chamois and if practical management guidelines can be drawn from these findings. The results clearly indicate that type and frequency of the disturbance have a strong influence on the behavioural response and that the disturbance tolerance varies with season, time of the day, sex and group size. Disturbances from flying resulted in a much stronger response than disturbances from the ground, and the response increased with velocity and/or noise level of the disturbance source. In areas with frequent disturbances the behavioural response was reduced when compared with remote areas, indicating habituation effects. While distance at first reaction and flight distance varied with disturbance intensity, the length of the flight path was not influenced by the disturbance type and frequency. Habitat use was also affected by disturbances: postdisturbance habitat types were mainly rocks and forests indicating a shift in habitat selection towards inaccessible habitat types or habitat types with good cover.

    [fr]
    Chez les chamois, nous avons étudié l’influence des différentes perturbations de diverses fréquences sur le comportement et nous nous sommes demandés si les résultats obtenus pouvaient orienter la gestion des populations. En effet, aussi bien le type que la fréquence de la perturbation ont influencé de manière significative le comportement. De plus, la tolérance aux perturbations varie avec la saison, l'heure du jour, le sexe et la taille du groupe. Les perturbations produites par des engins aériens ont provoqué une réponse beaucoup plus forte que celles provenant du terrain; la réponse étant augmentée avec la vitesse ou le degré du bruit de la source de perturbation. Là où les perturbations étaient fréquentes, la réponse se voyait réduite par rapport a des territoires

  5. The alteration of human sleep and circadian rhythms during spaceflight.

    Science.gov (United States)

    Gundel, A; Polyakov, V V; Zulley, J

    1997-03-01

    Numerous anecdotes in the past suggest the concept that sleep disturbances in astronauts occur more frequently during spaceflight than on ground. Such disturbances may be caused in part by exogenous factors, but also an altered physiological state under microgravity may add to reducing sleep quality in a spacecraft. The present investigation aims at a better understanding of possible sleep disturbances under microgravity. For the first time, experiments were conducted in which sleep and circadian regulation could be simultaneously assessed in space. Four astronauts took part in this study aboard the Russian MIR station. Sleep was recorded polygraphically on tape together with body temperature. For a comparison, the same parameters were measured during baseline periods preceding the flights. The circadian phase of body temperature was found to be delayed by about 2 h in space compared with baseline data. A free-run was not observed during the first 30 d in space. Sleep was shorter and more disturbed than on earth. In addition, the structure of sleep was significantly altered. In space, the latency to the first REM episode was shorter, and slow-wave sleep was redistributed from the first to the second sleep cycle. Several mechanisms may be responsible for these alterations in sleep regulation and circadian phase. Most likely, altered circadian zeitgebers on MIR and a deficiency in the process S of Borbély's sleep model cause the observed findings. The change in process S may be related to changes in physical activity as a result of weightlessness.

  6. [Effect of human disturbance on ecological stoichiometry characteristics of soil carbon, nitrogen and phosphorus in Minjiang River estuarine wetland].

    Science.gov (United States)

    Wang, Wei-Qi; Zeng, Cong-Sheng; Zhong, Chun-Qi; Tong, Chuan

    2010-10-01

    To clarify responses of soil ecological stoichiometry in wetland to human disturbance, the ecological stoichiometry characteristics of carbon, nitrogen and phosphorus elements of soil in Phragmites australis marsh, grassland, flat breed aquatics, cropland, pond aquaculture after human disturbance and abandoned cropland after human disturbance restoration in Minjiang River estuary were analyzed. The results showed: averaged values of C/N, C/P, N/P ratios were declined as the human disturbance increment, which appeared that Phragmites australis marsh, grassland (lower human disturbance, 25.53, 156.06, 6.11 and 27.58, 158.99, 5.78) were bigger than flat breed aquatics (medium human disturbance, 25.02, 96.90, 3.87), and flat breed aquatics (medium human disturbance) were bigger than cropland, pond aquaculture (higher human disturbance, 17.55, 46.19, 2.65 and 22.30, 57.51, 2.62). Compared with cropland, C/N, C/P, N/P ratios in abandoned cropland (human disturbance restoration) were (19.95, 63.81, 3.18) higher. The influencing factors were changed with the human disturbance intensity. Soil C/N ratios showed relatively small variation between different human disturbance and soil depth, while C/P and N/P ratios showed a high heterogeneity. The ratio of carbon to nutrition had preferable indication for carbon storage.

  7. Human disturbance provides foraging opportunities for birds in primary subalpine forest

    DEFF Research Database (Denmark)

    DuBay, Shane G.; Hart Reeve, Andrew; Wu, Yongjie

    2017-01-01

    to species that naturally occur in edge, open, or disturbed habitats. With observations and experiments we provide evidence of insectivorous birds exploiting human disturbance in primary subalpine forest in the mountains of southern China, displaying behavioral flexibility to gain novel foraging...... or Cettia major, and Heteroxenicus stellatus. This behavior is likely a modification of pre-existing interspecific foraging associations with pheasants and large mammals in the region. These larger animals disturb the earth and lower vegetation layers upon passage and while foraging, exposing previously...

  8. Phylogenetic impoverishment of plant communities following chronic human disturbances in the Brazilian Caatinga.

    Science.gov (United States)

    Ribeiro, Elâine M S; Santos, Bráulio A; Arroyo-Rodríguez, Víctor; Tabarelli, Marcelo; Souza, Gustavo; Leal, Inara R

    2016-06-01

    Chronic disturbances, such as selective logging, firewood extraction and extensive grazing, may lead to the taxonomic and phylogenetic impoverishment of remaining old-growth forest communities worldwide; however, the empirical evidence on this topic is limited. We tested this hypothesis in the Caatinga vegetation--a seasonally dry tropical forest restricted to northeast Brazil. We sampled 11,653 individuals (adults, saplings, and seedlings) from 51 species in 29 plots distributed along a gradient of chronic disturbance. The gradient was assessed using a chronic disturbance index (CDI) based on five recognized indicators of chronic disturbances: proximity to urban center, houses and roads and the density of both people and livestock. We used linear models to test if mean effective number of lineages, mean phylogenetic distance and phylogenetic dispersion decreased with CDI and if such relationships differed among ontogenetic stages. As expected, the mean effective number of lineages and the mean phylogenetic distance were negatively related to CDI, and such diversity losses occurred irrespective of ontogeny. Yet the increase in phylogenetic clustering in more disturbed plots was only evident in seedlings and saplings, mostly because clades with more descendent taxa than expected by chance (e.g., Euphorbiaceae) thrived in more disturbed plots. This novel study indicates that chronic human disturbances are promoting the phylogenetic impoverishment of the irreplaceable woody flora of the Brazilian Caatinga forest. The highest impoverishment was observed in seedlings and saplings, indicating that if current chronic disturbances remain, they will result in increasingly poorer phylogenetically forests. This loss of evolutionary history will potentially limit the capacity of this ecosystem to respond to human disturbances (i.e., lower ecological resilience) and particularly their ability to adapt to rapid climatic changes in the region.

  9. Using Landsat time series for characterizing forest disturbance dynamics in the coupled human and natural systems of Central Europe

    Science.gov (United States)

    Senf, Cornelius; Pflugmacher, Dirk; Hostert, Patrick; Seidl, Rupert

    2017-08-01

    Remote sensing is a key information source for improving the spatiotemporal understanding of forest ecosystem dynamics. Yet, the mapping and attribution of forest change remains challenging, particularly in areas where a number of interacting disturbance agents simultaneously affect forest development. The forest ecosystems of Central Europe are coupled human and natural systems, with natural and human disturbances affecting forests both individually and in combination. To better understand the complex forest disturbance dynamics in such systems, we utilize 32-year Landsat time series to map forest disturbances in five sites across Austria, the Czech Republic, Germany, Poland, and Slovakia. All sites consisted of a National Park and the surrounding forests, reflecting three management zones of different levels of human influence (managed, protected, strictly protected). This allowed for a comparison of spectral, temporal, and spatial disturbance patterns across a gradient from natural to coupled human and natural disturbances. Disturbance maps achieved overall accuracies ranging from 81% to 93%. Disturbance patches were generally small, with 95% of the disturbances being smaller than 10 ha. Disturbance rates ranged from 0.29% yr-1 to 0.95% yr-1, and differed substantially among management zones and study sites. Natural disturbances in strictly protected areas were longer in duration (median of 8 years) and slightly less variable in magnitude compared to human-dominated disturbances in managed forests (median duration of 1 year). However, temporal dynamics between natural and human-dominated disturbances showed strong synchrony, suggesting that disturbance peaks are driven by natural events affecting managed and unmanaged areas simultaneously. Our study demonstrates the potential of remote sensing for mapping forest disturbances in coupled human and natural systems, such as the forests of Central Europe. Yet, we also highlight the complexity of such systems in terms

  10. Structurally Altered Hard Coal in the Areas of Tectonic Disturbances - An Initial Attempt at Classification

    Science.gov (United States)

    Godyń, Katarzyna

    2016-09-01

    As regards the exploitation of hard coal seams, the near-fault zones and faults themselves are considered to be particularly dangerous areas, which is due to a high probability of the occurrence of gasogeodynamic phenomena. Tectonic dislocations running across a seam have a destructive impact on coal. Degradation of the coal structure, particularly visible in the microscale, is reflected in the coal's strength or gas properties. Such "structurally altered" coal is characterized by the presence of numerous fracturings, crushed areas, or dislocations of some of its fragments, and sometimes even the total destruction of the original structure. The present paper provides a detailed analysis and description of near-fault coal obtained from selected seams of the Upper Silesian Coal Basin, completed due to the application of optical methods. Both the type and the degree of changes in the structure of such coal were identified. On this basis, the author attempted to systematize the nomenclature used in relation to selected Upper Silesian hard coal seams, which, in turn, resulted in a proposed classification of the "altered structures" of the near-fault coal.

  11. Temporally and spatially partitioned behaviours of spinner dolphins: implications for resilience to human disturbance

    Science.gov (United States)

    Johnston, David W.; Christiansen, Fredrik

    2017-01-01

    Selective forces shape the evolution of wildlife behavioural strategies and influence the spatial and temporal partitioning of behavioural activities to maximize individual fitness. Globally, wildlife is increasingly exposed to human activities which may affect their behavioural activities. The ability of wildlife to compensate for the effects of human activities may have implications for their resilience to disturbance. Resilience theory suggests that behavioural systems which are constrained in their repertoires are less resilient to disturbance than flexible systems. Using behavioural time-series data, we show that spinner dolphins (Stenella longirostris) spatially and temporally partition their behavioural activities on a daily basis. Specifically, spinner dolphins were never observed foraging during daytime, where resting was the predominant activity. Travelling and socializing probabilities were higher in early mornings and late afternoons when dolphins were returning from or preparing for nocturnal feeding trips, respectively. The constrained nature of spinner dolphin behaviours suggests they are less resilient to human disturbance than other cetaceans. These dolphins experience the highest exposure rates to human activities ever reported for any cetaceans. Over the last 30 years human activities have increased significantly in Hawaii, but the spinner dolphins still inhabit these bays. Recent abundance estimates (2011 and 2012) however, are lower than all previous estimates (1979–1981, 1989–1992 and 2003), indicating a possible long-term impact. Quantification of the spatial and temporal partitioning of wildlife behavioural schedules provides critical insight for conservation measures that aim to mitigate the effects of human disturbance. PMID:28280561

  12. Insect avoidance may override human disturbances in reindeer habitat selection

    Directory of Open Access Journals (Sweden)

    Anna Skarin

    2004-04-01

    Full Text Available Habitat selection of semi-domesticated reindeer (Rangifer tarandus tarandus was investigated through faecal pellet- group counts and by direct observations of reindeer from helicopter in the Långfjället area in Idre reindeer herding district (62˚10’N and in Mittådalen reindeer herding district (62˚50’N, aerial observations only. Reindeer pellets were found to be most abundant in habitats at high altitudes, and in some vegetation types. Pellet-group densities tended to be higher near the tourist trails, which often follow higher altitudes in the terrain. The aerial surveys showed that the reindeer moved towards higher altitudes when the wind speed was low and the temperature was high both in June and July. In June they moved towards lower regions when temperature was low and the wind speed was strong. The conclusion is that the reindeer use Långfjället to escape insect harassment and warm weather, even though disturbance by tourism sometimes is high.Abstract in Swedish / Sammanfattning:Habitatval hos tamren (Rangifer tarandus tarandus undersöktes genom att göra en spillningsinventering och genom att göra flygobservationer från helikopter. Studien gjordes på Långfjället (62˚10’N i Idre nya sameby och i Mittådalens samebys sommarbetesområde (62˚50’N, endast flygobservationer. På Långfjället finns det vandringsleder som är frekventerade av vandrare från juni månad fram till september. Spillningen visade att renarna föredrog höjderna i området samt en del av vegetationstyperna. Det var också mer spillning närmare vandringslederna. Detta kan förklaras av att vandringslederna följer höjderna i terrängen. Flyginventeringarna under både juni och juli visade att renarna rörde sig mot högre terräng när det var varmt och lugnt väder. I juni rörde dom sig också i lägre terräng när det var stark vind och kallt väder. Slutsatsen är att renarna väljer att vistas i högre terräng för att undvika st

  13. Human disturbance influences reproductive success and growth rate in California sea lions (Zalophus californianus).

    Science.gov (United States)

    French, Susannah S; González-Suárez, Manuela; Young, Julie K; Durham, Susan; Gerber, Leah R

    2011-03-16

    The environment is currently undergoing changes at both global (e.g., climate change) and local (e.g., tourism, pollution, habitat modification) scales that have the capacity to affect the viability of animal and plant populations. Many of these changes, such as human disturbance, have an anthropogenic origin and therefore may be mitigated by management action. To do so requires an understanding of the impact of human activities and changing environmental conditions on population dynamics. We investigated the influence of human activity on important life history parameters (reproductive rate, and body condition, and growth rate of neonate pups) for California sea lions (Zalophus californianus) in the Gulf of California, Mexico. Increased human presence was associated with lower reproductive rates, which translated into reduced long-term population growth rates and suggested that human activities are a disturbance that could lead to population declines. We also observed higher body growth rates in pups with increased exposure to humans. Increased growth rates in pups may reflect a density dependent response to declining reproductive rates (e.g., decreased competition for resources). Our results highlight the potentially complex changes in life history parameters that may result from human disturbance, and their implication for population dynamics. We recommend careful monitoring of human activities in the Gulf of California and emphasize the importance of management strategies that explicitly consider the potential impact of human activities such as ecotourism on vertebrate populations.

  14. Human disturbance influences reproductive success and growth rate in California sea lions (Zalophus californianus.

    Directory of Open Access Journals (Sweden)

    Susannah S French

    Full Text Available The environment is currently undergoing changes at both global (e.g., climate change and local (e.g., tourism, pollution, habitat modification scales that have the capacity to affect the viability of animal and plant populations. Many of these changes, such as human disturbance, have an anthropogenic origin and therefore may be mitigated by management action. To do so requires an understanding of the impact of human activities and changing environmental conditions on population dynamics. We investigated the influence of human activity on important life history parameters (reproductive rate, and body condition, and growth rate of neonate pups for California sea lions (Zalophus californianus in the Gulf of California, Mexico. Increased human presence was associated with lower reproductive rates, which translated into reduced long-term population growth rates and suggested that human activities are a disturbance that could lead to population declines. We also observed higher body growth rates in pups with increased exposure to humans. Increased growth rates in pups may reflect a density dependent response to declining reproductive rates (e.g., decreased competition for resources. Our results highlight the potentially complex changes in life history parameters that may result from human disturbance, and their implication for population dynamics. We recommend careful monitoring of human activities in the Gulf of California and emphasize the importance of management strategies that explicitly consider the potential impact of human activities such as ecotourism on vertebrate populations.

  15. Human physiological reaction to geomagnetic disturbances of solar origin

    Science.gov (United States)

    Dimitrova, Sv.; Stoilova, I.

    2002-12-01

    During the last two decades publications about the influence of geomagnetic activity on human health increase but there are not still strong evidences for this relationship. We performed measurements and observations of 86 working volunteers during the period of autumn and spring equinox. We examined systolic, diastolic blood pressure and pulse rate. We also collected data for some personal health condition complaints. Four-way analyses of variance (MANOVA method) were employed and the influence of factors geomagnetic activity level, sequence of the days of measurements with respect to the increased geomagnetic activity, medicaments and sex was investigated. We also performed three-way analyses of variance and investigated influence of atmospheric pressure, medicaments and sex on the physiological parameters under consideration. Our investigations indicate that most of the persons examined irrespectively to their health status could be sensitive to the geomagnetic changes, which influence directly self-confidence and working ability.

  16. Thalamic alterations in preterm neonates and their relation to ventral striatum disturbances revealed by a combined shape and pose analysis.

    Science.gov (United States)

    Lao, Yi; Wang, Yalin; Shi, Jie; Ceschin, Rafael; Nelson, Marvin D; Panigrahy, Ashok; Leporé, Natasha

    2016-01-01

    Finding the neuroanatomical correlates of prematurity is vital to understanding which structures are affected, and to designing efficient prevention and treatment strategies. Converging results reveal that thalamic abnormalities are important indicators of prematurity. However, little is known about the localization of the abnormalities within the subnuclei of the thalamus, or on the association of altered thalamic development with other deep gray matter disturbances. Here, we aim to investigate the effect of prematurity on the thalamus and the putamen in the neonatal brain, and further investigate the associated abnormalities between these two structures. Using brain structural magnetic resonance imaging, we perform a novel combined shape and pose analysis of the thalamus and putamen between 17 preterm (41.12 ± 5.08 weeks) and 19 term-born (45.51 ± 5.40 weeks) neonates at term equivalent age. We also perform a set of correlation analyses between the thalamus and the putamen, based on the surface and pose results. We locate significant alterations on specific surface regions such as the anterior and ventral anterior (VA) thalamic nuclei, and significant relative pose changes of the left thalamus and the right putamen. In addition, we detect significant association between the thalamus and the putamen for both surface and pose parameters. The regions that are significantly associated include the VA, and the anterior and inferior putamen. We detect statistically significant surface deformations and pose changes on the thalamus and putamen, and for the first time, demonstrate the feasibility of using relative pose parameters as indicators for prematurity in neonates. Our methods show that regional abnormalities of the thalamus are associated with alterations of the putamen, possibly due to disturbed development of shared pre-frontal connectivity. More specifically, the significantly correlated regions in these two structures point to frontal

  17. Compensation of Magnetic Disturbances Improves Inertial and Magnetic Sensing of Human Body Segment Orientation

    NARCIS (Netherlands)

    Roetenberg, Daniel; Luinge, Henk; Baten, Chris T.M.; Veltink, Peter H.

    2005-01-01

    This paper describes a complementary Kalman filter design to estimate orientation of human body segments by fusing gyroscope, accelerometer, and magnetometer signals from miniature sensors. Ferromagnetic materials or other magnetic fields near the sensor module disturb the local earth magnetic field

  18. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds.

    Science.gov (United States)

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a 'wildlife photographer', resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds.

  19. Using the risk-disturbance hypothesis to assess the relative effects of human disturbance and predation risk on foraging American Oystercatchers

    Science.gov (United States)

    Peters, K.A.; Otis, D.L.

    2005-01-01

    The risk-disturbance hypothesis asserts that animals perceive human disturbance similar to nonlethal predation stimuli, and exhibit comparable responses in the form of optimization tradeoffs. However, few studies have examined how natural predation risk factors interact with human-disturbance stimuli to elicit such responses. We observed American Oystercatcher (Haematopus palliatus) vigilance behavior from September-December 2002 on the Cape Romain National Wildlife Refuge, South Carolina. A set of models was constructed based on 340 focal-animal samples and models revealed relationships between vigilance behavior, predator density, and boat activity. Oystercatchers increased vigilance in response to aerial predators, particularly late in the season when predator species composition was dominated by Northern Harriers (Circus cyaneus). At a broader temporal scale, oystercatchers exhibited the highest vigilance rates during simultaneous peaks in boating disturbance and Osprey (Pandion haliaetus) activity. Due to this temporal overlap of stimuli, it is difficult to interpret what may have been driving the observed increased in vigilance. Foraging rates appeared to be primarily driven by habitat and tidal stage indicating that time lost to vigilance did not effectively reduce intake. Taken together, these findings provide some support for the risk-disturbance hypothesis, underscore the sensitivity of disturbance studies to temporal scale, and draw attention to the potential confounding effects of natural predation risk. ?? The Cooper Ornithological Society 2005.

  20. Titanium dioxide nanoparticles alter cellular morphology via disturbing the microtubule dynamics

    Science.gov (United States)

    Mao, Zhilei; Xu, Bo; Ji, Xiaoli; Zhou, Kun; Zhang, Xuemei; Chen, Minjian; Han, Xiumei; Tang, Qiusha; Wang, Xinru; Xia, Yankai

    2015-04-01

    Titanium dioxide (TiO2) nanoparticles (NPs) have been widely used in our daily lives, for example, in the areas of sunscreens, cosmetics, toothpastes, food products, and nanomedical reagents. Recently, increasing concern has been raised about their neurotoxicity, but the mechanisms underlying such toxic effects are still unknown. In this work, we employed a human neuroblastoma cell line (SH-SY5Y) to study the effects of TiO2 NPs on neurological systems. Our results showed that TiO2 NPs did not affect cell viability but induced noticeable morphological changes until 100 μg ml-1. Immunofluorescence detection showed disorder, disruption, retraction, and decreased intensity of the microtubules after TiO2 NPs treatment. Both α and β tubule expressions did not change in the TiO2 NP-treated group, but the percentage of soluble tubules was increased. A microtubule dynamic study in living cells indicated that TiO2 NPs caused a lower growth rate and a higher shortening rate of microtubules as well as shortened lifetimes of de novo microtubules. TiO2 NPs did not cause changes in the expression and phosphorylation state of tau proteins, but a tau-TiO2 NP interaction was observed. TiO2 NPs could interact with tubule heterodimers, microtubules and tau proteins, which led to the instability of microtubules, thus contributing to the neurotoxicity of TiO2 NPs.Titanium dioxide (TiO2) nanoparticles (NPs) have been widely used in our daily lives, for example, in the areas of sunscreens, cosmetics, toothpastes, food products, and nanomedical reagents. Recently, increasing concern has been raised about their neurotoxicity, but the mechanisms underlying such toxic effects are still unknown. In this work, we employed a human neuroblastoma cell line (SH-SY5Y) to study the effects of TiO2 NPs on neurological systems. Our results showed that TiO2 NPs did not affect cell viability but induced noticeable morphological changes until 100 μg ml-1. Immunofluorescence detection showed disorder

  1. Tolerance of disturbance by humans in long-time resident and recent colonist urban doves

    Institute of Scientific and Technical Information of China (English)

    Jemma Gendall; Alan Lill; Juliey Beckman

    2015-01-01

    Background:A critical trait for successful urban dwelling by birds is the ability to tolerate high levels of disturbing stimulation by humans. If such tolerance is partly acquired gradually after colonization, species with a long history of residence in cities are likely to be more tolerant of such stimulation than recent urban colonists, but this has not often been tested. Methods:We tested whether introduced Rock (Columba livia) and Spotted (Streptopelis chinensis) Doves, historically long-term residents of Melbourne, Australia, were more tolerant of disturbance by humans than the very recent colonist, the native Crested Pigeon (Ochyphaps lophotes) by comparing the Flight Initiation Distances (FID) and time allocations to vigilance during foraging of all three species in urban Melbourne. That al three species are members of the Columbiformes reduces the possibility that any species differences in tolerance are simply phylogenetic in origin. Results:Flight initiation distance was shorter in Rock Doves than in the other two species, which did not differ in approachability by a human. Rock Doves retreated from an approaching human mainly by walking a relatively short distance, Crested Pigeons mainly by running a relatively short distance and Spotted Doves primarily by flying a comparatively long distance. The time allocation to anti-predator vigilance of Rock Doves was smaller than that of the other two species, whose allocations were similar. Conclusions:The very recent colonist of eastern Melbourne, the Crested Pigeon, was not the least tolerant of disturbance by humans of the three related species. Natural selection for tolerance therefore probably cannot entirely explain the pattern of tolerance evident among these urban dove species and behavioural flexibility is probably involved. Length of residency in a city is not an infallible guide to a species’ level of tolerance of disturbance by humans.

  2. Tolerance of disturbance by humans in long-time resident and recent colonist urban doves

    Institute of Scientific and Technical Information of China (English)

    Jemma; Gendall; Alan; Lill; Juliey; Beckman

    2015-01-01

    Background: A critical trait for successful urban dwelling by birds is the ability to tolerate high levels of disturbing stimulation by humans. If such tolerance is partly acquired gradually after colonization, species with a long history of residence in cities are likely to be more tolerant of such stimulation than recent urban colonists, but this has not often been tested.Methods: We tested whether introduced Rock(Columba livia) and Spotted(Streptopelis chinensis) Doves, historically long-term residents of Melbourne, Australia, were more tolerant of disturbance by humans than the very recent colonist, the native Crested Pigeon(Ochyphaps lophotes) by comparing the Flight Initiation Distances(FID) and time allocations to vigilance during foraging of all three species in urban Melbourne. That all three species are members of the Columbiformes reduces the possibility that any species differences in tolerance are simply phylogenetic in origin.Results: Flight initiation distance was shorter in Rock Doves than in the other two species, which did not differ in approachability by a human. Rock Doves retreated from an approaching human mainly by walking a relatively short distance, Crested Pigeons mainly by running a relatively short distance and Spotted Doves primarily by flying a comparatively long distance. The time allocation to anti-predator vigilance of Rock Doves was smaller than that of the other two species, whose allocations were similar.Conclusions: The very recent colonist of eastern Melbourne, the Crested Pigeon, was not the least tolerant of disturbance by humans of the three related species. Natural selection for tolerance therefore probably cannot entirely explain the pattern of tolerance evident among these urban dove species and behavioural flexibility is probably involved. Length of residency in a city is not an infallible guide to a species’ level of tolerance of disturbance by humans.

  3. Human-chromosome alterations induced by argon laser treatment

    Energy Technology Data Exchange (ETDEWEB)

    Simi, S.; Colella, C. (Consiglio Nazionale delle Ricerche, Pisa (Italy). Lab. di Mutagenesi e Differenziamento); Agati, G.; Fusi, F. (Florence Univ. (Italy). Ist. di Farmacologia); Corsi, M.F.; Pratesi, R. (Consiglio Nazionale delle Ricerche, Florence (Italy). Lab. di Elettronica Quantistica); Tocco, G.A. (Naples Univ. (Italy). Ist. di Istologia ed Embrilogia)

    1984-07-01

    The possible occurrence of genetic damage arising from exposure of human cells to visible laser light has been evaluated in PHA-stimulated human lymphocytes. Aneuploidy and chromosome aberrations have been observed after exposure to an argon laser. These findings appear of special interest in view of the possible role of these chromosome alterations in carcinogenesis.

  4. Active disturbance rejection control based human gait tracking for lower extremity rehabilitation exoskeleton.

    Science.gov (United States)

    Long, Yi; Du, Zhijiang; Cong, Lin; Wang, Weidong; Zhang, Zhiming; Dong, Wei

    2017-03-01

    This paper presents an active disturbance rejection control (ADRC) based strategy, which is applied to track the human gait trajectory for a lower limb rehabilitation exoskeleton. The desired human gait trajectory is derived from the Clinical Gait Analysis (CGA). In ADRC, the total external disturbance can be estimated by the extended state observer (ESO) and canceled by the designed control law. The observer bandwidth and the controller bandwidth are determined by the practical principles. We simulated the proposed methodology in MATLAB. The numerical simulation shows the tracking error comparison and the estimated errors of the extended state observer. Two experimental tests were carried out to prove the performance of the algorithm presented in this paper. The experiment results show that the proposed ADRC behaves a better performance than the regular proportional integral derivative (PID) controller. With the proposed ADRC, the rehabilitation system is capable of tracking the target gait more accurately.

  5. Genetic alterations by human papillomaviruses in oncogenesis.

    Science.gov (United States)

    Lazo, P A; Gallego, M I; Ballester, S; Feduchi, E

    1992-03-30

    The integration sites in the cellular genome of human papillomavirus are located in chromosomal regions always associated with oncogenes or other known tumor phenotypes. Two regions, 8q24 and 12q13, are common to several cases of cervical carcinoma and can have integrated more than one type of papillomavirus DNA. These two chromosomal regions contain several genes implicated in oncogenesis. These observations strongly imply that viral integration sites of DNA tumor viruses can be used as the access point to chromosomal regions where genes implicated in the tumor phenotype are located, a situation similar to that of non-transforming retroviruses.

  6. Posture alters human resting-state.

    Science.gov (United States)

    Thibault, Robert T; Lifshitz, Michael; Jones, Jennifer M; Raz, Amir

    2014-09-01

    Neuroimaging is ubiquitous; however, neuroimagers seldom investigate the putative impact of posture on brain activity. Whereas participants in most psychological experiments sit upright, many prominent neuroimaging techniques (e.g., functional magnetic resonance imaging (fMRI)) require participants to lie supine. Such postural discrepancies may hold important implications for brain function in general and for fMRI in particular. We directly investigated the effect of posture on spontaneous brain dynamics by recording scalp electrical activity in four orthostatic conditions (lying supine, inclined at 45°, sitting upright, and standing erect). Here we show that upright versus supine posture increases widespread high-frequency oscillatory activity. Our electroencephalographic findings highlight the importance of posture as a determinant in neuroimaging. When generalizing supine imaging results to ecological human cognition, therefore, cognitive neuroscientists would benefit from considering the influence of posture on brain dynamics.

  7. Incorporating a disturbance observer with direct velocity feedback for control of human-induced vibrations

    Science.gov (United States)

    Nyawako, Donald; Reynolds, Paul; Hudson, Emma

    2016-04-01

    Feedback control strategies are desirable for disturbance rejection of human-induced vibrations in civil engineering structures as human walking forces cannot easily be measured. In relation to human-induced vibration control studies, most past researches have focused on floors and footbridges and the widely used linear controller implemented in the trials has been the direct velocity feedback (DVF) scheme. With appropriate compensation to enhance its robustness, it has been shown to be effective at damping out the problematic modes of vibration of the structures in which the active vibration control systems have been implemented. The work presented here introduces a disturbance observer (DOB) that is used with an outer-loop DVF controller. Results of analytical studies presented in this work based on the dynamic properties of a walkway bridge structure demonstrate the potential of this approach for enhancing the vibration mitigation performance offered by a purely DVF controller. For example, estimates of controlled frequency response functions indicate improved attenuation of vibration around the dominant frequency of the walkway bridge structure as well as at higher resonant frequencies. Controlled responses from three synthesized walking excitation forces on a walkway bridge structure model show that the inclusion of the disturbance observer with an outer loop DVF has potential to improve on the vibration mitigation performance by about 3.5% at resonance and 6-10% off-resonance. These are realised with hard constraints being imposed on the low frequency actuator displacements.

  8. Effect of human disturbance on the prey of tiger in the Chitwan National Park--implications for park management.

    Science.gov (United States)

    Bhattarai, Bishnu Prasad; Kindlmann, Pavel

    2013-12-15

    Chitwan National Park is surrounded by large settlements of people who exploit the areas where tigers and their prey occur. In this study, we measured the associations between the abundance of the prey of tiger with habitat, topographic, predator and human disturbance variables, using canonical correspondence analysis. We show that the abundance of hog deer is closely associated with areas of tall grassland and floodplains, while that of other ungulate species is associated with that of forests and short grasslands. Primates were mainly abundant in riverine and mixed forests. Abundances of most species, except hog deer and wild pig, were more closely associated with areas of forests than with open areas, because the latter were mainly occupied by humans and livestock. The presence of the species studied was closely associated with habitat and disturbance variables. Proximity of water holes was more closely associated with the presence of ungulates than primates. There were close associations between human disturbance and abundances of primates and muntjac, possibly because these species are more tolerant and adapted to human disturbance. However, the major prey species of tiger were negatively associated with human disturbance. As a consequence, human disturbance has resulted in a decline in the abundance of tigers and the lack of prey could result in their extinction in the Chitwan NP. Therefore, in terms of the conservation and management of the park, minimizing human disturbance of wildlife habitats and restoration of a buffer zone forest should be the prime objectives. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Motor disturbances in mice with deficiency of the sodium channel gene Scn8a show features of human dystonia.

    Science.gov (United States)

    Hamann, Melanie; Meisler, Miriam H; Richter, Angelika

    2003-12-01

    The med(J) mouse with twisting movements related to deficiency of the sodium channel Scn8a has been proposed as a model of kinesiogenic dystonia. This prompted us to examine the phenotype of these mice in more detail. By cortical electroencephalographic (EEG) recordings, we could not detect any changes, demonstrating that the motor disturbances are not epileptic in nature, an important similarity to human dystonia. The significantly decreased body weight of med(J) mice was related to reduced food intake. Observations in the open field and by video recordings revealed that the mice exhibit sustained abnormal postures and movements of limbs, trunk and tail not only during locomotor activity but also at rest. With the exception of the head tremor, the other motor impairments were persistent rather than paroxysmal. When several neurological reflexes were tested, alterations were restricted to the posture and righting reflexes. Results of the wire hang test confirmed the greatly reduced muscle strength in the med(J) mouse. In agreement with different types of human dystonia, biperiden, haloperidol and diazepam moderately reduced the severity of motor disturbances in med(J) mice. In view of the sodium channel deficiency in med(J) mice, the beneficial effects of the sodium channel blocker phenytoin was an unexpected finding. By immunohistochemical examinations, the density of nigral dopaminergic neurons was found to be unaltered, substantiating the absence of pathomorphological abnormalities within the brain of med(J) mice shown by previous studies. With the exception of muscle weakness, many of the features of the med(J) mouse are similar to human idiopathic dystonia.

  10. Experimental evidence that dispersal drives ant community assembly in human-altered ecosystems.

    Science.gov (United States)

    King, Joshua R; Tschinkel, Walter R

    2016-01-01

    A key shortcoming in our understanding of exotic species' success is that it is not known how post-introduction dispersal contributes to the success of exotic species and the reassembly of invaded communities. Exotic and native species face poorly understood competition-colonization trade-offs in heterogeneous landscapes of natural and anthropogenic habitats. We conducted three experiments that tested how ant queen behavior during dispersal affects community composition. Using experimental plots, we tested whether (1) different types of habitat disturbance and (2) different sizes of habitat disturbance affected the abundance of newly mated queens landing in the plots. The three most abundant species captured were the exotic fire ant Solenopsis invicta, and the native species Brachymyrmex depilis, and S. pergandei, respectively. When queens were considered collectively, more queens landed in plowed, sand-added, and roadside plots than in control or mow plots, in other words, in the more heavily disturbed plots. We also tested (3) the effect of habitat manipulations on the survival of newly mated fire ant queens (Solenopsis invicta). Soil disturbance (tilling), lack of shade, and removal (poisoning) of the ant community resulted in the greatest fire ant colony survivorship. Collectively, experiments revealed that both exotic and native newly mated ant queens select open, human-altered ecosystems for founding new colonies. The selection of such habitats by fire ant queens leads to their successful colony founding and ultimately to their dominance in those habitats. Selection of disturbed habitats is therefore advantageous for exotic species but is an ecological trap for native species because they do not often succeed in founding colonies in these habitats.

  11. Human activities change marine ecosystems by altering predation risk.

    Science.gov (United States)

    Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

    2016-01-01

    In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises. © 2015 John Wiley & Sons Ltd.

  12. Behavior Response of Greater Yellowlegs, Snowy Egrets and Mallards to Human Disturbance at Back Bay National Wildlife Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The study was conducted at Back Bay NWR, Virginia Beach, Virginia. The objective was to measure the effect of human disturbance on snowy egrets, female mallards, and...

  13. Germline genetic variants disturbing the Let-7/LIN28 double-negative feedback loop alter breast cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Ao-Xiang Chen

    2011-09-01

    Full Text Available Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7-induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300 demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR of 1.25 (P = 0.0091, which was successfully replicated in a second independent study (n = 1,156 with community-based controls. The combined P-value of the two studies was 8.0 × 10⁻⁵. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk.

  14. Germline genetic variants disturbing the Let-7/LIN28 double-negative feedback loop alter breast cancer susceptibility.

    Science.gov (United States)

    Chen, Ao-Xiang; Yu, Ke-Da; Fan, Lei; Li, Ji-Yu; Yang, Chen; Huang, A-Ji; Shao, Zhi-Ming

    2011-09-01

    Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP) located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7-induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300) demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR) of 1.25 (P = 0.0091), which was successfully replicated in a second independent study (n = 1,156) with community-based controls. The combined P-value of the two studies was 8.0 × 10⁻⁵. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk.

  15. Altered autophagy in human adipose tissues in obesity

    Science.gov (United States)

    Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat d...

  16. Coping with continuous human disturbance in the wild: insights from penguin heart rate response to various stressors

    Directory of Open Access Journals (Sweden)

    Viblanc Vincent A

    2012-07-01

    Full Text Available Abstract Background A central question for ecologists is the extent to which anthropogenic disturbances (e.g. tourism might impact wildlife and affect the systems under study. From a research perspective, identifying the effects of human disturbance caused by research-related activities is crucial in order to understand and account for potential biases and derive appropriate conclusions from the data. Results Here, we document a case of biological adjustment to chronic human disturbance in a colonial seabird, the king penguin (Aptenodytes patagonicus, breeding on remote and protected islands of the Southern ocean. Using heart rate (HR as a measure of the stress response, we show that, in a colony with areas exposed to the continuous presence of humans (including scientists for over 50 years, penguins have adjusted to human disturbance and habituated to certain, but not all, types of stressors. When compared to birds breeding in relatively undisturbed areas, birds in areas of high chronic human disturbance were found to exhibit attenuated HR responses to acute anthropogenic stressors of low-intensity (i.e. sounds or human approaches to which they had been subjected intensely over the years. However, such attenuation was not apparent for high-intensity stressors (i.e. captures for scientific research which only a few individuals experience each year. Conclusions Habituation to anthropogenic sounds/approaches could be an adaptation to deal with chronic innocuous stressors, and beneficial from a research perspective. Alternately, whether penguins have actually habituated to anthropogenic disturbances over time or whether human presence has driven the directional selection of human-tolerant phenotypes, remains an open question with profound ecological and conservation implications, and emphasizes the need for more knowledge on the effects of human disturbance on long-term studied populations.

  17. Effects of heliogeophysical disturbances on fluid properties of blood in humans

    Science.gov (United States)

    Varakin, Yu. Ya.; Ionova, V. G.; Sazanova, E. A.; Sergeenko, N. P.

    2014-12-01

    The hypothesis is tested stating that the possible causes of the biotropic effects in the human organism during heliogeophysical disturbances are an increase in catecholamine levels in blood and changes in blood-aggregative properties. The detected effects are statistically significant and indicate the possibility of the direct influence of physical processes during disturbances on blood cells. Physical processes, presumably determining the shifts in human organism, are discussed. It is supposed that, during the initial phase of the storm, one of the physical mechanisms of action of the external weak periodic signals appearing upon the noise can be stochastic resonance. Data is presented indicating that the second and the third harmonics of brain nervous structures resonance may be actually caused by the first harmonics of oscillations of the ionosphere Alfven resonator that are able to synchronize or desynchronize the electromagnetic oscillation rhythms of blood cells. The possibility of direct influence of the electromagnetic field fluctuations on the dynamics of aggregation and disaggregation processes of platelets and erythrocytes in the blood stream during the development of the storm proper is discussed.

  18. Cross-spectral coherence between geomagnetic disturbance and human cardiovascular variables at non-societal frequencies.

    Science.gov (United States)

    Watanabe, Y; Hillman, D C; Otsuka, K; Bingham, C; Breus, T K; Cornélissen, G; Halberg, F

    1994-01-01

    A 35-year-old cardiologist monitored himself with an automatic ABPM-630 (Colin Electronics) monitor, mostly at 15-minute intervals around-the-clock for three years with a few interruptions. In this subject with a family history of high blood pressure and stroke, a cross-spectral analysis revealed a statistically significant coherence at 27.7 days between systolic and diastolic blood pressure and heart rate vs. the geomagnetic disturbance index, Kp. A lesser peak in coherence was found for systolic blood pressure with Kp at a trial period of 4.16 days (P = 0.046). These results suggest that changes in geomagnetism may influence the human circulation, at least in the presence of familial cardiovascular disease risk, and they may do so at frequencies that have no precise human-made cyclic worldwide match.

  19. Dealing with Magnetic Disturbances in Human Motion Capture: A Survey of Techniques

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    Gabriele Ligorio

    2016-03-01

    Full Text Available Magnetic-Inertial Measurement Units (MIMUs based on microelectromechanical (MEMS technologies are widespread in contexts such as human motion tracking. Although they present several advantages (lightweight, size, cost, their orientation estimation accuracy might be poor. Indoor magnetic disturbances represent one of the limiting factors for their accuracy, and, therefore, a variety of work was done to characterize and compensate them. In this paper, the main compensation strategies included within Kalman-based orientation estimators are surveyed and classified according to which degrees of freedom are affected by the magnetic data and to the magnetic disturbance rejection methods implemented. By selecting a representative method from each category, four algorithms were obtained and compared in two different magnetic environments: (1 small workspace with an active magnetic source; (2 large workspace without active magnetic sources. A wrist-worn MIMU was used to acquire data from a healthy subject, whereas a stereophotogrammetric system was adopted to obtain ground-truth data. The results suggested that the model-based approaches represent the best compromise between the two testbeds. This is particularly true when the magnetic data are prevented to affect the estimation of the angles with respect to the vertical direction.

  20. Minor cognitive disturbances in old age - an early stage of dementia?; Die leichte kognitive Stoerung Vergesslichkeit im Alter - eine Vorstufe der Demenz?

    Energy Technology Data Exchange (ETDEWEB)

    Hoedl, A.K.; Bonelli, R.M.; Kapfhammer, H.P. [Universitaetsklinik fuer Psychiatrie, Karl-Franzens-Univ. Graz (Austria)

    2005-06-09

    In clinical practice, minor cognitive disturbances should not be neglected as they may be the first signs of a process that may in the end lead to a loss of cognitive skills and even to dementia. (orig.) [German] Alter und zunehmende Vergesslichkeit werden oft mit grosser Selbstverstaendlichkeit assoziiert. (''Bei Opa rieselt eben schon der Kalk.'') Dass sich hier ein schleichender Verlust der kognitiven Faehigkeiten bis hin zur Demenz ankuendigen kann, wird dabei verkannt. Fuer die Praxis ist es daher von grosser Bedeutung, bereits leichte kognitive Stoerungen richtig einzuschaetzen und bei Bedarf zu therapieren. (orig.)

  1. Cultural alteration of human teeth in the Mariana Islands.

    Science.gov (United States)

    Ikehara-Quebral, R; Douglas, M T

    1997-11-01

    Evidence of cultural dental modification in a precontact (pre-1521) skeletal sample from the Academy of Our Lady of Guam gymnasium site in Agana, Guam, is documented. Two of the four individuals recovered at the Academy Gym site exhibit modification of the maxillary teeth. One individual displays vertical incising of a single tooth, and the other exhibits horizontal abrading of the anterior teeth which may be a purposeful or an incidental alteration. Although deliberate alteration of the dentition, including tooth extraction, notching, filing, and drilling, has been documented in human groups worldwide, little has been written about these cultural practices in the Mariana Islands. Examination of the available literature on precontact human remains from the region reveals at least three patterns of dental incising and similar cases of dental abrasion. While the origins of these practices are not known, the presence and style of these cultural alterations may be sex-specific, cosmetic in nature, or an indication of status in a ranked society. Alternatively, they may signify membership in a particular group or lineage, or mark a rite of passage. Because the comparative samples are limited in number and small, and the provenience of many of the skeletons is obscure, temporal variation cannot be ruled out.

  2. The sympathetic nervous system alterations in human hypertension.

    Science.gov (United States)

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-03-13

    Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

  3. Human papillomavirus infection and fertility alteration: a systematic review.

    Science.gov (United States)

    Souho, Tiatou; Benlemlih, Mohamed; Bennani, Bahia

    2015-01-01

    HPV is the most prevalent sexually transmitted infection and its effect in cancer induction is well documented. HPV infections are mostly asymptomatic, but it is unclear whether HPV infections can result in alterations of reproductive health. To determine the relationship between human papillomavirus infections and reproductive health in both men and women. A systematic literature review was performed in PubMed and ScienceDirect data bases from January 1994 through August 2014. HPV infections are shown to be significantly associated to many adverse effects in the reproductive function. These adverse effects were reported in different levels from cells production to pregnancy and may be related to the infecting genotype. It appears from this study that HPV detection and genotyping could be of great value in infertility diagnosis at least in idiopathic infertility cases. Like for the risk of carcinogenesis, another classification of HPV regarding the risk of fertility alteration may be considered after deep investigations.

  4. Identification and characterization of retinoblastoma gene mutations disturbing apoptosis in human breast cancers

    Directory of Open Access Journals (Sweden)

    Berge Elisabet

    2010-07-01

    Full Text Available Abstract Background The tumor suppressor pRb plays a key role regulating cell cycle arrest, and disturbances in the RB1 gene have been reported in different cancer forms. However, the literature reports contradictory findings with respect to a pro - versus anti - apoptotic role of pRb, and the consequence of alterations in RB1 to chemotherapy sensitivity remains unclear. This study is part of a project investigating alterations in pivotal genes as predictive factors to chemotherapy sensitivity in breast cancer. Results Analyzing 73 locally advanced (stage III breast cancers, we identified two somatic and one germline single nucleotide changes, each leading to amino acid substitution in the pRb protein (Leu607Ile, Arg698Trp, and Arg621Cys, respectively. This is the first study reporting point mutations affecting RB1 in breast cancer tissue. In addition, MLPA analysis revealed two large multiexon deletions (exons 13 to 27 and exons 21 to 23 with the exons 21-23 deletion occurring in the tumor also harboring the Leu607Ile mutation. Interestingly, Leu607Ile and Arg621Cys point mutations both localize to the spacer region of the pRb protein, a region previously shown to harbor somatic and germline mutations. Multiple sequence alignment across species indicates the spacer to be evolutionary conserved. All three RB1 point mutations encoded nuclear proteins with impaired ability to induce apoptosis compared to wild-type pRb in vitro. Notably, three out of four tumors harboring RB1 mutations displayed primary resistance to treatment with either 5-FU/mitomycin or doxorubicin while only 14 out of 64 tumors without mutations were resistant (p = 0.046. Conclusions Although rare, our findings suggest RB1 mutations to be of pathological importance potentially affecting sensitivity to mitomycin/anthracycline treatment in breast cancer.

  5. Diet rapidly and reproducibly alters the human gut microbiome.

    Science.gov (United States)

    David, Lawrence A; Maurice, Corinne F; Carmody, Rachel N; Gootenberg, David B; Button, Julie E; Wolfe, Benjamin E; Ling, Alisha V; Devlin, A Sloan; Varma, Yug; Fischbach, Michael A; Biddinger, Sudha B; Dutton, Rachel J; Turnbaugh, Peter J

    2014-01-23

    Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

  6. Medical humanities and medical alterity in fiction and in life.

    Science.gov (United States)

    Hurwitz, Brian

    2015-01-01

    A widely accepted component of any answer to the question 'What is it to do good medical ethics?' is the commitment to benefit people's health, in principlist terminology, 'beneficence'. This paper addresses deliberate maleficence and the cultural otherness with which it is associated, focusing on the activities of the serial killer Dr Harold Shipman. It finds an uncanny 'fit' between the normal operation of healthcare services and this sort of alterity which has attracted little attention from bioethicists but has been addressed by novelists. To the extent that the medical humanities offers useful insights into hard moral problems, its capacities rest on taking account of both the fictional and the real.

  7. Do Quercus ilex woodlands undergo abrupt non-linear functional changes in response to human disturbance along a climatic gradient?

    Science.gov (United States)

    Bochet, Esther; García-Fayos, Patricio; José Molina, Maria; Moreno de las Heras, Mariano; Espigares, Tíscar; Nicolau, Jose Manuel; Monleon, Vicente

    2017-04-01

    Theoretical models predict that drylands are particularly prone to suffer critical transitions with abrupt non-linear changes in their structure and functions as a result of the existing complex interactions between climatic fluctuations and human disturbances. However, so far, few studies provide empirical data to validate these models. We aim at determining how holm oak (Quercus ilex) woodlands undergo changes in their functions in response to human disturbance along an aridity gradient (from semi-arid to sub-humid conditions), in eastern Spain. For that purpose, we used (a) remote-sensing estimations of precipitation-use-efficiency (PUE) from enhanced vegetation index (EVI) observations performed in 231x231 m plots of the Moderate Resolution Imaging Spectroradiometer (MODIS); (b) biological and chemical soil parameter determinations (extracellular soil enzyme activity, soil respiration, nutrient cycling processes) from soil sampled in the same plots; (c) vegetation parameter determinations (ratio of functional groups) from vegetation surveys performed in the same plots. We analyzed and compared the shape of the functional change (in terms of PUE and soil and vegetation parameters) in response to human disturbance intensity for our holm oak sites along the aridity gradient. Overall, our results evidenced important differences in the shape of the functional change in response to human disturbance between climatic conditions. Semi-arid areas experienced a more accelerated non-linear decrease with an increasing disturbance intensity than sub-humid ones. The proportion of functional groups (herbaceous vs. woody cover) played a relevant role in the shape of the functional response of the holm oak sites to human disturbance.

  8. Evolving Human Alteration of the Carbon Cycle: the Watershed Continuum

    Science.gov (United States)

    Kaushal, S.; Delaney Newcomb, K.; Newcomer Johnson, T.; Pennino, M. J.; Smith, R. M.; Beaulieu, J. J.; Belt, K.; Grese, M.; Blomquist, J.; Duan, S.; Findlay, S.; Likens, G.; Mayer, P. M.; Murthy, S.; Utz, R.; Yepsen, M.

    2014-12-01

    Watersheds experiencing land development are constantly evolving, and their biogeochemical signatures are expected to evolve across both space and time in drainage waters. We investigate how land development influences spatial and temporal evolution of the carbon cycle from small streams to major rivers in the Eastern U.S. Along the watershed continuum, we show that there is spatial evolution in: (1) the amount, chemical form, and bioavailability of carbon; (2) carbon retention/release at the reach scale; and (3) ecosystem metabolism of carbon from headwaters to coastal waters. Over shorter time scales, the interaction between land use and climate variability alters magnitude and frequency of carbon "pulses" in watersheds. Amounts and forms of carbon pulses in agricultural and urban watersheds respond similarly to climate variability due to headwater alteration and loss of ecosystem services to buffer runoff and temperature changes. Over longer time scales, land use change has altered organic carbon concentrations in tidal waters of Chesapeake Bay, and there have been increased bicarbonate alkalinity concentrations in rivers throughout the Eastern U.S. due to human activities. In summary, our analyses indicates that the form and reactivity of carbon have evolved over space and time along the watershed continuum with major implications for downstream ecosystem metabolism, biological oxygen demand, carbon dioxide production, and river alkalinization.

  9. Earthworms as indicators for different forest management types and human disturbance in Ilam oak forest, Iran

    Directory of Open Access Journals (Sweden)

    Heydari Mehdi

    2014-09-01

    Full Text Available There has been observed widespread destruction of natural ecosystems around the world due to population growth, land use change and clear cutting which have affected soil properties. Different management strategies have been so far implemented to reduce this crisis in various regions of the world, such as e.g. short-term and long-term conservation management in the Zagros region. However, any management approach should be evaluated with appropriate measures to determine how managed areas respond. The main objective of the present study was to evaluate the potential of earthworms as an indicator for different forest management strategies and human disturbances in Zagros oak (Quercus persica Jaub. and Spach forest. The sites selected included undisturbed one as the control (Un, the sites under five-year conservation management (FCM and twenty-year conservation management (TCM as well as the disturbed site (D. The results of principal component analysis (PCA showed that different regions separated into the components: PC1 and PC2. Un and TCM sites gathered together and represented higher values of the factors such as pH, Kavailable, OC, clay content, Pavailable, CEC, overstory tree canopy, Ntot, biomass and abundance of earthworms. The positive direction of the first axis reflected a gradient of EC, BD and Ptot. According to the logistic model, NH4-N and EC played the most important role in earthworm presence and absence in Zagros forest ecosystem. Earthworm abundance and biomass could be a good indicator to evaluate different forest management strategies in the study area.

  10. Persistent organic pollutants alter DNA methylation during human adipocyte differentiation.

    Science.gov (United States)

    van den Dungen, Myrthe W; Murk, Albertinka J; Kok, Dieuwertje E; Steegenga, Wilma T

    2017-04-01

    Ubiquitous persistent organic pollutants (POPs) can accumulate in humans where they might influence differentiation of adipocytes. The aim of this study was to investigate whether DNA methylation is one of the underlying mechanisms by which POPs affect adipocyte differentiation, and to what extent DNA methylation can be related to gene transcription. Adipocyte differentiation was induced in two human cell models with continuous exposure to different POPs throughout differentiation. From the seven tested POPs, perfluorooctanesulfonic acid (PFOS) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreased lipid accumulation, while tributyltin (TBT) increased lipid accumulation. In human mesenchymal stem cells (hMSCs), TCDD and TBT induced opposite gene expression profiles, whereas after PFOS exposure gene expression remained relatively stable. Genome-wide DNA methylation analysis showed that all three POPs affected DNA methylation patterns in adipogenic and other genes, possibly related to the phenotypic outcome, but without concomitant gene expression changes. Differential methylation was predominantly detected in intergenic regions, where the biological relevance of alterations in DNA methylation is unclear. This study demonstrates that POPs, at environmentally relevant levels, are able to induce differential DNA methylation in human differentiating adipocytes. Copyright © 2017 Wageningen University. Published by Elsevier Ltd.. All rights reserved.

  11. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Xiufeng; Zhang, Ting; Wang, Jie; Li, Meng; Zhang, Xiaolei; Tu, Jing [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Sun, Shiqin [College of Pharmacy, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319 (China); Chen, Xiangmei, E-mail: xm_chen6176@bjmu.edu.cn [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Lu, Fengmin [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China)

    2014-04-25

    Highlights: • The expression of Fbx4 was significantly lower in HCC tissues. • Novel splicing variants of Fbx4 were identified. • These novel variants are much more abundant in human cancer tissues and cells. • The novel Fbx4 isoforms could promote cell proliferation and migration in vitro. • These isoforms showed less capability for cyclin D1 binding and degradation. - Abstract: Fbx4 is a specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. Two isoforms of human Fbx4 protein, the full length Fbx4α and the C-terminal truncated Fbx4β have been identified, but their functions remain elusive. In this study, we demonstrated that the mRNA level of Fbx4 was significantly lower in hepatocellular carcinoma tissues than that in the corresponding non-tumor tissues. More importantly, we identified three novel splicing variants of Fbx4: Fbx4γ (missing 168–245nt of exon1), Fbx4δ (missing exon6) and a N-terminal reading frame shift variant (missing exon2). Using cloning sequencing and RT-PCR, we demonstrated these novel splice variants are much more abundant in human cancer tissues and cell lines than that in normal tissues. When expressed in Sk-Hep1 and NIH3T3 cell lines, Fbx4β, Fbx4γ and Fbx4δ could promote cell proliferation and migration in vitro. Concordantly, these isoforms could disrupt cyclin D1 degradation and therefore increase cyclin D1 expression. Moreover, unlike the full-length isoform Fbx4α that mainly exists in cytoplasm, Fbx4β, Fbx4γ, and Fbx4δ locate in both cytoplasm and nucleus. Since cyclin D1 degradation takes place in cytoplasm, the nuclear distribution of these Fbx4 isoforms may not be involved in the down-regulation of cytoplasmic cyclin D1. These results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant

  12. Human-Induced Disturbance Alters Pollinator Communities in Tropical Mountain Forests

    Directory of Open Access Journals (Sweden)

    Matthias Schleuning

    2012-12-01

    Full Text Available Mountain forest ecosystems in the Andes are threatened by deforestation. Increasing fire frequencies lead to fire-degraded habitats that are often characterized by a persistent fern-dominated vegetation. Little is known about the consequences of these drastic changes in habitat conditions for pollinator communities. In a rapid diversity assessment, we collected individuals of two major groups of insect pollinators (bees and butterflies/moths with pan traps and compared pollinator diversities in a spatial block design between forest interior, forest edge and adjacent fire-degraded habitats at eight sites in the Bolivian Andes. We found that bee species richness and abundance were significantly higher in fire-degraded habitats than in forest habitats, whereas species richness and abundance of butterflies/moths increased towards the forests interior. Species turnover between forest and fire-degraded habitats was very high for both pollinator groups and was reflected by an increase in the body size of bee species and a decrease in the body size of butterfly/moth species in fire-degraded habitats. We conclude that deforestation by frequent fires has profound impacts on the diversity and composition of pollinator communities. Our tentative findings suggest shifts towards bee-dominated pollinator communities in fire-degraded habitats that may have important feedbacks on the regenerating communities of insect-pollinated plant species.

  13. Culture adaptation alters transcriptional hierarchies among single human embryonic stem cells reflecting altered patterns of differentiation.

    Science.gov (United States)

    Gokhale, Paul J; Au-Young, Janice K; Dadi, SriVidya; Keys, David N; Harrison, Neil J; Jones, Mark; Soneji, Shamit; Enver, Tariq; Sherlock, Jon K; Andrews, Peter W

    2015-01-01

    We have used single cell transcriptome analysis to re-examine the substates of early passage, karyotypically Normal, and late passage, karyotypically Abnormal ('Culture Adapted') human embryonic stem cells characterized by differential expression of the cell surface marker antigen, SSEA3. The results confirmed that culture adaptation is associated with alterations to the dynamics of the SSEA3(+) and SSEA3(-) substates of these cells, with SSEA3(-) Adapted cells remaining within the stem cell compartment whereas the SSEA3(-) Normal cells appear to have differentiated. However, the single cell data reveal that these substates are characterized by further heterogeneity that changes on culture adaptation. Notably the Adapted population includes cells with a transcriptome substate suggestive of a shift to a more naïve-like phenotype in contrast to the cells of the Normal population. Further, a subset of the Normal SSEA3(+) cells expresses genes typical of endoderm differentiation, despite also expressing the undifferentiated stem cell genes, POU5F1 (OCT4) and NANOG, whereas such apparently lineage-primed cells are absent from the Adapted population. These results suggest that the selective growth advantage gained by genetically variant, culture adapted human embryonic stem cells may derive in part from a changed substate structure that influences their propensity for differentiation.

  14. Past Human Disturbance Effects upon Biodiversity are Greatest in the Canopy; A Case Study on Rainforest Butterflies.

    Directory of Open Access Journals (Sweden)

    Andrew Whitworth

    Full Text Available A key part of tropical forest spatial complexity is the vertical stratification of biodiversity, with widely differing communities found in higher rainforest strata compared to terrestrial levels. Despite this, our understanding of how human disturbance may differentially affect biodiversity across vertical strata of tropical forests has been slow to develop. For the first time, how the patterns of current biodiversity vary between three vertical strata within a single forest, subject to three different types of historic anthropogenic disturbance, was directly assessed. In total, 229 species of butterfly were detected, with a total of 5219 individual records. Butterfly species richness, species diversity, abundance and community evenness differed markedly between vertical strata. We show for the first time, for any group of rainforest biodiversity, that different vertical strata within the same rainforest, responded differently in areas with different historic human disturbance. Differences were most notable within the canopy. Regenerating forest following complete clearance had 47% lower canopy species richness than regenerating forest that was once selectively logged, while the reduction in the mid-storey was 33% and at ground level, 30%. These results also show for the first time that even long term regeneration (over the course of 30 years may be insufficient to erase differences in biodiversity linked to different types of human disturbance. We argue, along with other studies, that ignoring the potential for more pronounced effects of disturbance on canopy fauna, could lead to the underestimation of the effects of habitat disturbance on biodiversity, and thus the overestimation of the conservation value of regenerating forests more generally.

  15. Past Human Disturbance Effects upon Biodiversity are Greatest in the Canopy; A Case Study on Rainforest Butterflies.

    Science.gov (United States)

    Whitworth, Andrew; Villacampa, Jaime; Brown, Alice; Huarcaya, Ruthmery Pillco; Downie, Roger; MacLeod, Ross

    2016-01-01

    A key part of tropical forest spatial complexity is the vertical stratification of biodiversity, with widely differing communities found in higher rainforest strata compared to terrestrial levels. Despite this, our understanding of how human disturbance may differentially affect biodiversity across vertical strata of tropical forests has been slow to develop. For the first time, how the patterns of current biodiversity vary between three vertical strata within a single forest, subject to three different types of historic anthropogenic disturbance, was directly assessed. In total, 229 species of butterfly were detected, with a total of 5219 individual records. Butterfly species richness, species diversity, abundance and community evenness differed markedly between vertical strata. We show for the first time, for any group of rainforest biodiversity, that different vertical strata within the same rainforest, responded differently in areas with different historic human disturbance. Differences were most notable within the canopy. Regenerating forest following complete clearance had 47% lower canopy species richness than regenerating forest that was once selectively logged, while the reduction in the mid-storey was 33% and at ground level, 30%. These results also show for the first time that even long term regeneration (over the course of 30 years) may be insufficient to erase differences in biodiversity linked to different types of human disturbance. We argue, along with other studies, that ignoring the potential for more pronounced effects of disturbance on canopy fauna, could lead to the underestimation of the effects of habitat disturbance on biodiversity, and thus the overestimation of the conservation value of regenerating forests more generally.

  16. Past Human Disturbance Effects upon Biodiversity are Greatest in the Canopy; A Case Study on Rainforest Butterflies

    Science.gov (United States)

    Whitworth, Andrew; Villacampa, Jaime; Brown, Alice; Huarcaya, Ruthmery Pillco; Downie, Roger; MacLeod, Ross

    2016-01-01

    A key part of tropical forest spatial complexity is the vertical stratification of biodiversity, with widely differing communities found in higher rainforest strata compared to terrestrial levels. Despite this, our understanding of how human disturbance may differentially affect biodiversity across vertical strata of tropical forests has been slow to develop. For the first time, how the patterns of current biodiversity vary between three vertical strata within a single forest, subject to three different types of historic anthropogenic disturbance, was directly assessed. In total, 229 species of butterfly were detected, with a total of 5219 individual records. Butterfly species richness, species diversity, abundance and community evenness differed markedly between vertical strata. We show for the first time, for any group of rainforest biodiversity, that different vertical strata within the same rainforest, responded differently in areas with different historic human disturbance. Differences were most notable within the canopy. Regenerating forest following complete clearance had 47% lower canopy species richness than regenerating forest that was once selectively logged, while the reduction in the mid-storey was 33% and at ground level, 30%. These results also show for the first time that even long term regeneration (over the course of 30 years) may be insufficient to erase differences in biodiversity linked to different types of human disturbance. We argue, along with other studies, that ignoring the potential for more pronounced effects of disturbance on canopy fauna, could lead to the underestimation of the effects of habitat disturbance on biodiversity, and thus the overestimation of the conservation value of regenerating forests more generally. PMID:26950438

  17. Long term repeated fire disturbance alters soil bacterial diversity but not the abundance in an Australian wet sclerophyll forest.

    Science.gov (United States)

    Shen, Ju-pei; Chen, C R; Lewis, Tom

    2016-01-20

    Effects of fire on biogeochemical cycling in terrestrial ecosystem are widely acknowledged, while few studies have focused on the bacterial community under the disturbance of long-term frequent prescribed fire. In this study, three treatments (burning every two years (B2), burning every four years (B4) and no burning (B0)) were applied for 38 years in an Australian wet sclerophyll forest. Results showed that bacterial alpha diversity (i.e. bacterial OTU) in the top soil (0-10 cm) was significantly higher in the B2 treatment compared with the B0 and B4 treatments. Non-metric multidimensional analysis (NMDS) of bacterial community showed clear separation of the soil bacterial community structure among different fire frequency regimes and between the depths. Different frequency fire did not have a substantial effect on bacterial composition at phylum level or bacterial 16S rRNA gene abundance. Soil pH and C:N ratio were the major drivers for bacterial community structure in the most frequent fire treatment (B2), while other factors (EC, DOC, DON, MBC, NH4(+), TC and TN) were significant in the less frequent burning and no burning treatments (B4 and B0). This study suggested that burning had a dramatic impact on bacterial diversity but not abundance with more frequent fire.

  18. Long term repeated fire disturbance alters soil bacterial diversity but not the abundance in an Australian wet sclerophyll forest

    Science.gov (United States)

    Shen, Ju-Pei; Chen, C. R.; Lewis, Tom

    2016-01-01

    Effects of fire on biogeochemical cycling in terrestrial ecosystem are widely acknowledged, while few studies have focused on the bacterial community under the disturbance of long-term frequent prescribed fire. In this study, three treatments (burning every two years (B2), burning every four years (B4) and no burning (B0)) were applied for 38 years in an Australian wet sclerophyll forest. Results showed that bacterial alpha diversity (i.e. bacterial OTU) in the top soil (0–10 cm) was significantly higher in the B2 treatment compared with the B0 and B4 treatments. Non-metric multidimensional analysis (NMDS) of bacterial community showed clear separation of the soil bacterial community structure among different fire frequency regimes and between the depths. Different frequency fire did not have a substantial effect on bacterial composition at phylum level or bacterial 16S rRNA gene abundance. Soil pH and C:N ratio were the major drivers for bacterial community structure in the most frequent fire treatment (B2), while other factors (EC, DOC, DON, MBC, NH4+, TC and TN) were significant in the less frequent burning and no burning treatments (B4 and B0). This study suggested that burning had a dramatic impact on bacterial diversity but not abundance with more frequent fire.

  19. Fluctuations and patterns of desert rodent communities under human disturbance: fluctuating tendency and sensitive response of their population

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The four kinds of sites under different kinds of human disturbances, i.e. a farmland area, a rotational-grazing area, an over-grazing area and a prohibited-grazing area, were selected in the typical region of the Alashan Desert of Inner Mongolia from April to October in 2002, 2003 and 2004 respectively. The fluctuating tendency of rodent communities and the sensitive response of their populations were studied using mark-recapture and trap-day methods. The four kinds of mark-recapture samples and line samples were taken in different human disturbance areas. The area of the mark-recapturing sample was 0.95 hm2 and that of the line sample was 10 km2. The samples were collected every month in the mark-recapturing sites for four consecutive days and in line sites in April, July and October every year. The variable matrix was composed of the numbers of captured rodents of the rodent communities. The sensitive response of the populations in the communities was analyzed with principal component analysis (PCA). Results showed that there were different types of rodent communities under different kinds of human disturbance on two scales in three years. In each scale, there were large differences in both the number of species and the number of main population in the rodent communities under different kinds of human disturbance on the farmland area and over-grazing area especially. The results of PCA showed that the sensitive response of the populations of the communities was significantly different under different kinds of human disturbance on the two scales in the three years. Cricetulus barabensis was the most sensitive on the farmland area, there were no differences in sensitive response of the various rodents on the rotational-grazing area, and Dipus sagitta and Phodopus roborovskii were the most sensitive in the over-grazing area.

  20. Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness.

    Science.gov (United States)

    Koethe, Dagmar; Gerth, Christoph W; Neatby, Miriam A; Haensel, Anita; Thies, Martin; Schneider, Udo; Emrich, Hinderk M; Klosterkötter, Joachim; Schultze-Lutter, Frauke; Leweke, F Markus

    2006-12-01

    Recent data on alterations of the endogenous cannabinoid system in schizophrenia have raised the question of its functional role in this disease. The psychoactive compound of Cannabis sativa, delta-9-tetrahydrocannabinol (Delta9-THC), has been shown to induce psychotic symptoms, but it is unknown to what extend prodromal states of psychoses are reflected by these experimental approaches. This study compares four groups of subjects: antipsychotic-naïve patients suffering from acute paranoid schizophrenic or schizophreniform psychosis (SZ), patients in the prodromal state (IPS), healthy controls without any pharmacological intervention (HC) and a second group of healthy volunteers who were orally administered synthetic Delta9-THC (Dronabinol) (HC-THC). Neither SZ and IPS nor HC received the experimental drug. All subjects were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Binocular Depth Inversion Illusion Test (BDII). The latter represents a sensitive measure of impaired visual information processing that manifests in various experimental and naturally occurring psychotic states. BDII values were well comparable in SZ, IPS and HC-THC, and all groups differed significantly to HC. The BPRS revealed no significant difference between HC-THC and IPS while both were significantly different from SZ and HC, respectively. Our results suggest that Delta9-THC-induced altered states of consciousness may serve as a useful tool for modeling psychotic disorders, particularly their prodromal states. Furthermore, they provide insight into the perceptual and psychopathological alterations induced by Delta9-THC, which is essential for the understanding of the pro-psychotic effects of herbal cannabis preparations with highly enriched Delta9-THC content.

  1. Metabolic state alters economic decision making under risk in humans.

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    Mkael Symmonds

    Full Text Available BACKGROUND: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores. Specifically, animals often express a preference for risky (more variable food sources when below a metabolic reference point (hungry, and safe (less variable food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. METHODOLOGY/PRINCIPAL FINDINGS: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake, and circulating leptin levels (providing an assay of energy reserves. We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. CONCLUSIONS/SIGNIFICANCE: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that

  2. Epigenetic Alterations in Density Selected Human Spermatozoa for Assisted Reproduction.

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    Bolan Yu

    Full Text Available Epidemiological evidence indicates that assisted reproductive technologies (ART may be associated with several epigenetic diseases such as Beckwith-Wiedemann syndrome (BWS or Silver-Russell syndrome (SRS. Selection of sperm by density-gradients in ART has improved DNA integrity and sperm quality; however, epigenetic alterations associated with this approach are largely unknown. In the present study, we investigated DNA methylation and histone retention profiles in raw sperm and selected sperm derived from the same individual and separated by using density-gradients. Results from a study group consisting of 93 males demonstrated that both global DNA methylation and histone retention levels decreased in density selected sperm. Compared to unselected raw sperm, histone transition rates decreased by an average of 27.2% in selected sperm, and the global methylation rate was 3.8% in unselected sperm and 3.3% in the selected sperm. DNA methylation and histone retention location profiling analyses suggested that these alterations displayed specific location patterns in the human genome. Changes in the pattern of hypomethylation largely occurred in transcriptional factor gene families such as HOX, FOX, and GATA. Histone retention increased in 67 genes, whereas it was significantly clustered in neural development-related gene families, particularly the olfactory sensor gene family. Although a causative relationship could not be established, the results of the present study suggest the possibility that sperm with good density also possess unique epigenetic profiles, particularly for genes involved in neural and olfactory development. As increasing evidence demonstrates that epigenetics plays a key role in embryonic development and offspring growth characteristics, the specific epigenetic alterations we observed in selected sperm may influence the transcriptional process and neural development in embryos.

  3. Do alterations in follicular fluid proteases contribute to human infertility?

    Science.gov (United States)

    Cookingham, Lisa Marii; Van Voorhis, Bradley J; Ascoli, Mario

    2015-05-01

    Cathepsin L and ADAMTS-1 are known to play critical roles in follicular rupture, ovulation, and fertility in mice. Similar studies in humans are limited; however, both are known to increase during the periovulatory period. No studies have examined either protease in the follicular fluid of women with unexplained infertility or infertility related to advanced maternal age (AMA). We sought to determine if alterations in cathepsin L and/or ADAMTS-1 existed in these infertile populations. Patients undergoing in vitro fertilization (IVF) for unexplained infertility or AMA-related infertility were prospectively recruited for the study; patients with tubal or male factor infertility were recruited as controls. Follicular fluid was collected to determine gene expression (via quantitative polymerase chain reaction), enzyme concentrations (via enzyme-linked immunosorbent assays), and enzymatic activities (via fluorogenic enzyme cleavage assay or Western blot analysis) of cathepsin L and ADAMTS-1. The analysis included a total of 42 patients (14 per group). We found no statistically significant difference in gene expression, enzyme concentration, or enzymatic activity of cathepsin L or ADAMTS-1 in unexplained infertility or AMA-related infertility as compared to controls. We also found no statistically significant difference in expression or concentration with advancing age. Cathepsin L and ADAMTS-1 are not altered in women with unexplained infertility or AMA-related infertility undergoing IVF, and they do not decline with advancing age. It is possible that differences exist in natural cycles, contributing to infertility; however, our findings do not support a role for protease alterations as a common cause of infertility.

  4. THE SYMPATHETIC NERVOUS SYSTEM ALTERATIONS IN HUMAN HYPERTENSION

    Science.gov (United States)

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-01-01

    A number of articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as “promoters” and “amplifiers” of human hypertension. We expand on the role of the sympathetic nervous system in two increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves. PMID:25767284

  5. Computational Hemodynamic Simulation of Human Circulatory System under Altered Gravity

    Science.gov (United States)

    Kim. Chang Sung; Kiris, Cetin; Kwak, Dochan

    2003-01-01

    A computational hemodynamics approach is presented to simulate the blood flow through the human circulatory system under altered gravity conditions. Numerical techniques relevant to hemodynamics issues are introduced to non-Newtonian modeling for flow characteristics governed by red blood cells, distensible wall motion due to the heart pulse, and capillary bed modeling for outflow boundary conditions. Gravitational body force terms are added to the Navier-Stokes equations to study the effects of gravity on internal flows. Six-type gravity benchmark problems are originally presented to provide the fundamental understanding of gravitational effects on the human circulatory system. For code validation, computed results are compared with steady and unsteady experimental data for non-Newtonian flows in a carotid bifurcation model and a curved circular tube, respectively. This computational approach is then applied to the blood circulation in the human brain as a target problem. A three-dimensional, idealized Circle of Willis configuration is developed with minor arteries truncated based on anatomical data. Demonstrated is not only the mechanism of the collateral circulation but also the effects of gravity on the distensible wall motion and resultant flow patterns.

  6. [Effects of human disturbance on soil aggregates content and their organic C stability in Karst regions].

    Science.gov (United States)

    Wei, Ya-wei; Su, Yi-rong; Chen, Xiang-bi; He, Xun-yang; Qin, Wen-geng; Wei, Guo-fu

    2011-04-01

    Taking the primary forest land (PF), natural restoration land (NR), grazing grassland burned annually in winter (GB), and maize-sweet potato cropland (MS) in Karst regions of Northwest Guangxi as test objects, this paper studied the soil aggregates content and their organic C stability in the four ecosystems under different human disturbance patterns. The soil water-stable aggregates (>0.25 mm) content in PF, NR, and GB accounted for more than 70%, while that in MS was only 37%. The destruction rate of soil aggregates structure in the four ecosystems decreased in the sequence of MS (54.9%) > GB (23.2%) > NR (9.8%) and PF (9.6%), with significant differences among them (Psoil aggregate organic C decreased after an initial increase and kept stable after 20 days, and increased with decreasing aggregate size. In the same size aggregates, the mineralization rate of organic C in the four ecosystems increased in the sequence of MS soil organic C was 1.7% - 3.8%, being significantly higher than that in NR, GB, and MS. The cumulative mineralization amount of soil organic C had the same change trend with the mineralization rate. The contents of soil organic C and aggregate organic C were significantly positively correlated with the mineralization rate and cumulative mineralization amount of organic C, respectively, and significantly negatively correlated with the mineralization ratio of organic C.

  7. Transcriptome Alterations In X-Irradiated Human Gingiva Fibroblasts.

    Science.gov (United States)

    Weissmann, Robert; Kacprowski, Tim; Peper, Michel; Esche, Jennifer; Jensen, Lars R; van Diepen, Laura; Port, Matthias; Kuss, Andreas W; Scherthan, Harry

    2016-08-01

    Ionizing radiation is known to induce genomic lesions, such as DNA double strand breaks, whose repair can lead to mutations that can modulate cellular and organismal fate. Soon after radiation exposure, cells induce transcriptional changes and alterations of cell cycle programs to respond to the received DNA damage. Radiation-induced mutations occur through misrepair in a stochastic manner and increase the risk of developing cancers years after the incident, especially after high dose radiation exposures. Here, the authors analyzed the transcriptomic response of primary human gingival fibroblasts exposed to increasing doses of acute high dose-rate x rays. In the dataset obtained after 0.5 and 5 Gy x-ray exposures and two different repair intervals (0.5 h and 16 h), the authors discovered several radiation-induced fusion transcripts in conjunction with dose-dependent gene expression changes involving a total of 3,383 genes. Principal component analysis of repeated experiments revealed that the duration of the post-exposure repair intervals had a stronger impact than irradiation dose. Subsequent overrepresentation analyses showed a number of KEGG gene sets and WikiPathways, including pathways known to relate to radioresistance in fibroblasts (Wnt, integrin signaling). Moreover, a significant radiation-induced modulation of microRNA targets was detected. The data sets on IR-induced transcriptomic alterations in primary gingival fibroblasts will facilitate genomic comparisons in various genotoxic exposure scenarios.

  8. Altered gene expression in human placenta after suspected preterm labour.

    Science.gov (United States)

    Oros, D; Strunk, M; Breton, P; Paules, C; Benito, R; Moreno, E; Garcés, M; Godino, J; Schoorlemmer, J

    2017-07-01

    Suspected preterm labour occurs in around 9% of pregnancies. However, almost two-thirds of women admitted for threatened preterm labour ultimately deliver at term and are considered risk-free for fetal development. We examined placental and umbilical cord blood samples from preterm or term deliveries after threatened preterm labour as well as term deliveries without threatened preterm labour. We quantitatively analysed the mRNA expression of inflammatory markers (IL6, IFNγ, and TNFα) and modulators of angiogenesis (FGF2, PGF, VEGFA, VEGFB, and VEGFR1). A total of 132 deliveries were analysed. Preterm delivery and term delivery after suspected preterm labour groups showed similar increases in TNFα expression compared with the term delivery control group in umbilical cord blood samples. Placental samples from preterm and term deliveries after suspected preterm labour exhibited significantly increased expression of TNFα and IL6 and decreased expression of IFNγ. Suspected preterm labour was also associated with altered expression of angiogenic factors, although not all differences reached statistical significance. We found gene expression patterns indicative of inflammation in human placentas after suspected preterm labour regardless of whether the deliveries occurred preterm or at term. Similarly, a trend towards altered expression of angiogeneic factors was not limited to preterm birth. These findings suggest that the biological mechanisms underlying threatened preterm labour affect pregnancies independently of gestational age at birth. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Portuguese propolis disturbs glycolytic metabolism of human colorectal cancer in vitro.

    Science.gov (United States)

    Valença, Isabel; Morais-Santos, Filipa; Miranda-Gonçalves, Vera; Ferreira, Ana Margarida; Almeida-Aguiar, Cristina; Baltazar, Fátima

    2013-07-19

    Propolis is a resin collected by bees from plant buds and exudates, which is further processed through the activity of bee enzymes. Propolis has been shown to possess many biological and pharmacological properties, such as antimicrobial, antioxidant, immunostimulant and antitumor activities. Due to this bioactivity profile, this resin can become an alternative, economic and safe source of natural bioactive compounds.Antitumor action has been reported in vitro and in vivo for propolis extracts or its isolated compounds; however, Portuguese propolis has been little explored. The aim of this work was to evaluate the in vitro antitumor activity of Portuguese propolis on the human colon carcinoma cell line HCT-15, assessing the effect of different fractions (hexane, chloroform and ethanol residual) of a propolis ethanol extract on cell viability, proliferation, metabolism and death. Propolis from Angra do Heroísmo (Azores) was extracted with ethanol and sequentially fractionated in solvents with increasing polarity, n-hexane and chloroform. To assess cell viability, cell proliferation and cell death, Sulforhodamine B, BrDU incorporation assay and Anexin V/Propidium iodide were used, respectively. Glycolytic metabolism was estimated using specific kits. All propolis samples exhibited a cytotoxic effect against tumor cells, in a dose- and time-dependent way. Chloroform fraction, the most enriched in phenolic compounds, appears to be the most active, both in terms of inhibition of viability and cell death. Data also show that this cytotoxicity involves disturbance in tumor cell glycolytic metabolism, seen by a decrease in glucose consumption and lactate production. Our results show that Portuguese propolis from Angra do Heroísmo (Azores) can be a potential therapeutic agent against human colorectal cancer.

  10. Portuguese propolis disturbs glycolytic metabolism of human colorectal cancer in vitro

    Science.gov (United States)

    2013-01-01

    Background Propolis is a resin collected by bees from plant buds and exudates, which is further processed through the activity of bee enzymes. Propolis has been shown to possess many biological and pharmacological properties, such as antimicrobial, antioxidant, immunostimulant and antitumor activities. Due to this bioactivity profile, this resin can become an alternative, economic and safe source of natural bioactive compounds. Antitumor action has been reported in vitro and in vivo for propolis extracts or its isolated compounds; however, Portuguese propolis has been little explored. The aim of this work was to evaluate the in vitro antitumor activity of Portuguese propolis on the human colon carcinoma cell line HCT-15, assessing the effect of different fractions (hexane, chloroform and ethanol residual) of a propolis ethanol extract on cell viability, proliferation, metabolism and death. Methods Propolis from Angra do Heroísmo (Azores) was extracted with ethanol and sequentially fractionated in solvents with increasing polarity, n-hexane and chloroform. To assess cell viability, cell proliferation and cell death, Sulforhodamine B, BrDU incorporation assay and Anexin V/Propidium iodide were used, respectively. Glycolytic metabolism was estimated using specific kits. Results All propolis samples exhibited a cytotoxic effect against tumor cells, in a dose- and time-dependent way. Chloroform fraction, the most enriched in phenolic compounds, appears to be the most active, both in terms of inhibition of viability and cell death. Data also show that this cytotoxicity involves disturbance in tumor cell glycolytic metabolism, seen by a decrease in glucose consumption and lactate production. Conclusion Our results show that Portuguese propolis from Angra do Heroísmo (Azores) can be a potential therapeutic agent against human colorectal cancer. PMID:23870175

  11. Alteration of Cell Cycle Mediated by Zinc in Human Bronchial ...

    Science.gov (United States)

    Zinc (Zn2+), a ubiquitous ambient air contaminant, presents an oxidant challenge to the human lung and is linked to adverse human health effects. To further elucidate the adaptive and apoptotic cellular responses of human airway cells to Zn2+, we performed pilot studies to examine cell cycle perturbation upon exposure using a normal human bronchial epithelial cell culture (BEAS-2B). BEAS-2B cells were treated with low (0, 1, 2 µM) and apoptotic (3 µM) doses of Zn2+ plus 1 µM pyrithione, a Zn2+-specific ionophore facilitating cellular uptake, for up to 24 h. Fixed cells were then stained with propidium iodine (PI) and cell cycle phase was determined by fluorescent image cytometry. Initial results report the percentage of cells in the S phase after 18 h exposure to 1, 2, and 3 µM Zn2+ were similar (8%, 7%, and 12%, respectively) compared with 7% in controls. Cells exposed to 3 µM Zn2+ increased cell populations in G2/M phase (76% versus 68% in controls). Interestingly, exposure to 1 µM Zn2+ resulted in decreased (59%) cells in G2/M. While preliminary, these pilot studies suggest Zn2+ alters cell cycle in BEAS-2B cells, particularly in the G2/M phase. The G2/M checkpoint maintains DNA integrity by enabling initiation of DNA repair or apoptosis. Our findings suggest that the adaptive and apoptotic responses to Zn2+ exposure may be mediated via perturbation of the cell cycle at the G2/M checkpoint. This work was a collaborative summer student project. The st

  12. Episodic Disturbance from Boat Anchoring Is a Major Contributor to, but Does Not Alter the Trajectory of, Long-Term Coral Reef Decline.

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    Graham E Forrester

    Full Text Available Isolating the relative effects of episodic disturbances and chronic stressors on long-term community change is challenging. We assessed the impact of an episodic disturbance associated with human visitation (boat anchoring relative to other drivers of long-term change on coral reefs. A one-time anchoring event at Crab Cove, British Virgin Islands, in 2004 caused rapid losses of coral and reef structural complexity that were equal to the cumulative decline over 23 years observed at an adjacent site. The abundance of small site-attached reef fishes dropped by approximately one quarter after the anchoring event, but this drop was not immediate and only fully apparent two years after the anchoring event. There was no obvious recovery from the impact, and no evidence that this episodic impact accelerated or retarded subsequent declines from other causes. This apparent lack of synergism between the effect of this episodic human impact and other chronic stressors is consistent with the few other long-term studies of episodic impacts, and suggests that action to mitigate anchor damage should yield predictable benefits.

  13. Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity

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    Thiel Cora S

    2012-01-01

    Full Text Available Abstract In our study we aimed to identify rapidly reacting gravity-responsive mechanisms in mammalian cells in order to understand if and how altered gravity is translated into a cellular response. In a combination of experiments using "functional weightlessness" provided by 2D-clinostats and real microgravity provided by several parabolic flight campaigns and compared to in-flight-1g-controls, we identified rapid gravity-responsive reactions inside the cell cycle regulatory machinery of human T lymphocytes. In response to 2D clinorotation, we detected an enhanced expression of p21 Waf1/Cip1 protein within minutes, less cdc25C protein expression and enhanced Ser147-phosphorylation of cyclinB1 after CD3/CD28 stimulation. Additionally, during 2D clinorotation, Tyr-15-phosphorylation occurred later and was shorter than in the 1 g controls. In CD3/CD28-stimulated primary human T cells, mRNA expression of the cell cycle arrest protein p21 increased 4.1-fold after 20s real microgravity in primary CD4+ T cells and 2.9-fold in Jurkat T cells, compared to 1 g in-flight controls after CD3/CD28 stimulation. The histone acetyltransferase (HAT inhibitor curcumin was able to abrogate microgravity-induced p21 mRNA expression, whereas expression was enhanced by a histone deacetylase (HDAC inhibitor. Therefore, we suppose that cell cycle progression in human T lymphocytes requires Earth gravity and that the disturbed expression of cell cycle regulatory proteins could contribute to the breakdown of the human immune system in space.

  14. Evaluation of surface properties and atmospheric disturbances caused by post-dam alterations of land use/land cover

    Science.gov (United States)

    Woldemichael, A. T.; Hossain, F.; Pielke, R., Sr.

    2014-09-01

    This study adopted a differential land-use/land-cover (LULC) analysis to evaluate dam-triggered land-atmosphere interactions for a number of LULC scenarios. Two specific questions were addressed: (1) can dam-triggered LULC heterogeneities modify surface and energy budget, which, in turn, change regional convergence and precipitation patterns? (2) How extensive is the modification in surface moisture and energy budget altered by dam-triggered LULC changes occurring in different climate and terrain features? The Regional Atmospheric Modeling System (RAMS, version 6.0) was set up for two climatologically and topographically contrasting regions: the American River watershed (ARW), located in California, and the Owyhee River watershed (ORW), located in eastern Oregon. For the selected atmospheric river precipitation event of 29 December 1996 to 3 January 1997, simulations of three pre-defined LULC scenarios are performed. The definition of the scenarios are (1) the "control" scenario, representing the contemporary land use, (2) the "pre-dam" scenario, representing the natural landscape before the construction of the dams and (3) the "non-irrigation" scenario, representing the condition where previously irrigated landscape in the control is transformed to the nearby land-use type. Results indicated that the ARW energy and moisture fluxes were more extensively affected by dam-induced changes in LULC than the ORW. Both regions, however, displayed commonalities in the modification of land-atmosphere processes due to LULC changes, with the control-non-irrigation scenario creating more change than the control-pre-dam scenarios. These commonalities were: (1) the combination of a decrease in temperature (up to 0.15 °C) and an increase at dew point (up to 0.25 °C) was observed; (2) there was a larger fraction of energy partitioned to latent heat flux (up to 10 W m-2) that increased the amount of water vapor in the atmosphere and resulted in a larger convective available

  15. Evaluation of surface properties and atmospheric disturbances caused by post-dam alterations of land-use/land-cover

    Science.gov (United States)

    Woldemichael, A. T.; Hossain, F.; Pielke, R., Sr.

    2014-05-01

    This study adopted a differential land-use/land-cover (LULC) analysis to evaluate dam-triggered land-atmosphere interactions for a number of LULC scenarios. Two specific questions were addressed: (1) can dam-triggered LULC heterogeneities modify surface and energy budget which, in turn, change regional convergence and precipitation patterns? and (2) how extensive is the modification in surface moisture and energy budget altered by dam-triggered LULC changes occurring in different climate and terrain features? The Regional Atmospheric Modeling System (RAMS, version 6.0) was set up for two climatologically and topographically contrasting regions: the American River Watershed (ARW) located in California and the Owyhee River Watershed (ORW) located in eastern Oregon. For the selected atmospheric river precipitation event of 29 December 1996 to 3 January 1997, simulations of three pre-defined LULC scenarios are performed. The definition of the scenarios are: (1) the control scenario representing the contemporary land-use, (2) the pre-dam scenario representing the natural landscape before the construction of the dams and (3) the non-irrigation scenario representing the condition where previously irrigated landscape in the control is transformed to the nearby land-use type. Results indicated that the ARW energy and moisture fluxes were more extensively affected by dam-induced changes in LULC than the ORW. Both regions, however, displayed commonalities in the modification of land-atmosphere processes due to LULC changes, with the control-non-irrigation scenario creating more change than the control-pre-dam scenarios. These commonalities were: (1) the combination of a decrease in temperature (up to 0.15 °C) and an increase in dewpoint (up to 0.25 °C) was observed, (2) there was a larger fraction of energy partitioned to latent heat flux (up to 10 W m-2) that increased the amount of water vapor to the atmosphere and resulted in a larger convective available potential

  16. Evaluation of surface properties and atmospheric disturbances caused by post-dam alterations of land-use/land-cover

    Directory of Open Access Journals (Sweden)

    A. T. Woldemichael

    2014-05-01

    Full Text Available This study adopted a differential land-use/land-cover (LULC analysis to evaluate dam-triggered land–atmosphere interactions for a number of LULC scenarios. Two specific questions were addressed: (1 can dam-triggered LULC heterogeneities modify surface and energy budget which, in turn, change regional convergence and precipitation patterns? and (2 how extensive is the modification in surface moisture and energy budget altered by dam-triggered LULC changes occurring in different climate and terrain features? The Regional Atmospheric Modeling System (RAMS, version 6.0 was set up for two climatologically and topographically contrasting regions: the American River Watershed (ARW located in California and the Owyhee River Watershed (ORW located in eastern Oregon. For the selected atmospheric river precipitation event of 29 December 1996 to 3 January 1997, simulations of three pre-defined LULC scenarios are performed. The definition of the scenarios are: (1 the control scenario representing the contemporary land-use, (2 the pre-dam scenario representing the natural landscape before the construction of the dams and (3 the non-irrigation scenario representing the condition where previously irrigated landscape in the control is transformed to the nearby land-use type. Results indicated that the ARW energy and moisture fluxes were more extensively affected by dam-induced changes in LULC than the ORW. Both regions, however, displayed commonalities in the modification of land–atmosphere processes due to LULC changes, with the control–non-irrigation scenario creating more change than the control–pre-dam scenarios. These commonalities were: (1 the combination of a decrease in temperature (up to 0.15 °C and an increase in dewpoint (up to 0.25 °C was observed, (2 there was a larger fraction of energy partitioned to latent heat flux (up to 10 W m−2 that increased the amount of water vapor to the atmosphere and resulted in a larger convective available

  17. The effects of human disturbance on the activity of wild reindeer in different physical condition

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    Terje Skogland

    1988-06-01

    Full Text Available We compared two Norwegian wild reindeer herds, Knutsho in excellent physical condition and Hardangervidda in poor physical condition, before and during disturbance by human hunters in order to test whether physical condition effected foraging strategy under stress. Both herds were being regularly hunted (man had been a natural predator on reindeer since prehistoric time. The well-fed Knutsho animals were ca. 30% larger at the start of the hunting season in late August. Before exposure they foraged less and walked more, i.e. were more selective than the Hardangervidda animals which were in energetically lower condition and foraged significantly more and spent less time moving between habitat patches and less time standing. After exposure to hunters disturbed Knutsho animals aggregated into significantly larger groups than before hunting and stood alert more, while Hardangervidda animals spent the same minimum amount of time foraging but moved significantly more and spent almost no time standing. The frequency of disturbance was not significantly different between the two herds and their speeds of movement after disturbances were similar. The hunter kill success rate was also similar in the two areas. The energetic costs, measured as relative body weight loss during the hunting season, was higher for the initially less well-fed Hardangervidda animals, and higher for both herds compared to that from a less disturbed herd (Forelhogna. We hypothezise that while standing still and alert in aggregated groups is risky, it is still more risky to move, but potentially more rewarding if a better habitat could be found. More well-fed Knutsho animals, which aggregated and stood still, conserved allready stored energy, compatible with a time minimizer risk aversive strategy. The Hardangervidda animals which were in poorer condition increased travelling time to an extent that suggested a risky nutrient miximizer strategy in the phase of stress.Effekter av

  18. Distribution of a community of mammals in relation to roads and other human disturbances in Gabon, central Africa.

    Science.gov (United States)

    Vanthomme, Hadrien; Kolowski, Joseph; Korte, Lisa; Alonso, Alfonso

    2013-04-01

    We present the first community-level study of the associations of both roads and other human disturbances with the distribution of mammals in Gabon (central Africa). Our study site was in an oil concession within a littoral mosaic landscape. We conducted surveys along 199 line transects and installed camera traps on 99 of these transects to document mammal presence and abundance. We used generalized linear mixed-effect models to document associations between variables related to the ecosystem (land cover, topography, and hydrology), roads (coating, width of rights of way, condition, type of vehicle used on the road, traffic level, affiliation of users, and general type of road), and other human disturbances (urbanization, agriculture, hunting, logging, gathering, and industrial activities) and the abundance or presence of 17 species or groups of mammals including elephant (Loxodonta cyclotis), buffalo (Syncerus caffer), sitatunga (Tragelaphus spekei), red river hog (Potamochoerus porcus), smaller ungulates, gorilla (Gorilla gorilla), chimpanzee (Pan troglodytes), side-striped jackal (Canis adustus), carnivores, monkeys, and large rodents. Some types of roads and other human disturbances were negatively associated with the abundance or presence of elephants, buffalos, gorillas, sitatungas, some monkeys, and duikers. The pattern of associations of mammals with roads and other human disturbances was diverse and included positive associations with road presence (red river hog, some monkeys, and duikers), agriculture (sitatunga, small carnivores, and large rodents) and industrial activities (sitatunga, red river hog, red duikers, and side-striped jackal). Our results suggest that the community of mammals we studied was mostly affected by hunting, agriculture, and urbanization, which are facilitated by road presence. We recommend increased regulation of agriculture, hunting, and road building in the area.

  19. Vertebrates respond differently to human disturbance: implications for the use of a focal species approach

    Science.gov (United States)

    Ficetola, Gentile Francesco; Sacchi, Roberto; Scali, Stefano; Gentilli, Augusto; De Bernardi, Fiorenza; Galeotti, Paolo

    2007-01-01

    Focal species are surrogates assuming that all species under consideration respond similarly to the threatening processes. Focusing management only on a small number of species would improve conditions for other species. However, the across-taxa congruency of the response to threatening processes, and the subsequent efficiency of focal species as surrogates, has seldom been tested. In this study, we evaluated the effects of recreational disturbance and wood structure on the communities of terrestrial vertebrates in the wood patches of a large urban park. We measured two effects of recreation: direct disturbance (people presence) and litter disturbance (effect of trampling). We used multiple techniques to assess the distribution of small mammals, birds, reptiles and amphibians in 44 wood patches. Disturbance and wood maturity influenced the distribution of some species and the species richness of amphibians and reptiles; however, the pattern was not consistent across species within classes or among classes. The performance of focal species as a multi species umbrella was poor. Our results suggest that species specific differences in the response to the same source of disturbance can be strong; these differences can hinder the usefulness of focal species as surrogates and as a management tool.

  20. Absolute quantification of somatic DNA alterations in human cancer.

    Science.gov (United States)

    Carter, Scott L; Cibulskis, Kristian; Helman, Elena; McKenna, Aaron; Shen, Hui; Zack, Travis; Laird, Peter W; Onofrio, Robert C; Winckler, Wendy; Weir, Barbara A; Beroukhim, Rameen; Pellman, David; Levine, Douglas A; Lander, Eric S; Meyerson, Matthew; Getz, Gad

    2012-05-01

    We describe a computational method that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. The method, named ABSOLUTE, can detect subclonal heterogeneity and somatic homozygosity, and it can calculate statistical sensitivity for detection of specific aberrations. We used ABSOLUTE to analyze exome sequencing data from 214 ovarian carcinoma tumor-normal pairs. This analysis identified both pervasive subclonal somatic point-mutations and a small subset of predominantly clonal and homozygous mutations, which were overrepresented in the tumor suppressor genes TP53 and NF1 and in a candidate tumor suppressor gene CDK12. We also used ABSOLUTE to infer absolute allelic copy-number profiles from 3,155 diverse cancer specimens, revealing that genome-doubling events are common in human cancer, likely occur in cells that are already aneuploid, and influence pathways of tumor progression (for example, with recessive inactivation of NF1 being less common after genome doubling). ABSOLUTE will facilitate the design of clinical sequencing studies and studies of cancer genome evolution and intra-tumor heterogeneity.

  1. Neuroendocrine alterations in the exercising human: implications for energy homeostasis.

    Science.gov (United States)

    Fuqua, John S; Rogol, Alan D

    2013-07-01

    Complex mechanisms exist in the human to defend against adverse effects of negative energy balance. These include alterations of hormone secretion affecting the growth hormone/insulin-like growth factor system, the adrenal axis, and the reproductive system, particularly in females. Energy deficits are least partially offset by neuroendocrine mechanisms regulating appetite and satiety. The complex feedback mechanisms reporting peripheral fat and energy stores to the central nervous system involve secretion of the peptide hormones leptin and ghrelin, which act centrally on neurons in the arcuate nucleus and anteroventral periventricular area. In addition to appetite regulation, these hormones exert influences on spatially and functionally-related mechanisms regulating reproductive function, such as the kisspeptin-gonadotropin releasing hormone system. Negative energy balance often occurs partially as a result of strenuous and repetitive physical exercise. Exercise stress leads to increased cortisol secretion, but this action is mediated through the induced negative energy balance. In healthy adults with energy deficits, this exercise-induced stress appears to be more important than pure psychological stress in impairing reproductive function. Estrogen deficiency resulting from negative energy balance has important adverse effects on bone density as well as bone microarchitecture, and it may also adversely affect markers of cardiovascular disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Diversity and network structure of invertebrate communities associated to Heliconia species in natural and human disturbed tropical rain forests

    Directory of Open Access Journals (Sweden)

    Julieta Benítez-Malvido

    2014-12-01

    Full Text Available We analyzed the influence of natural and anthropogenic habitat disturbance on the structure of invertebrate communities living on two species of Heliconia herbs. We compared the invertebrate community structure associated to both species growing in natural forest gaps, on road edges for H. latispatha, and in riparian vegetation for H. collinsiana. We assessed the topological structure of individual-based Heliconia–invertebrate networks. Species richness was greater in H. collinsiana inhabiting riparian vegetation but no differences were found in the diversity of invertebrates for any Heliconia species and habitat. Invertebrate abundance was greater in gaps for H. latispatha and in riparian vegetation for H. collinsiana showing a species turnover in human disturbed habitats. The invertebrate community was not randomly assembled but highly nested, revealing a structured pattern for all habitat conditions. Heliconia–invertebrate network properties appear to be maintained in human disturbed habitats, despite differences in species richness, abundance and composition and host number and quality. Our study contributes to the understanding of the structure of ecological interactions in contrasting habitats. Because they provide food and habitat for the associated fauna and several microhabitats for colonization, heliconias could be used as habitat elements for invertebrate conservation in human impacted landscapes.

  3. Retinal Remodeling And Metabolic Alterations in Human AMD

    Directory of Open Access Journals (Sweden)

    Bryan William Jones

    2016-04-01

    Full Text Available Age-related macular degeneration (AMD is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression.The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this paper is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE, for remodeling of the the neural retina.Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP, a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming in progressive retinal degenerations such as retinitis pigmentosa (RP. We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease.Major findings: 1 Evidence of metabolic instability in RPE in dry-AMD.2 Photoreceptors show clear indications of stress prior to cell death.3 Cone opsin processing by the RPE in AMD retinas may be differentially compromised vs. rod opsin.4 Müller cells in AMD exhibit

  4. Disturbing forest disturbances

    Energy Technology Data Exchange (ETDEWEB)

    Volney, W.J.A.; Hirsch, K.G. [Natural Resources Canada, Canadian Forest Service, Northern Forestry Centre, Edmonton, AB (Canada)

    2005-10-01

    This paper described the role that disturbances play in maintaining the ecological integrity of Canadian boreal forests. Potential adaptation options to address the challenges that these disturbances present were also examined. Many forest ecosystems need fire for regeneration, while other forests rely on a cool, wet disintegration process driven by insects and commensal fungi feeding on trees to effect renewal. While there are characteristic natural, temporal and spatial patterns to these disturbances, recent work has demonstrated that the disturbances are being perturbed by climatic change that has been compounded by anthropogenic disturbances in forests. Fire influences species composition and age structure, regulates forest insects and diseases, affects nutrient cycling and energy fluxes, and maintains the productivity of different habitats. Longer fire seasons as a result of climatic change will lead to higher intensity fires that may more easily evade initial attacks and become problematic. Fire regimes elevated beyond the range of natural variation will have a dramatic effect on the regional distribution and functioning of forest ecosystems and pose a threat to the safety and prosperity of people. While it was acknowledged that if insect outbreaks were to be controlled on the entire forest estate, the productivity represented by dead wood would be lost, it was suggested that insects such as the forest tent caterpillar and the spruce bud worm may also pose a greater threat as the climate gets warmer and drier. Together with fungal associates, saproxylic arthropods are active in nutrient cycling and ultimately determine the fertility of forest sites. It was suggested that the production of an age class structure and forest mosaic would render the forest landscape less vulnerable to the more negative aspects of climate change on vegetation response. It was concluded that novel management design paradigms are needed to successfully reduce the risk from threats

  5. Human Auditory Communication Disturbances Due To Road Traffic Noise Pollution in Calabar City, Nigeria

    Directory of Open Access Journals (Sweden)

    E. O. Obisung

    2016-10-01

    Full Text Available Study on auditory communication disturbances due to road transportation noise in Calabar Urban City, Nigeria was carried out. Both subjective (psycho-social and objective (acoustical measurements were made for a period of twelve months. Questionnaire/interview schedules containing pertinent questions were administered randomly to 500 respondents of age 15 year and above, who were also with a good level of literacy skills (reading writing and leaving in houses sited along or parallel to busy road, with heavy traffic volume for at least three (3 years. The questionnaires provided the psycho-social responses of respondents used in this study, their reactions to road traffic noise effect on communication activities (listening to radio, listening and watching television, verbal communication between individuals, speech communication and telephone/GSM communication. Acoustical measurements were made at the facades of respondents' houses facing the road using precision digital sound level meter, Bruel and Kjaer (B & K type 732 following ISO standards 1996. The meter read the road traffic noise levels at measurement sites (facades of respondents' houses. From the results obtained in this study residents of Calabar City suffer serious communication interferences as a result of excessive road traffic noise levels. The noise indices used for this study were LAeq and Ldn. Noise levels obtained were over 93 dB(A (daytime and 60 dB(A, (nighttime for LAeq and 80 dB(A for Ldn. These far exceeded the recommended theoretical values of 45-55 and 70 dB(A, for LAeqand Ldn respectively. A-weighted sound pressure level (SPLS range between 87.0 and 100.0 dB(A. In this study it was also observed that over 98% of the respondents reported their television watching/radio listening disturbed, 99% recorded telephone/GSM disturbed, and 98% reported face-to-face verbal conversation disturbed, and 98% reported speech communication disturbed. The background noise levels (BNLs of

  6. Altitudinal ranging of black-crested gibbons at Mt. Wuliang, Yunnan: effects of food distribution, temperature and human disturbance.

    Science.gov (United States)

    Fan, Peng-Fei; Jiang, Xue-Long

    2010-01-01

    We studied the altitudinal ranging of one habituated group of black-crested gibbons (Nomascus concolor) at Dazhaizi, Mt. Wuliang, Yunnan, China, between March 2005 and April 2006. The group ranged from 1,900 to 2,680 m above sea level. Food distribution was the driving force behind the altitudinal ranging patterns of the study group. They spent 83.2% of their time ranging between 2,100 and 2,400 m, where 75.8% of important food patches occurred. They avoided using the area above 2,500 m despite a lack of human disturbance there, apparently because there were few food resources. Temperature had a limited effect on seasonal altitudinal ranging but probably explained the diel altitudinal ranging of the group, which tended to use the lower zone in the cold morning and the higher zone in the warm afternoon. Grazing goats, the main disturbance, were limited to below 2,100 m, which was defined as the high-disturbance area (HDA). Gibbons spent less time in the HDA and, when ranging there, spent more time feeding and travelling and less time resting and singing. Human activities directly influenced gibbon behaviour, might cause forest degradation and create dispersal barriers between populations.

  7. Creation of Alternate Stable States in Tropical Dry Forests as a Consequence of Human Disturbance

    Science.gov (United States)

    Van Bloem, S. J.; Whitmire, S. L.; Thaxton, J.

    2015-12-01

    Anthropogenic disturbances in Caribbean subtropical dry forests of the Caribbean lead to either novel species assemblages in post-disturbance forest, or stable degraded grassland states. Among these disturbances are fire and clearing. Short-term responses to both disturbances include sharp increases in nutrient fluxes, shifts in soil moisture availability, and the spread of invasive grass species if seed sources are nearby. In Guánica Forest, Puerto Rico, our studies in sites that were frequently burned and a chronosequence of once-burned sites beginning 30 years ago showed that fire is associated with invasion by exotic grass species and that once invaded, grass dominated sites do not revert to forest. After 30 years, single burn sites were still ≥65% lower in basal area and species richness than native forest. Frequently burned sites had 60-75% lower soil N, 50-65% lower S, and 56-68% lower C, as well as elevated Fe and pH. A single burn in a previously unburned forest elevated NO3 flux ~6-fold for at least the next year. Once dominated by grass, tree seed rain is extremely low (7 seeds/m2/y). Low dispersal rates combined with low germination rates makes forest regeneration unlikely. In contrast, sites that cleared or plowed without grass invasion regain structural characteristics of native forests in approximately 40 years. However, these sites are typically dominated by Leucaena leucocephala, a naturalized tree introduced to the island in the 1700s. The proportion of native-species saplings in the understory of Leucaena-dominated forests increased by 0.85%/yr in stands >35 years old until reaching ~95% in 76 yr old stands, suggesting that Leucaena facilitated the reestablishment of native species. We conclude that when anthropogenic disturbance creates grass-dominated sites, these areas will remain stable degraded states. Leucaena can serve as an alternate pathway to forest restoration, facilitating the return of forest cover with a novel combination of

  8. Effect of human disturbance on the structure and regeneration of forests in the Nevado de Toluca National Park, Mexico

    Institute of Scientific and Technical Information of China (English)

    Angel Rolando Endara Agramont; Sergio Franco Maass; Gabino Nava Bemal; Juan Ignacio Valdez Hemández; Todd S.Fredericksen

    2012-01-01

    Sample plots were established in the principal forest types in the the Nevado de Toluca National Park,Mexico including those dominated by Pinus hartwegii,Abies religiosa,Quercus laurina and Alnus jorullensis.The vertical structure was defined by three strata in the coniferous forests and two strata in the broadleaved forests.Timber harvesting in Abies religiosa and Quercus laurina forests and fires generated by humans in Pinus hartwegii forests impeded the recruitment of saplings.Mature trees were also heavily impacted by logging in Pinus hartwegii forests.On the contrary,Alnusjorullensis forests were increasing due to the disturbance of Pinus and Quercus forests,as well abandoned crop lands within the park.A combination of logging,uncontrolled fire,and grazing appears to be compromising the recruitment of important tree species in this national park.These factors,together with human settlements,have also increased the proportion of early successional species.Changes in forest structure from human disturbance indicate a need to control these activities if conservation goals are not to be compromised.

  9. Late Mesolithic and early Neolithic forest disturbance: a high resolution palaeoecological test of human impact hypotheses

    Science.gov (United States)

    Innes, James B.; Blackford, Jeffrey J.; Rowley-Conwy, Peter A.

    2013-10-01

    The transition in north-west Europe from the hunter-gatherer societies of the Late Mesolithic to the pioneer farming societies of the early Neolithic is not well understood, either culturally or palaeoecologically. In Britain the final transition was rapid but it is unclear whether novel Neolithic attributes were introduced by immigrants who supplanted the native hunter-gatherers, or whether the latest Mesolithic foragers gradually adopted elements of the Neolithic economic package. In this study, relatively coarse- (10 mm interval) and fine-resolution (2 mm), multi-proxy palaeoecological data including pollen, charcoal and NPPs including fungi, have been used to investigate two phases of vegetation disturbance of (a) distinctly Late Mesolithic and (b) early Neolithic age, at an upland site in northern England in a region with both a Neolithic and a Late Mesolithic archaeological presence. We identify and define the palaeoecological characteristics of these two disturbance phases, about a millennium apart, in order to investigate whether differing land-use techniques can be identified and categorised as of either foraging or early farming cultures. The Late Mesolithic phase is defined by the repetitive application of fire to the woodland to encourage a mosaic of productive vegetation regeneration patches, consistent with the promotion of Corylus and to aid hunting. In this phase, weed species including Plantago lanceolata, Rumex and Chenopodiaceae are frequent, taxa which are normally associated with the first farmers. The early Neolithic phase, including an Ulmus decline, has characteristics consistent with 'forest farming', possibly mainly for domestic livestock, with an inferred succession of tree girdling, fire-prepared cultivation, and coppice-woodland management. Such fine-resolution, potentially diagnostic land-use signatures may in future be used to recognise the cultural complexion of otherwise enigmatic woodland disturbance phases during the centuries of

  10. Simulation of Local Blood Flow in Human Brain under Altered Gravity

    Science.gov (United States)

    Kim, Chang Sung; Kiris, Cetin; Kwak, Dochan

    2003-01-01

    In addition to the altered gravitational forces, specific shapes and connections of arteries in the brain vary in the human population (Cebral et al., 2000; Ferrandez et al., 2002). Considering the geometric variations, pulsatile unsteadiness, and moving walls, computational approach in analyzing altered blood circulation will offer an economical alternative to experiments. This paper presents a computational approach for modeling the local blood flow through the human brain under altered gravity. This computational approach has been verified through steady and unsteady experimental measurements and then applied to the unsteady blood flows through a carotid bifurcation model and an idealized Circle of Willis (COW) configuration under altered gravity conditions.

  11. Sleep Disturbances

    Science.gov (United States)

    ... PD / Coping with Symptoms & Side Effects / Sleep Disturbances Sleep Disturbances Many people with Parkinson’s disease (PD) have ... stay awake during the day. Tips for Better Sleep People with PD — and their care partners too — ...

  12. Alterations of the human gut microbiome in multiple sclerosis

    Science.gov (United States)

    Jangi, Sushrut; Gandhi, Roopali; Cox, Laura M.; Li, Ning; von Glehn, Felipe; Yan, Raymond; Patel, Bonny; Mazzola, Maria Antonietta; Liu, Shirong; Glanz, Bonnie L.; Cook, Sandra; Tankou, Stephanie; Stuart, Fiona; Melo, Kirsy; Nejad, Parham; Smith, Kathleen; Topçuolu, Begüm D.; Holden, James; Kivisäkk, Pia; Chitnis, Tanuja; De Jager, Philip L.; Quintana, Francisco J.; Gerber, Georg K.; Bry, Lynn; Weiner, Howard L.

    2016-01-01

    The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=60) and healthy controls (n=43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis. PMID:27352007

  13. Insulin resistance alters islet morphology in nondiabetic humans

    DEFF Research Database (Denmark)

    Mezza, Teresa; Muscogiuri, Giovanna; Sorice, Gian Pio

    2014-01-01

    Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also affects...... pancreatic β-cells. To directly examine the alterations that occur in islet morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy from nondiabetic subjects who were insulin-resistant or insulin-sensitive. We also compared...... insulin sensitivity, insulin secretion, and incretin levels between the two groups. We report an increased islet size and an elevated number of β- and α-cells that resulted in an altered β-cell-to-α-cell area in the insulin- resistant group. Our data in this series of studies suggest that neogenesis from...

  14. Clinical implications of epigenetic alterations in human thoracic malignancies: epigenetic alterations in lung cancer.

    Science.gov (United States)

    Shinjo, Keiko; Kondo, Yutaka

    2012-01-01

    Besides known genetic aberrations, epigenetic alterations have emerged as common hallmarks of many cancer types, including lung cancer. Epigenetics is a process involved in gene regulation, mediated via DNA methylation, histone modification, chromatin remodeling, and functional noncoding RNAs, which influences the accessibility of the underlying DNA to transcriptional regulatory factors that activate or repress expression. Studies have shown that epigenetic dysregulation is associated with multiple steps during carcinogenesis. Since epigenetic therapy is now in clinical use in hematopoietic diseases and undergoing trials for lung cancer, a better understanding of epigenetic abnormalities is desired. Recent technologies for high-throughput genome-wide analyses for epigenetic modifications are promising and potent tools for understanding the global dysregulation of cancer epigenetics. In this chapter, studies of epigenetic abnormality and its clinical implication in lung cancers are discussed.

  15. Absolute quantification of somatic DNA alterations in human cancer

    OpenAIRE

    Carter, Scott L.; Cibulskis, Kristian; Helman, Elena; McKenna, Aaron; Shen, Hui; Zack, Travis; Laird, Peter W.; Onofrio, Robert C.; Winckler, Wendy; Weir, Barbara A; Beroukhim, Rameen; Pellman, David; Levine, Douglas A.; Lander, Eric S.; Meyerson, Matthew

    2012-01-01

    We developed a computational method (ABSOLUTE) that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. ABSOLUTE can detect subclonal heterogeneity, somatic homozygosity, and calculate statistical sensitivity to detect specific aberrations. We used ABSOLUTE to analyze ovarian cancer data and identified pervasive subclonal somatic point mutations. In contrast, mutations occurring in key tumor suppressor genes, TP53 and NF1 were predominantly clonal ...

  16. Absolute quantification of somatic DNA alterations in human cancer

    OpenAIRE

    Carter, Scott L.; Cibulskis, Kristian; Helman, Elena; McKenna, Aaron; Shen, Hui; Zack, Travis; Laird, Peter W.; Onofrio, Robert C.; Winckler, Wendy; Weir, Barbara A; Beroukhim, Rameen; Pellman, David; Levine, Douglas A.; Lander, Eric S.; Meyerson, Matthew

    2015-01-01

    We developed a computational method (ABSOLUTE) that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. ABSOLUTE can detect subclonal heterogeneity, somatic homozygosity, and calculate statistical sensitivity to detect specific aberrations. We used ABSOLUTE to analyze ovarian cancer data and identified pervasive subclonal somatic point mutations. In contrast, mutations occurring in key tumor suppressor genes, TP53 and NF1 were predominantly clonal ...

  17. Modeling Human Perception of Orientation in Altered Gravity

    Directory of Open Access Journals (Sweden)

    Torin K. Clark

    2015-05-01

    Full Text Available Altered gravity environments, such as those experienced by astronauts, impact spatial orientation perception and can lead to spatial disorientation and sensorimotor impairment. To more fully understand and quantify the impact of altered gravity on orientation perception, several mathematical models have been proposed. The utricular shear, tangent, and the idiotropic vector models aim to predict static perception of tilt in hyper-gravity. Predictions from these prior models are compared to the available data, but are found to systematically err from the perceptions experimentally observed. Alternatively, we propose a modified utricular shear model for static tilt perception in hyper-gravity. Previous dynamic models of vestibular function and orientation perception are limited to 1 G. Specifically, they fail to predict the characteristic overestimation of roll tilt observed in hyper-gravity environments. To address this, we have proposed a modification to a previous observer-type canal otolith interaction model based upon the hypothesis that the central nervous system treats otolith stimulation in the utricular plane differently than stimulation out of the utricular plane. Here we evaluate our modified utricular shear and modified observer models in four altered gravity motion paradigms: a static roll tilt in hyper-gravity, b static pitch tilt in hyper-gravity, c static roll tilt in hypo-gravity, and d static pitch tilt in hypo-gravity. The modified models match available data in each of the conditions considered. Our static modified utricular shear model and dynamic modified observer model may be used to help quantitatively predict astronaut perception of orientation in altered gravity environments.

  18. Persistent organic pollutants alter DNA methylation during human adipocyte differentiation

    NARCIS (Netherlands)

    Dungen, van den Myrthe; Murk, Tinka; Steegenga, Wilma; Gils-Kok, van Dieuwertje

    2016-01-01

    Genome-wide DNA methylation profiling was performed in human mesenchymal stem cells (hMSCs) differentiated into adipocytes (day 10) while being continuously exposed to either one of three different persistent organic pollutants (POPs), namely TCDD, PFOS, and TBT. The Illumina Infinium 450K Human DNA

  19. Altered A-to-I RNA Editing in Human Embryogenesis

    Science.gov (United States)

    Mandel, Rachel; Ziskind, Anna; Nahor, Irit; Safran, Michal; Osenberg, Sivan; Sherf, Ofra; Rechavi, Gideon; Itskovitz-Eldor, Joseph

    2012-01-01

    Post-transcriptional events play an important role in human development. The question arises as to whether Adenosine to Inosine RNA editing, catalyzed by the ADAR (Adenosine Deaminase acting on RNA) enzymes, differs in human embryogenesis and in adulthood. We tested the editing of various target genes in coding (FLNA, BLCAP, CYFIP2) and non-coding sequences at their Alu elements (BRCA1, CARD11, RBBP9, MDM4, FNACC), as well as the transcriptional levels of the ADAR1 enzymes. This analysis was performed on five fetal and adult human tissues: brain, heart, liver, kidney, and spleen, as well as on human embryonic stem cells (hESCs), which represent the blastocyst stage in early human development. Our results show substantially greater editing activity for most adult tissue samples relative to fetal ones, in six of the eight genes tested. To test the effect of reduced A-to-I RNA editing activity in early human development we used human embryonic stem cells (hESCs) as a model and tried to generate hESC clones that overexpress the ADAR1–p110 isoform. We were unable to achieve overexpression of ADAR1–p110 by either transfection or lentiviral infection, though we easily generated hESC clones that expressed the GFP transgene and overexpressed ADAR1-p110 in 293T cells and in primary human foreskin fibroblast (HFF) cells. Moreover, in contrast to the expected overexpression of ADAR1-p110 protein following its introduction into hESCs, the expression levels of this protein decreased dramatically 24–48 hr post infection. Similar results were obtained when we tried to overexpress ADAR1-p110 in pluripotent embryonal carcinoma cells. This suggests that ADAR1 protein is substantially regulated in undifferentiated pluripotent hESCs. Overall, our data suggest that A-to-I RNA editing plays a critical role during early human development. PMID:22859999

  20. Altered A-to-I RNA editing in human embryogenesis.

    Directory of Open Access Journals (Sweden)

    Ronit Shtrichman

    Full Text Available Post-transcriptional events play an important role in human development. The question arises as to whether Adenosine to Inosine RNA editing, catalyzed by the ADAR (Adenosine Deaminase acting on RNA enzymes, differs in human embryogenesis and in adulthood. We tested the editing of various target genes in coding (FLNA, BLCAP, CYFIP2 and non-coding sequences at their Alu elements (BRCA1, CARD11, RBBP9, MDM4, FNACC, as well as the transcriptional levels of the ADAR1 enzymes. This analysis was performed on five fetal and adult human tissues: brain, heart, liver, kidney, and spleen, as well as on human embryonic stem cells (hESCs, which represent the blastocyst stage in early human development. Our results show substantially greater editing activity for most adult tissue samples relative to fetal ones, in six of the eight genes tested. To test the effect of reduced A-to-I RNA editing activity in early human development we used human embryonic stem cells (hESCs as a model and tried to generate hESC clones that overexpress the ADAR1-p110 isoform. We were unable to achieve overexpression of ADAR1-p110 by either transfection or lentiviral infection, though we easily generated hESC clones that expressed the GFP transgene and overexpressed ADAR1-p110 in 293T cells and in primary human foreskin fibroblast (HFF cells. Moreover, in contrast to the expected overexpression of ADAR1-p110 protein following its introduction into hESCs, the expression levels of this protein decreased dramatically 24-48 hr post infection. Similar results were obtained when we tried to overexpress ADAR1-p110 in pluripotent embryonal carcinoma cells. This suggests that ADAR1 protein is substantially regulated in undifferentiated pluripotent hESCs. Overall, our data suggest that A-to-I RNA editing plays a critical role during early human development.

  1. Evolution of Hydrological Drought in Human Disturbed Areas: A Case Study in the Laohahe Catchment, Northern China

    Directory of Open Access Journals (Sweden)

    Yi Liu

    2016-01-01

    Full Text Available A case study on the evolution of hydrological drought in nonstationary environments is conducted over the Laohahe catchment in northern China. Using hydrometeorological observations during 1964–2009, meteorological and hydrological droughts are firstly analyzed with the threshold level method. Then, a comprehensive analysis on the changes within the catchment is conducted on the basis of hydrological variables and socioeconomic indices, and the whole period is divided into two parts: the undisturbed period (1964–1979 and the disturbed period (1980–2009. A separating framework is further introduced to distinguish droughts induced by different causes, that is, the naturalized drought and human-induced drought. Results showed that human activities are more inclined to play a negative role in aggravating droughts. Drought duration and deficit volume in naturalized conditions are amplified two to four times and three to eight times, respectively, when human activities are involved. For the two dry decades 1980s and 2000s, human activities have caused several consecutive drought events with rather long durations (up to 29 months. These results reflect the considerable impacts of human activities on hydrological drought, which could provide some theoretical support for local drought mitigation and water resources management.

  2. Alcohol induced alterations to the human fecal VOC metabolome.

    Directory of Open Access Journals (Sweden)

    Robin D Couch

    Full Text Available Studies have shown that excessive alcohol consumption impacts the intestinal microbiota composition, causing disruption of homeostasis (dysbiosis. However, this observed change is not indicative of the dysbiotic intestinal microbiota function that could result in the production of injurious and toxic products. Thus, knowledge of the effects of alcohol on the intestinal microbiota function and their metabolites is warranted, in order to better understand the role of the intestinal microbiota in alcohol associated organ failure. Here, we report the results of a differential metabolomic analysis comparing volatile organic compounds (VOC detected in the stool of alcoholics and non-alcoholic healthy controls. We performed the analysis with fecal samples collected after passage as well as with samples collected directly from the sigmoid lumen. Regardless of the approach to fecal collection, we found a stool VOC metabolomic signature in alcoholics that is different from healthy controls. The most notable metabolite alterations in the alcoholic samples include: (1 an elevation in the oxidative stress biomarker tetradecane; (2 a decrease in five fatty alcohols with anti-oxidant property; (3 a decrease in the short chain fatty acids propionate and isobutyrate, important in maintaining intestinal epithelial cell health and barrier integrity; (4 a decrease in alcohol consumption natural suppressant caryophyllene; (5 a decrease in natural product and hepatic steatosis attenuator camphene; and (6 decreased dimethyl disulfide and dimethyl trisulfide, microbial products of decomposition. Our results showed that intestinal microbiota function is altered in alcoholics which might promote alcohol associated pathologies.

  3. Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer.

    Directory of Open Access Journals (Sweden)

    Shinya Akatsuka

    Full Text Available Iron overload has been associated with carcinogenesis in humans. Intraperitoneal administration of ferric nitrilotriacetate initiates a Fenton reaction in renal proximal tubules of rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC after repeated treatments. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of this oxidative stress-induced rat RCCs. The results revealed extensive large-scale genomic alterations with a preference for deletions. Deletions and amplifications were numerous and sometimes fragmented, demonstrating that a Fenton reaction is a cause of such genomic alterations in vivo. Frequency plotting indicated that two of the most commonly altered loci corresponded to a Cdkn2a/2b deletion and a Met amplification. Tumor sizes were proportionally associated with Met expression and/or amplification, and clustering analysis confirmed our results. Furthermore, we developed a procedure to compare whole genomic patterns of the copy number alterations among different species based on chromosomal syntenic relationship. Patterns of the rat RCCs showed the strongest similarity to the human RCCs among five types of human cancers, followed by human malignant mesothelioma, an iron overload-associated cancer. Therefore, an iron-dependent Fenton chemical reaction causes large-scale genomic alterations during carcinogenesis, which may result in distinct genomic profiles. Based on the characteristics of extensive genome alterations in human cancer, our results suggest that this chemical reaction may play a major role during human carcinogenesis.

  4. Acute encephalopathy with concurrent respiratory and metabolic disturbances in first known parenteral human administration of flunixin meglumine and acepromazine maleate.

    Science.gov (United States)

    Kamali, Michael F; Wilson, Anwar C; Acquisto, Nicole M; Spillane, Linda; Schneider, Sandra M

    2013-08-01

    Flunexin is a nonsteroidal anti-inflammatory drug approved for veterinary use in horses and cattle. Acepromazine is a phenothiazine derivative used in horses, dogs, and cats. Human exposure to these substances is rare. We report a case of a human injection of two equine medications, flunixin and acepromazine, which resulted in altered mental status, respiratory alkalosis, gastrointestinal bleeding, and elevation of liver transaminases in a 43-year-old woman who worked as a horse trainer. The patient intentionally self-injected these medications and subsequently presented to the Emergency Department with altered mental status and lethargy. The patient required hospitalization for metabolic abnormalities, including respiratory alkalosis, and suffered a gastrointestinal bleed requiring blood transfusion. The patient ultimately recovered with supportive measures. We believe this to be the first case of concomitant injection of flunixin and acepromazine in a human. This report explains a case of parenteral administration of two equine medications and the subsequent complications in a patient that presented to the Emergency Department. Human exposure to veterinary medications cannot be predicted by their effect in animals due to variations in absorption, distribution, and metabolism. Physicians should be aware that individuals who work with animals may have access to large quantities of veterinary medicine. This case also exemplifies the challenges that Emergency Physicians face on a daily basis, and generates additional consideration for overdoses and intoxications from medications that are not considered commonplace in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Flight initiation distances of nesting Piping Plovers (Charadrius melodus in response to human disturbance

    Directory of Open Access Journals (Sweden)

    Joel G. Jorgensen

    2016-06-01

    Full Text Available Birds frequently interact with people when they occur in coupled human-ecological or anthropogenic environments, which makes the protection of legally protected species a challenge. Flight initiation distances (FIDs are often used to inform development of appropriate buffer distances required for human exclusion zones used to protect birds nesting in anthropogenic landscapes. Piping Plovers (Charadrius melodus are protected by the Endangered Species Act in the United States and often nest in areas used by humans. Studies evaluating Piping Plover FIDs are limited and implementation of exclusion zones has been inconsistent across the species' range. We measured Piping Plover response and FIDs to naturally occurring stimuli on public beaches at Lake McConaughy, Nebraska, USA. Piping Plover FIDs differed most by stimulus class (vehicle, human, dog, human with dog, Julian day, and hour of day. Piping Plover FIDs were greatest for dog and human with dog compared to humans and vehicles. For all types of stimuli, Piping Plover FIDs decreased over time during the nesting season and increased slightly during each day. In the majority of instances in which Piping Plovers left their nests, return times to the nest were relatively short (less than three minutes. These results suggest Piping Plovers become habituated to the presence of human-related stimuli over the course of a nesting season, but other explanations such as parental investment and risk allocation cannot be excluded. Additional research and improved guidance regarding the implementation of exclusion zones is needed so managers can implement effective protection programs in anthropogenic landscapes.

  6. Human growth hormone alters carbohydrate storage in blood and ...

    African Journals Online (AJOL)

    MJP

    2015-06-02

    Jun 2, 2015 ... ... which permits unrestricted use, distribution, and reproduction in any medium, provided the ... of granivorous species, such as the chicken ... dominant in carnivorous avian species.[1] The ... Studies in humans and animal models show ..... rabbits over expressing growth hormone develop acromegaly and.

  7. Concepts and Challenges in Disturbance Hydrology

    Science.gov (United States)

    Ebel, B. A.; Mirus, B. B.

    2016-12-01

    Landscape disturbances are increasing, often promoted and enhanced by climate shifts and human activities. Insect infestations, wildfires, earthquakes, urban development, forest harvest, mineral and petroleum resource extraction, and hurricanes are common landscape disturbances that can have profound hydrologic consequences. These cause relatively abrupt changes in the landscape, which alter local processes on plots and hillslopes in addition to coarser-scale processes across watersheds through cross-scale interactions. Shifts in soil properties and cover of vegetation and leaf litter change the water storage or buffering capacity as well as the hydrologic functional connectivity across multiple scales. These changes increase the risk of catastrophic flooding, erosion, and mass movements that degrade water resources, ecosystem services, and protection from hydrologically driven natural hazards. Although it is imperative that we understand the hydrologic effects of these disturbances, several major barriers exist. Four challenges are: (i) overlapping disturbances in space and time with unknown recovery trajectories, (ii) a paucity of long-term recovery records (>5 years duration), (iii) inefficacy of traditional modeling and parameterization approaches, and (iv) lack of pre-disturbance characterization. Examples of these challenges will be presented along with proposed opportunities for improved mechanistic understanding of processes and thresholds in disturbance hydrology.

  8. Paracetamol-induced spindle disturbances in V79 cells with and without expression of human CYP1A2

    DEFF Research Database (Denmark)

    Jensen, K G; Poulsen, H E; Doehmer, J

    1996-01-01

    Spindle disturbing effects in terms of c-mitosis and cytotoxicity of paracetamol were investigated in two Chinese hamster V79 cell lines, one of which (V79MZh1A2) was transfected with human CYP1A2. This enzyme catalyses the oxidative formation of the reactive paracetamol metabolite, NAPQI, believed...... to initiate hepatoxicity by covalent binding to proteins after overdose. In the native V79 cell line paracetamol increased c-mitosis frequency in a concentration dependent manner from 8.7 + or - 3.5% (control) to 66 + or - 18% at 20 mM. A significant increase to 13.3 + or - 3.5% was first seen at 2.5 m......M in the native cell line (Pparacetamol. At 5 mM paracetamol the c-mitosis frequency was 14.4 + or - 5.0% and 19.0 + or - 3...

  9. Changes in cognitive state alter human functional brain networks

    Directory of Open Access Journals (Sweden)

    Malaak Nasser Moussa

    2011-08-01

    Full Text Available The study of the brain as a whole system can be accomplished using network theory principles. Research has shown that human functional brain networks during a resting state exhibit small-world properties and high degree nodes, or hubs, localized to brain areas consistent with the default mode network (DMN. However, the study of brain networks across different tasks and or cognitive states has been inconclusive. Research in this field is important because the underpinnings of behavioral output are inherently dependent on whether or not brain networks are dynamic. This is the first comprehensive study to evaluate multiple network metrics at a voxel-wise resolution in the human brain at both the whole brain and regional level under various conditions: resting state, visual stimulation, and multisensory (auditory and visual stimulation. Our results show that despite global network stability, functional brain networks exhibit considerable task-induced changes in connectivity, efficiency, and community structure at the regional level.

  10. Human recreation alters behaviour profiles of non-breeding birds on open-coast sandy shores

    Science.gov (United States)

    Schlacher, Thomas A.; Nielsen, Tara; Weston, Michael A.

    2013-02-01

    Sandy beaches are primarily valued for their amenity and property values rather than for their ecological functions and properties. Some human usage of beaches potentially conflicts with the conservation and management of wildlife, such as beach-dwelling birds, on sandy shorelines. Because responses by birds to environmental change, including disturbance by humans, often involve behaviours that carry fitness costs, we quantify behaviour profiles of birds in relation to human occurrence along 200 km of sandy shoreline in Eastern Australia, including the large conservation area of Fraser Island. Disturbance to birds on these shores was considerable: 1) birds encountered motorized vehicles (cars, trucks, buses etc.) during 80% of focal bird observation bouts, 2) birds were flushed in over half (up to 86% in individual species) of all bouts, and 3) individuals spent, on average, one-third of their time on disturbance-related behaviours; this was particularly prevalent for Crested Terns (Thalasseus bergii) which were alert 42% of the time and spent 12% of their time escaping from human stimuli. Overall, this study demonstrated that motorized traffic is the prime agent of disturbance to birds on these beaches, resulting in frequent and time-consuming escape behaviours. These findings also emphasize that management of vehicle-based recreation on beaches needs to be re-aligned to meet conservation requirements in addition to providing leisure opportunities in National Parks and beyond; we identify some salient issue for this development: a) encouragement of social norms that promote environmentally benign beach use not involving motor vehicles, b) creation of spatial refuges for beach wildlife from traffic and other non-compatible uses, and c) investment in developing complementary management actions such as effective set-back distances.

  11. Somatic retrotransposition alters the genetic landscape of the human brain

    OpenAIRE

    Baillie, J. Kenneth; Barnett, Mark W.; Upton, Kyle R; Gerhardt, Daniel J.; Richmond, Todd A.; De Sapio, Fioravante; Brennan, Paul; Rizzu, Patrizia; Smith, Sarah; Fell, Mark; Talbot, Richard T; Gustincich, Stefano; Freeman, Thomas C.; Mattick, John S.; Hume, David A

    2011-01-01

    Retrotransposons are mobile genetic elements that employ a germ line “copy-and-paste” mechanism to spread throughout metazoan genomes 1 . At least 50% of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease 2-3 . Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells 4-5 , excluding early embryo development and some malignancies 6-7 . Recent reports of L1 expressio...

  12. Functional diversity, succession, and human-mediated disturbances in raised bog vegetation.

    Science.gov (United States)

    Dyderski, Marcin K; Czapiewska, Natalia; Zajdler, Mateusz; Tyborski, Jarosław; Jagodziński, Andrzej M

    2016-08-15

    Raised and transitional bogs are one of the most threatened types of ecosystem, due to high specialisation of biota, associated with adaptations to severe environmental conditions. The aim of the study was to characterize the relationships between functional diversity (reflecting ecosystem-shaping processes) of raised bog plant communities and successional gradients (expressed as tree dimensions) and to show how impacts of former clear cuts may alter these relationships in two raised bogs in 'Bory Tucholskie' National Park (N Poland). Herbaceous layers of the plant communities were examined by floristic relevés (25m(2)) on systematically established transects. We also assessed patterns of tree ring widths. There were no relationships between vegetation functional diversity components and successional progress: only functional dispersion was negatively, but weakly, correlated with median DBH. Lack of these relationships may be connected with lack of prevalence of habitat filtering and low level of competition over all the successional phases. Former clear cuts, indicated by peaks of tree ring width, influenced the growth of trees in the bogs studied. In the bog with more intensive clear cuts we found more species with higher trophic requirements, which may indicate nutrient influx. However, we did not observe differences in vegetation patterns, functional traits or functional diversity indices between the two bogs studied. We also did not find an influence of clear cut intensity on relationships between functional diversity indices and successional progress. Thus, we found that alteration of the ecosystems studied by neighbourhood clear cuts did not affect the bogs strongly, as the vegetation was resilient to these impacts. Knowledge of vegetation resilience after clear cuts may be crucial for conservation planning in raised bog ecosystems. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Altered B cell receptor signaling in human systemic lupus erythematosus

    Science.gov (United States)

    Jenks, Scott A.; Sanz, Iñaki

    2009-01-01

    Regulation of B cell receptor signaling is essential for the development of specific immunity while retaining tolerance to self. Systemic lupus erythematosus (SLE) is characterized by a loss of B cell tolerance and the production of anti-self antibodies. Accompanying this break down in tolerance are alterations in B cell receptor signal transduction including elevated induced calcium responses and increased protein phosphorylation. Specific pathways that negatively regulate B cell signaling have been shown to be impaired in some SLE patients. These patients have reduced levels of the kinase Lyn in lipid raft microdomains and this reduction is inversely correlated with increased CD45 in lipid rafts. Function and expression of the inhibitory immunoglobulin receptor FcγRIIB is also reduced in Lupus IgM- CD27+ memory cells. Because the relative contribution of different memory and transitional B cell subsets can be abnormal in SLE patients, we believe studies targeted to well defined B cell subsets will be necessary to further our understanding of signaling abnormalities in SLE. Intracellular flow cytometric analysis of signaling is a useful approach to accomplish this goal. PMID:18723129

  14. Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration.

    Science.gov (United States)

    Freeman, Willard M; Vanguilder, Heather D; Guidone, Elizabeth; Krystal, John H; Grant, Kathleen A; Vrana, Kent E

    2011-08-01

    Objective diagnostics of excessive alcohol use are valuable tools in the identification and monitoring of subjects with alcohol use disorders. A number of potential biomarkers of alcohol intake have been proposed, but none have reached widespread clinical usage, often due to limited diagnostic sensitivity and specificity. In order to identify novel potential biomarkers, we performed proteomic biomarker target discovery in plasma samples from non-human primates that chronically self-administer high levels of ethanol. Two-dimensional difference in-gel electrophoresis (2D-DIGE) was used to quantify plasma proteins from within-subject samples collected before exposure to ethanol and after 3 months of excessive ethanol self-administration. Highly abundant plasma proteins were depleted from plasma samples to increase proteomic coverage. Altered plasma levels of serum amyloid A4 (SAA4), retinol-binding protein, inter-alpha inhibitor H4, clusterin, and fibronectin, identified by 2D-DIGE analysis, were confirmed in unmanipulated, whole plasma from these animals by immunoblotting. Examination of these target plasma proteins in human subjects with excessive alcohol consumption (and control subjects) revealed increased levels of SAA4 and clusterin and decreased levels of fibronectin compared to controls. These proteins not only serve as targets for further development as biomarker candidates or components of biomarker panels, but also add to the growing understanding of dysregulated immune function and lipoprotein metabolism with chronic, excessive alcohol consumption.

  15. DINOFLAGELLATE CYST RECORD AND HUMAN DISTURBANCE IN NEW BEDFORD HARBOR, MA AND NARRAGANSETT BAY ESTUARIES

    Science.gov (United States)

    We studied the dinoflagellate cyst records in sediments from New Bedford Harbor and Apponagansett Bay over the last 350 yr provides to determine if cysts are sensitive to environmental change caused by human activity in the watershed. Changes in the total number, and absolute and...

  16. Effect of contractile protein alterations on cardiac myofilament function in human heart failure

    NARCIS (Netherlands)

    Narolska, N.A.

    2006-01-01

    The main objective of this thesis was to elucidate the effect of translational and post-translational alterations in contractile proteins occurring during heart failure on contractile function in human cardiac tissue. Isometric force and ATPase activity measurements were performed in skinned human

  17. Alterations of p63 and p73 in human cancers.

    Science.gov (United States)

    Inoue, Kazushi; Fry, Elizabeth A

    2014-01-01

    p53 and its related genes, p63 and p73 constitute the p53 gene family. While p53 is the most frequently mutated gene in human tumors, p63 and p73 are rarely mutated or deleted in cancers. Many studies have reported p63/p73 overexpression in human cancers while others showed that a loss of p63/p73 is associated with tumor progression and metastasis. Thus, whether p63 or p73 is a tumor suppressor gene or an oncogene has been a matter of debate. This controversy has been attributed to the existence of multiple splicing isoforms with distinct functions; the full-length TA isoform of p63 has structural and functional similarity to wild-type p53, whereas the ΔNp63 acts primarily in dominant-negative fashion against all family members of p53. Differential activities of TA and ΔN isoforms have been shown in vivo by creating isform-specific gene knockout mice. All p53, p63, p73 proteins bind to and activate target genes with p53-response elements; p63 also binds to distinct p63-response elements and regulate expression of specific target genes involved in skin, limb, and craniofacial development. Interestingly, several studies have shown that both p63 and p73 are involved in cellular response to cancer therapy and others have indicated that both of these molecules are required for p53-induced apoptosis, suggesting functional interplay among p53 family proteins. Consistent with these findings, aberrant splicing that result in ΔNp63 or ΔNp73 overexpression are frequently found in human cancers, and is associated with poor clinical outcomes of patients in the latter. Thus immunohistochemical staining of tumor specimen with ΔNp73-specific antibody might have diagnostic values in cancer clinics.

  18. Somatic retrotransposition alters the genetic landscape of the human brain.

    Science.gov (United States)

    Baillie, J Kenneth; Barnett, Mark W; Upton, Kyle R; Gerhardt, Daniel J; Richmond, Todd A; De Sapio, Fioravante; Brennan, Paul M; Rizzu, Patrizia; Smith, Sarah; Fell, Mark; Talbot, Richard T; Gustincich, Stefano; Freeman, Thomas C; Mattick, John S; Hume, David A; Heutink, Peter; Carninci, Piero; Jeddeloh, Jeffrey A; Faulkner, Geoffrey J

    2011-10-30

    Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells, excluding early embryo development and some malignancies. Recent reports of L1 expression and copy number variation in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 SVA insertions. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes.

  19. Microstimulation of the human substantia nigra alters reinforcement learning.

    Science.gov (United States)

    Ramayya, Ashwin G; Misra, Amrit; Baltuch, Gordon H; Kahana, Michael J

    2014-05-14

    Animal studies have shown that substantia nigra (SN) dopaminergic (DA) neurons strengthen action-reward associations during reinforcement learning, but their role in human learning is not known. Here, we applied microstimulation in the SN of 11 patients undergoing deep brain stimulation surgery for the treatment of Parkinson's disease as they performed a two-alternative probability learning task in which rewards were contingent on stimuli, rather than actions. Subjects demonstrated decreased learning from reward trials that were accompanied by phasic SN microstimulation compared with reward trials without stimulation. Subjects who showed large decreases in learning also showed an increased bias toward repeating actions after stimulation trials; therefore, stimulation may have decreased learning by strengthening action-reward associations rather than stimulus-reward associations. Our findings build on previous studies implicating SN DA neurons in preferentially strengthening action-reward associations during reinforcement learning.

  20. Assessment of ecological and human health risks of heavy metal contamination in agriculture soils disturbed by pipeline construction.

    Science.gov (United States)

    Shi, Peng; Xiao, Jun; Wang, Yafeng; Chen, Liding

    2014-02-28

    The construction of large-scale infrastructures such as nature gas/oil pipelines involves extensive disturbance to regional ecosystems. Few studies have documented the soil degradation and heavy metal contamination caused by pipeline construction. In this study, chromium (Cr), cadmium (Cd), copper (Cu), nickel (Ni), lead (Pb) and zinc (Zn) levels were evaluated using Index of Geo-accumulation (Igeo) and Potential Ecological Risk Index (RI) values, and human health risk assessments were used to elucidate the level and spatial variation of heavy metal pollution risks. The results showed that the impact zone of pipeline installation on soil heavy metal contamination was restricted to pipeline right-of-way (RoW), which had higher Igeo of Cd, Cu, Ni and Pb than that of 20 m and 50 m. RI showed a declining tendency in different zones as follows: trench > working zone > piling area > 20 m > 50 m. Pipeline RoW resulted in higher human health risks than that of 20 m and 50 m, and children were more susceptible to non-carcinogenic hazard risk. Cluster analysis showed that Cu, Ni, Pb and Cd had similar sources, drawing attention to the anthropogenic activity. The findings in this study should help better understand the type, degree, scope and sources of heavy metal pollution from pipeline construction to reduce pollutant emissions, and are helpful in providing a scientific basis for future risk management.

  1. Assessment of Ecological and Human Health Risks of Heavy Metal Contamination in Agriculture Soils Disturbed by Pipeline Construction

    Directory of Open Access Journals (Sweden)

    Peng Shi

    2014-02-01

    Full Text Available The construction of large-scale infrastructures such as nature gas/oil pipelines involves extensive disturbance to regional ecosystems. Few studies have documented the soil degradation and heavy metal contamination caused by pipeline construction. In this study, chromium (Cr, cadmium (Cd, copper (Cu, nickel (Ni, lead (Pb and zinc (Zn levels were evaluated using Index of Geo-accumulation (Igeo and Potential Ecological Risk Index (RI values, and human health risk assessments were used to elucidate the level and spatial variation of heavy metal pollution risks. The results showed that the impact zone of pipeline installation on soil heavy metal contamination was restricted to pipeline right-of-way (RoW, which had higher Igeo of Cd, Cu, Ni and Pb than that of 20 m and 50 m. RI showed a declining tendency in different zones as follows: trench > working zone > piling area > 20 m > 50 m. Pipeline RoW resulted in higher human health risks than that of 20 m and 50 m, and children were more susceptible to non-carcinogenic hazard risk. Cluster analysis showed that Cu, Ni, Pb and Cd had similar sources, drawing attention to the anthropogenic activity. The findings in this study should help better understand the type, degree, scope and sources of heavy metal pollution from pipeline construction to reduce pollutant emissions, and are helpful in providing a scientific basis for future risk management.

  2. Assessment of Ecological and Human Health Risks of Heavy Metal Contamination in Agriculture Soils Disturbed by Pipeline Construction

    Science.gov (United States)

    Shi, Peng; Xiao, Jun; Wang, Yafeng; Chen, Liding

    2014-01-01

    The construction of large-scale infrastructures such as nature gas/oil pipelines involves extensive disturbance to regional ecosystems. Few studies have documented the soil degradation and heavy metal contamination caused by pipeline construction. In this study, chromium (Cr), cadmium (Cd), copper (Cu), nickel (Ni), lead (Pb) and zinc (Zn) levels were evaluated using Index of Geo-accumulation (Igeo) and Potential Ecological Risk Index (RI) values, and human health risk assessments were used to elucidate the level and spatial variation of heavy metal pollution risks. The results showed that the impact zone of pipeline installation on soil heavy metal contamination was restricted to pipeline right-of-way (RoW), which had higher Igeo of Cd, Cu, Ni and Pb than that of 20 m and 50 m. RI showed a declining tendency in different zones as follows: trench > working zone > piling area > 20 m > 50 m. Pipeline RoW resulted in higher human health risks than that of 20 m and 50 m, and children were more susceptible to non-carcinogenic hazard risk. Cluster analysis showed that Cu, Ni, Pb and Cd had similar sources, drawing attention to the anthropogenic activity. The findings in this study should help better understand the type, degree, scope and sources of heavy metal pollution from pipeline construction to reduce pollutant emissions, and are helpful in providing a scientific basis for future risk management. PMID:24590049

  3. Disturbed α-Cell Function in Mice with β-Cell Specific Overexpression of Human Islet Amyloid Polypeptide

    Directory of Open Access Journals (Sweden)

    Bo Ahrén

    2008-01-01

    Full Text Available Exogenous administration of islet amyloid polypeptide (IAPP has been shown to inhibit both insulin and glucagon secretion. This study examined α-cell function in mice with β-cell specific overexpression of human IAPP (hIAPP after an oral protein gavage (75 mg whey protein/mouse. Baseline glucagon levels were higher in transgenic mice (41±4.0 pg/mL, n=6 than in wildtype animals (19±5.1 pg/mL, n=5, P=.015. In contrast, the glucagon response to protein was impaired in transgenic animals (21±2.7 pg/mL in transgenic mice versus 38±5.7 pg/mL in wildtype mice at 15 minutes; P=.027. Baseline insulin levels did not differ between the groups, while the insulin response, as the glucagon response, was impaired after protein challenge (P=.018. Glucose levels were not different between the groups and did not change significantly after protein gavage. Acetaminophen was given through gavage to the animals (2 mg/mouse to estimate gastric emptying. The plasma acetaminophen profile was similar in the two groups of mice. We conclude that disturbances in glucagon secretion exist in mice with β-cell specific overexpression of human IAPP, which are not secondary to changes in gastric emptying. The reduced glucagon response to protein challenge may reflect a direct inhibitory influence of hIAPP on glucagon secretion.

  4. Floodplain geomorphic processes and environmental impacts of human alteration along coastal plain rivers, USA

    Science.gov (United States)

    Hupp, C.R.; Pierce, A.R.; Noe, G.B.

    2009-01-01

    Human alterations along stream channels and within catchments have affected fluvial geomorphic processes worldwide. Typically these alterations reduce the ecosystem services that functioning floodplains provide; in this paper we are concerned with the sediment and associated material trapping service. Similarly, these alterations may negatively impact the natural ecology of floodplains through reductions in suitable habitats, biodiversity, and nutrient cycling. Dams, stream channelization, and levee/canal construction are common human alterations along Coastal Plain fluvial systems. We use three case studies to illustrate these alterations and their impacts on floodplain geomorphic and ecological processes. They include: 1) dams along the lower Roanoke River, North Carolina, 2) stream channelization in west Tennessee, and 3) multiple impacts including canal and artificial levee construction in the central Atchafalaya Basin, Louisiana. Human alterations typically shift affected streams away from natural dynamic equilibrium where net sediment deposition is, approximately, in balance with net erosion. Identification and understanding of critical fluvial parameters (e.g., stream gradient, grain-size, and hydrography) and spatial and temporal sediment deposition/erosion process trajectories should facilitate management efforts to retain and/or regain important ecosystem services. ?? 2009, The Society of Wetland Scientists.

  5. Embryonic atrazine exposure alters zebrafish and human miRNAs associated with angiogenesis, cancer, and neurodevelopment.

    Science.gov (United States)

    Wirbisky, Sara E; Weber, Gregory J; Schlotman, Kelly E; Sepúlveda, Maria S; Freeman, Jennifer L

    2016-12-01

    MicroRNAs (miRNAs) are short, single-stranded RNA that regulate post-transcriptional control of mRNA translation. Knowledge on the role of these critical regulators in toxicological responses in increasing, but is still limited. Atrazine is a herbicide used throughout the Midwestern US that is reported to frequently contaminate potable water supplies above the maximum contaminant level of 3 parts per billion. Atrazine is a suspected endocrine disrupting chemical and studies have begun to investigate the genetic mechanisms of toxicity; however, studies investigating epigenetic mechanisms are limited. In this study both zebrafish and human miRNAs were significantly altered in response to an embryonic atrazine exposure of 0.3, 3, or 30 ppb in zebrafish. Altered miRNAs are known to play a role in angiogenesis, cancer, or neuronal development, differentiation, and maturation. Targeted analysis of altered human miRNAs with genes previously identified to be altered by atrazine exposure revealed several targets linked to cell cycle and cell signaling. Further analysis of hsa-miRNA-126-3p, which had altered expression in all three atrazine treatments at 72 hpf, revealed alterations also occurred at 60 hpf in the 30 ppb treatment group. Results from this study indicate miRNA deregulation in zebrafish and human miRNAs following an embryonic atrazine exposure in zebrafish. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Human Catestatin Alters Gut Microbiota Composition in Mice

    Science.gov (United States)

    Rabbi, Mohammad F.; Munyaka, Peris M.; Eissa, Nour; Metz-Boutigue, Marie-Hélène; Khafipour, Ehsan; Ghia, Jean Eric

    2017-01-01

    The mammalian intestinal tract is heavily colonized with a dense, complex, and diversified microbial populations. In healthy individuals, an array of epithelial antimicrobial agents is secreted in the gut to aid intestinal homeostasis. Enterochromaffin cells (EC) in the intestinal epithelium are a major source of chromogranin A (CgA), which is a pro-hormone and can be cleaved into many bioactive peptides that include catestatin (CST). This study was carried out to evaluate the possible impact of CST on gut microbiota in vivo using a mouse model. The CST (Human CgA352−372) or normal saline was intrarectally administered in C57BL/6 male mice for 6 days and then sacrificed. Feces and colonic mucosa tissue samples were collected, DNA was extracted, the V4 region of bacterial 16S rRNA gene was amplified and subjected to MiSeq Illumina sequencing. The α-diversity was calculated using Chao 1 and β-diversity was determined using QIIME. Differences at the genus level were determined using partial least square discriminant analysis (PLS-DA). Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used to predict functional capacity of bacterial community. CST treatment did not modify bacterial richness in fecal and colonic mucosa-associated microbiota; however, treatment significantly modified bacterial community composition between the groups. Also, CST-treated mice had a significantly lower relative abundance of Firmicutes and higher abundance of Bacteroidetes, observed only in fecal samples. However, at lower phylogenetic levels, PLS-DA analysis revealed that some bacterial taxa were significantly associated with the CST-treated mice in both fecal and colonic mucosa samples. In addition, differences in predicted microbial functional pathways in both fecal and colonic mucosa samples were detected. The results support the hypothesis that CST treatment modulates gut microbiota composition under non-pathophysiological conditions

  7. Emotional Disturbance

    Science.gov (United States)

    ... skills, and increase self-awareness, self-control, and self-esteem. A large body of research exists regarding methods ... not. Back to top Other Considerations Children and adolescents with an emotional disturbance should receive services based ...

  8. A modelling framework to evaluate human-induced alterations of network sediment connectivity and quantify their unplanned adverse impact

    Science.gov (United States)

    Bizzi, S.; Schmitt, R. J. P.; Giuliani, M.; Castelletti, A.

    2016-12-01

    World-wide human-induced alterations of sediment transport, e.g. due to dams, sand and gravel mining along rivers and channel maintenance, translated into geomorphic changes, which have had major effects on ecosystem integrity, human livelihoods, ultimately negatively impacting also on the expected benefit from building water infrastructures. Despite considerable recent advances in modelling basin-scale hydrological and geomorphological processes, our ability to quantitatively simulate network sediment transport, foresee effects of alternative scenarios of human development on fluvial morpho-dynamics, and design anticipatory planning adaptation measures is still limited. In this work, we demonstrate the potential of a novel modelling framework called CASCADE (CAtchment SEdiment Connectivity And Delivery (Schmitt et al., 2016)) to characterize sediment connectivity at the whole river network scale, predict the disturbing effect of dams on the sediment transport, and quantify the associated loss with respect to the level of benefits that provided the economic justification for their development. CASCADE allows tracking the fate of a sediment from its source to its multiple sinks across the network. We present the results from two major, transboundary river systems (3S and Red River) in South-East Asia. We first discuss the ability of CASCADE to properly represent sediment connectivity at the network scale using available remote sensing data and information from monitoring networks. Secondly, we assess the impacts on sediment connectivity induced by existing and planned dams in the 3S and Red River basins and compare these alterations with revenues in terms of hydropower production. CASCADE outputs support a broader understanding of sediment connectivity tailored for water management issues not yet available, and it is suitable to enrich assessments of food-energy-water nexus. The model framework can be embedded into the design of optimal siting and sizing of water

  9. Human disturbance and upward expansion of plants in a warming climate

    Science.gov (United States)

    Dainese, Matteo; Aikio, Sami; Hulme, Philip E.; Bertolli, Alessio; Prosser, Filippo; Marini, Lorenzo

    2017-08-01

    Climate change is expected to trigger an upward expansion of plants in mountain regions and, although there is strong evidence that many native species have already shifted their distributions to higher elevations, little is known regarding how fast non-native species might respond to climate change. By analysing 131,394 occurrence records of 1,334 plant species collected over 20 years in the European Alps, we found that non-natives are spreading upwards approximately twice as fast as natives. Whereas the spread of natives was enhanced by traits favouring longer dispersal distances, this was not the case for non-natives. This was due to the non-native species pool already being strongly biased towards species that had traits facilitating spread. A large proportion of native and non-native species seemed to be able to spread upwards faster than the current velocity of climate change. In particular, long-distance dispersal events and proximity to roads proved to be key drivers for the observed rapid spread. Our findings highlight that invasions by non-native species into native alpine communities are a potentially significant additional pressure on these vulnerable ecosystems that are already likely to suffer dramatic vegetation changes with ongoing warming and increasing human activity in mountain regions.

  10. Heterophil/Lymphocyte Alterations as a Measure of Stress in American Alligators in Relation to Anthropogenic Disturbance in a Louisiana Intermediate Marsh

    Directory of Open Access Journals (Sweden)

    Christopher M. Murray

    2015-05-01

    Full Text Available Numerous anthropogenic factors represent environmental threats to Gulf Coast wetland ecosystems and associated fauna. American alligators (Alligator mississippiensis have been subject to long-term management and used as ecological and physiological indicators of habitat quality in response to anthropogenic events and stochastic natural disasters. The present study monitored heterophil to lymphocyte ratios (an indicator of stress, in American alligators in a Louisiana intermediate marsh from 2009 to 2011, a time period that coincides with an oil inundation event that occurred in 2011. Sixteen alligators were observed and processed morphometrically (total length, snout-vent length and body mass. Heterophil to lymphocyte ratios were negatively correlated with size, suggesting larger American alligators were physiologically more resilient to the disturbance, more able to actively avoid these poor conditions, or are less affected by localized disturbance.

  11. Evidences that human disturbance simplify the ant fauna associated a Stachytarpheta glabra Cham. (Verbenaceae compromising the benefits of ant-plant mutualism

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    BC. Barbosa

    Full Text Available Interaction among species, like ants and plants through extrafloral nectaries (EFNs, are important components of ecological communities’ evolution. However, the effect of human disturbance on such specific interactions and its ecological consequences is poorly understood. This study evaluated the outcomes of mutualism between ants and the EFN-bearing plant Stachytarpheta glabra under anthropogenic disturbance. We compared the arthropod fauna composition between two groups of twenty plant individuals, one in an area disturbed by human activities and one in a preserved area. We also check the plant investment in herbivory defense and the consequential leaf damage by herbivore. Our results indicate that such disturbances cause simplification of the associated fauna and lack of proper ant mutualist. This led to four times more herbivory on plants of disturbed areas, despite the equal amount of EFN and ant visitors and low abundance of herbivores. The high pressure of herbivory may difficult the re-establishment of S. glabra, an important pioneer species in ferruginous fields, therefore it may affect resilience of this fragile ecological community.

  12. Evidences that human disturbance simplify the ant fauna associated a Stachytarpheta glabra Cham. (Verbenaceae) compromising the benefits of ant-plant mutualism.

    Science.gov (United States)

    Barbosa, B C; Fagundes, R; Silva, L F; Tofoli, J F V; Santos, A M; Imai, B Y P; Gomes, G G; Hermidorff, M M; Ribeiro, S P

    2015-01-01

    Interaction among species, like ants and plants through extrafloral nectaries (EFNs), are important components of ecological communities' evolution. However, the effect of human disturbance on such specific interactions and its ecological consequences is poorly understood. This study evaluated the outcomes of mutualism between ants and the EFN-bearing plant Stachytarpheta glabra under anthropogenic disturbance. We compared the arthropod fauna composition between two groups of twenty plant individuals, one in an area disturbed by human activities and one in a preserved area. We also check the plant investment in herbivory defense and the consequential leaf damage by herbivore. Our results indicate that such disturbances cause simplification of the associated fauna and lack of proper ant mutualist. This led to four times more herbivory on plants of disturbed areas, despite the equal amount of EFN and ant visitors and low abundance of herbivores. The high pressure of herbivory may difficult the re-establishment of S. glabra, an important pioneer species in ferruginous fields, therefore it may affect resilience of this fragile ecological community.

  13. Community-level response to different human disturbances and land use of small mammals in two marshland habitat patches in Hungary

    Directory of Open Access Journals (Sweden)

    Horváth G.F.

    2012-01-01

    Full Text Available Marshlands are important ecosystems that provide valuable habitats for wildlife communities. We investigated the small mammal community-level response to different human disturbances and land use in the Kis-Balaton Landscape Protection Area, which is an endangered marshland ecosystem of Hungary. Land use, conservation management and other human disturbances (burning, mowing together with unfavorable weather conditions have caused the degradation of the original homogeneous sedgy marshland on both sampled areas. We measured the species turnover between the different periods separated by the habitat changes. Our results suggest that populations of the habitat-specialist species of marshland areas (e.g. endangered Hungarian subspecies of root vole are sensitive to the negative effects of environment and human disturbances. The combined effect of human disturbances and the stochastic processes of the environment can cause the disappearance and substitution of character species stabilizing the communities, which in turn leads to the modification of species composition and structure of small mammal assemblages.

  14. Distribution of a Community of Mammals in Relation to Roads and Other Human Disturbances in Gabon, Central Africa

    Science.gov (United States)

    Vanthomme, Hadrien; Kolowski, Joseph; Korte, Lisa; Alonso, Alfonso

    2013-01-01

    Abstract We present the first community-level study of the associations of both roads and other human disturbances with the distribution of mammals in Gabon (central Africa). Our study site was in an oil concession within a littoral mosaic landscape. We conducted surveys along 199 line transects and installed camera traps on 99 of these transects to document mammal presence and abundance. We used generalized linear mixed-effect models to document associations between variables related to the ecosystem (land cover, topography, and hydrology), roads (coating, width of rights of way, condition, type of vehicle used on the road, traffic level, affiliation of users, and general type of road), and other human disturbances (urbanization, agriculture, hunting, logging, gathering, and industrial activities) and the abundance or presence of 17 species or groups of mammals including elephant (Loxodonta cyclotis), buffalo (Syncerus caffer), sitatunga (Tragelaphus spekei), red river hog (Potamochoerus porcus), smaller ungulates, gorilla (Gorilla gorilla), chimpanzee (Pan troglodytes), side-striped jackal (Canis adustus), carnivores, monkeys, and large rodents. Some types of roads and other human disturbances were negatively associated with the abundance or presence of elephants, buffalos, gorillas, sitatungas, some monkeys, and duikers. The pattern of associations of mammals with roads and other human disturbances was diverse and included positive associations with road presence (red river hog, some monkeys, and duikers), agriculture (sitatunga, small carnivores, and large rodents) and industrial activities (sitatunga, red river hog, red duikers, and side-striped jackal). Our results suggest that the community of mammals we studied was mostly affected by hunting, agriculture, and urbanization, which are facilitated by road presence. We recommend increased regulation of agriculture, hunting, and road building in the area. Distribución de una Comunidad de Mamíferos en Relaci

  15. Release of Tensile Strain on Engineered Human Tendon Tissue Disturbs Cell Adhesions, Changes Matrix Architecture, and Induces an Inflammatory Phenotype

    Science.gov (United States)

    Bayer, Monika L.; Schjerling, Peter; Herchenhan, Andreas; Zeltz, Cedric; Heinemeier, Katja M.; Christensen, Lise; Krogsgaard, Michael; Gullberg, Donald; Kjaer, Michael

    2014-01-01

    Mechanical loading of tendon cells results in an upregulation of mechanotransduction signaling pathways, cell-matrix adhesion and collagen synthesis, but whether unloading removes these responses is unclear. We investigated the response to tension release, with regard to matrix proteins, pro-inflammatory mediators and tendon phenotypic specific molecules, in an in vitro model where tendon-like tissue was engineered from human tendon cells. Tissue sampling was performed 1, 2, 4 and 6 days after surgical de-tensioning of the tendon construct. When tensile stimulus was removed, integrin type collagen receptors showed a contrasting response with a clear drop in integrin subunit α11 mRNA and protein expression, and an increase in α2 integrin mRNA and protein levels. Further, specific markers for tendon cell differentiation declined and normal tendon architecture was disturbed, whereas pro-inflammatory molecules were upregulated. Stimulation with the cytokine TGF-β1 had distinct effects on some tendon-related genes in both tensioned and de-tensioned tissue. These findings indicate an important role of mechanical loading for cellular and matrix responses in tendon, including that loss of tension leads to a decrease in phenotypical markers for tendon, while expression of pro-inflammatory mediators is induced. PMID:24465881

  16. Human Disturbance Threats the Red-Listed Macrolichen Seirophora villosa (Ach.) Frödén in Coastal Juniperus Habitats: Evidence From Western Peninsular Italy

    Science.gov (United States)

    Benesperi, Renato; Lastrucci, Lorenzo; Nascimbene, Juri

    2013-10-01

    In Europe, coastal dune systems with Juniperus spp. (Natura 2000 habitat code 2250) are a priority habitat for conservation according to the Natura 2000 policies. Currently, anthropogenic pressure is threatening the biodiversity of this habitat. While the impact of human pressure on animals and vascular plants is already documented, information is still scanty for other organisms such as epiphytic lichens. The main aim of this study is to test the effect of human disturbance on the occurrence and abundance of the red-listed macrolichen Seirophora villosa. We also tested the effect of human disturbance on the whole community of epiphytic lichens in terms of species richness and composition. The study was performed along the coast of Tuscany by comparing both disturbed and undisturbed Juniperus stands according to a stratified random sampling design. Our results provided evidence that in coastal systems the long-term conservation of the red-listed macrolichen S. villosa and its characteristic community composed by several Mediterranean species of conservation concern depends on the maintenance of undisturbed Juniperus habitats. Results also support the possibility of using S. villosa as an indicator species of habitat conservation importance and habitat integrity since its occurrence is predicted on nestedness in term of species composition, assemblages of species poor disturbed stands being subsets of those of richer undisturbed stands.

  17. Quantification of color alteration in human teeth with optical coherence tomography

    Science.gov (United States)

    Ni, Y. R.; Guo, Z. Y.; Shu, S. Y.; Zeng, C. C.; Zhong, H. Q.; Chen, B. L.; Liu, Z. M.; Bao, Y.

    2011-11-01

    It is necessary to develop a laboratory model to evaluate tooth discoloration, because there are several limitations to assessment methods at present stage. Therefore, in this letter, we report the results from a pilot study on using optical coherence tomography imaging method to quantify color alteration in the human teeth treatment with 35% hydrogen peroxide bleaching in vitro. Quantitative comparison of chromogens reduction in dental tissue showed that near infrared attenuation coefficient (μ) increased for enamel with the bleaching passage time and diminution for dentine. Therefore, the precise detection of the change in attenuation coefficient is can accurate quantitative chromogens alteration in tooth. OCT has a potential to become a useful tool for the assessment color alteration in human teeth.

  18. Chlorobenzenes, lindane and dieldrin induce apoptotic alterations in human peripheral blood lymphocytes (in vitro study).

    Science.gov (United States)

    Michałowicz, Jaromir; Mokra, Katarzyna; Rosiak, Karolina; Sicińska, Paulina; Bukowska, Bożena

    2013-11-01

    In this study, we have assessed apoptotic effect of 1,2,4-trichlorobenzene, hexachlorobenzene, lindane and dieldrin on human peripheral blood lymphocytes. We observed an increase in ROS formation and a decrease in mitochondrial transmembrane potential in the cells incubated with low concentrations of all compounds studied, in particular lindane and dieldrin. ROS formation and changes in mitochondrial transmembrane potential may have influenced caspase-3 activation, a crucial enzyme in the apoptotic process. Moreover, chlorobenzenes, and in particular lindane and dieldrin changed cells' membrane permeability and induced phosphatidylserine translocation, which confirmed that they are capable of inducing apoptosis in human lymphocytes. Apoptotic changes in human lymphocytes provoked by biologically relevant concentrations of these substances suggest that they may disturb function of immunological system especially among people occupationally exposed to their action. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Altered snowfall and soil disturbance influence the early life stage transitions and recruitment of a native and invasive grass in a cold desert.

    Science.gov (United States)

    Gornish, Elise S; Aanderud, Zachary T; Sheley, Roger L; Rinella, Mathew J; Svejcar, Tony; Englund, Suzanne D; James, Jeremy J

    2015-02-01

    Climate change effects on plants are expected to be primarily mediated through early life stage transitions. Snowfall variability, in particular, may have profound impacts on seedling recruitment, structuring plant populations and communities, especially in mid-latitude systems. These water-limited and frequently invaded environments experience tremendous variation in snowfall, and species in these systems must contend with harsh winter conditions and frequent disturbance. In this study, we examined the mechanisms driving the effects of snowpack depth and soil disturbance on the germination, emergence, and establishment of the native Pseudoroegnaria spicata and the invasive Bromus tectorum, two grass species that are widely distributed across the cold deserts of North America. The absence of snow in winter exposed seeds to an increased frequency and intensity of freeze-thaw cycles and greater fungal pathogen infection. A shallower snowpack promoted the formation of a frozen surface crust, reducing the emergence of both species (more so for P. spicata). Conversely, a deeper snowpack recharged the soil and improved seedling establishment of both species by creating higher and more stable levels of soil moisture availability following spring thaw. Across several snow treatments, experimental disturbance served to decrease the cumulative survival of both species. Furthermore, we observed that, regardless of snowpack treatment, most seed mortality (70-80%) occurred between seed germination and seedling emergence (November-March), suggesting that other wintertime factors or just winter conditions in general limited survival. Our results suggest that snowpack variation and legacy effects of the snowpack influence emergence and establishment but might not facilitate invasion of cold deserts.

  20. Human Ozone (O3) Exposure Alters Serum Profile of Lipid Metabolites

    Science.gov (United States)

    HUMAN OZONE (O3) EXPOSURE ALTERS SERUM PROFILE OF LIPID METABOLITES Miller, D B.1; Kodavanti, U P.2 Karoly, E D.3; Cascio W.E2, Ghio, A J. 21. UNC-Chapel Hill, Chapel Hill, N.C., United States. 2. NHEERL, U.S. EPA, RTP, N.C., United States. 3. METABOLON INC., Durham, N.C., United...

  1. Human Ozone (O3) Exposure Alters Serum Profile of Lipid Metabolites

    Science.gov (United States)

    HUMAN OZONE (O3) EXPOSURE ALTERS SERUM PROFILE OF LIPID METABOLITES Miller, D B.1; Kodavanti, U P.2 Karoly, E D.3; Cascio W.E2, Ghio, A J. 21. UNC-Chapel Hill, Chapel Hill, N.C., United States. 2. NHEERL, U.S. EPA, RTP, N.C., United States. 3. METABOLON INC., Durham, N.C., United...

  2. Human disturbances, habitat characteristics and social environment generate sex-specific responses in vigilance of Mediterranean mouflon.

    Science.gov (United States)

    Benoist, Stéphanie; Garel, Mathieu; Cugnasse, Jean-Marc; Blanchard, Pierrick

    2013-01-01

    In prey species, vigilance is an important part of the decision making process related to predation risk effects. Therefore, understanding the mechanisms shaping vigilance behavior provides relevant insights on factors influencing individual fitness. We investigated the role of extrinsic and intrinsic factors on vigilance behavior in Mediterranean mouflon (Ovis gmelini musimon×Ovis sp.) in a study site spatially and temporally contrasted in human pressures. Both sexes were less vigilant in the wildlife reserve compared to surrounding unprotected areas, except for males during the hunting period. During this period, males tended to be less strictly restricted to the reserve than females what might lead to a pervasive effect of hunting within the protected area, resulting in an increase in male vigilance. It might also be a rutting effect that did not occur in unprotected areas because males vigilance was already maximal in response to human disturbances. In both sexes, yearlings were less vigilant than adults, probably because they traded off vigilance for learning and energy acquisition and/or because they relied on adult experience present in the group. Similarly, non-reproductive females benefited of the vigilance effort provided by reproductive females when belonging to the same group. However, in the absence of reproductive females, non-reproductive females were as vigilant as reproductive females. Increasing group size was only found to reduce vigilance in females (up to 17.5%), not in males. We also showed sex-specific responses to habitat characteristics. Females increased their vigilance when habitat visibility decreased (up to 13.8%) whereas males increased their vigilance when feeding on low quality sites, i.e., when concomitant increase in chewing time can be devoted to vigilance with limited costs. Our global approach was able to disentangle the sex-specific sources of variation in mouflon vigilance and stressed the importance of reserves in managing

  3. Human disturbances, habitat characteristics and social environment generate sex-specific responses in vigilance of Mediterranean mouflon.

    Directory of Open Access Journals (Sweden)

    Stéphanie Benoist

    Full Text Available In prey species, vigilance is an important part of the decision making process related to predation risk effects. Therefore, understanding the mechanisms shaping vigilance behavior provides relevant insights on factors influencing individual fitness. We investigated the role of extrinsic and intrinsic factors on vigilance behavior in Mediterranean mouflon (Ovis gmelini musimon×Ovis sp. in a study site spatially and temporally contrasted in human pressures. Both sexes were less vigilant in the wildlife reserve compared to surrounding unprotected areas, except for males during the hunting period. During this period, males tended to be less strictly restricted to the reserve than females what might lead to a pervasive effect of hunting within the protected area, resulting in an increase in male vigilance. It might also be a rutting effect that did not occur in unprotected areas because males vigilance was already maximal in response to human disturbances. In both sexes, yearlings were less vigilant than adults, probably because they traded off vigilance for learning and energy acquisition and/or because they relied on adult experience present in the group. Similarly, non-reproductive females benefited of the vigilance effort provided by reproductive females when belonging to the same group. However, in the absence of reproductive females, non-reproductive females were as vigilant as reproductive females. Increasing group size was only found to reduce vigilance in females (up to 17.5%, not in males. We also showed sex-specific responses to habitat characteristics. Females increased their vigilance when habitat visibility decreased (up to 13.8% whereas males increased their vigilance when feeding on low quality sites, i.e., when concomitant increase in chewing time can be devoted to vigilance with limited costs. Our global approach was able to disentangle the sex-specific sources of variation in mouflon vigilance and stressed the importance of

  4. Inhibition of α-adrenergic tone disturbs the distribution of blood flow in the exercising human limb.

    Science.gov (United States)

    Heinonen, Ilkka; Wendelin-Saarenhovi, Maria; Kaskinoro, Kimmo; Knuuti, Juhani; Scheinin, Mika; Kalliokoski, Kari K

    2013-07-15

    The role of neuronal regulation of human cardiovascular function remains incompletely elucidated, especially during exercise. Here we, by positron emission tomography, monitored tissue-specific blood flow (BF) changes in nine healthy young men during femoral arterial infusions of norepinephrine (NE) and phentolamine. At rest, the α-adrenoceptor agonist NE reduced BF by ~40%, similarly in muscles (from 3.2 ± 1.9 to 1.4 ± 0.3 ml·min(-1)·100 g(-1) in quadriceps femoris muscle), bone (from 1.1 ± 0.4 to 0.5 ± 0.2 ml·min(-1)·100 g(-1)) and adipose tissue (AT) (from 1.2 ± 0.7 to 0.7 ± 0.3 ml·min(-1)·100 g(-1)). During exercise, NE reduced exercising muscle BF by ~16%. BF in AT was reduced similarly as rest. The α-adrenoceptor antagonist phentolamine increased BF similarly in the different muscles and other tissues of the limb at rest. During exercise, BF in inactive muscle was increased 3.4-fold by phentolamine compared with exercise without drug, but BF in exercising muscles was not influenced. Bone and AT (P = 0.055) BF were also increased by phentolamine in the exercise condition. NE increased and phentolamine decreased oxygen extraction in the limb during exercise. We conclude that inhibition of α-adrenergic tone markedly disturbs the distribution of BF and oxygen extraction in the exercising human limb by increasing BF especially around inactive muscle fibers. Moreover, although marked functional sympatholysis also occurs during exercise, the arterial NE infusion that mimics the exaggerated sympathetic nerve activity commonly seen in patients with cardiovascular disease was still capable of directly limiting BF in the exercising leg muscles.

  5. Vegetation cover and topography rather than human disturbance control gully density and sediment production on the Chinese Loess Plateau

    Science.gov (United States)

    Zhao, Jianlin; Vanmaercke, Matthias; Chen, Longqian; Govers, Gerard

    2016-12-01

    absence of a clear climate signal, both with respect to the variation in gully density and in E, can be explained by the overwhelming effect that climate has on vegetation cover. Our research showed that non-topsoil erosion processes are the dominant sediment sources on the CLP and are strongly controlled by natural factors. The effect of human disturbance on non-topsoil erosion processes is far less important than its effect on topsoil erosion. Given the dominance of non-topsoil erosion processes on the CLP, this suggests that the high sediment production of the CLP is mainly attributable to natural factors.

  6. Impact of DNA mismatch repair system alterations on human fertility and related treatments.

    Science.gov (United States)

    Hu, Min-hao; Liu, Shu-yuan; Wang, Ning; Wu, Yan; Jin, Fan

    2016-01-01

    DNA mismatch repair (MMR) is one of the biological pathways, which plays a critical role in DNA homeostasis, primarily by repairing base-pair mismatches and insertion/deletion loops that occur during DNA replication. MMR also takes part in other metabolic pathways and regulates cell cycle arrest. Defects in MMR are associated with genomic instability, predisposition to certain types of cancers and resistance to certain therapeutic drugs. Moreover, genetic and epigenetic alterations in the MMR system demonstrate a significant relationship with human fertility and related treatments, which helps us to understand the etiology and susceptibility of human infertility. Alterations in the MMR system may also influence the health of offspring conceived by assisted reproductive technology in humans. However, further studies are needed to explore the specific mechanisms by which the MMR system may affect human infertility. This review addresses the physiological mechanisms of the MMR system and associations between alterations of the MMR system and human fertility and related treatments, and potential effects on the next generation.

  7. Taphonomic alterations by the rodent species woodland vole (Microtus pinetorum) upon human skeletal remains.

    Science.gov (United States)

    Pokines, James T

    2015-12-01

    This forensic case report describes the taphonomic effects of woodland vole (Microtus pinetorum) upon a set of skeletonized human remains recovered in Massachusetts, USA. Remains of an individual of this rodent species were discovered where it had been nesting inside the human cranium. Fine, parallel grooves indicative of small rodent gnawing were noted on multiple postcranial elements, and all isolated grooves were consistent in size with the incisors of this species. Other taphonomic alterations to these remains include some gnawing damage and dispersal by large carnivores. This case represents the first report of this rodent species affecting human remains. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Influence of connectivity, wild prey and disturbance on occupancy of tigers in the human-dominated western Terai Arc Landscape.

    Science.gov (United States)

    Harihar, Abishek; Pandav, Bivash

    2012-01-01

    Occupying only 7% of their historical range and confined to forested habitats interspersed in a matrix of human dominated landscapes, tigers (Panthera tigris) typify the problems faced by most large carnivores worldwide. With heads of governments of tiger range countries pledging to reverse the extinction process and setting a goal of doubling wild tiger numbers by 2022, achieving this target would require identifying existing breeding cores, potential breeding habitats and opportunities for dispersal. The Terai Arc Landscape (TAL) represents one region which has recently witnessed recovery of tiger populations following conservation efforts. In this study, we develop a spatially explicit tiger occupancy model with survey data from 2009-10 based on a priori knowledge of tiger biology and specific issues plaguing the western TAL (6,979 km(2)), which occurs in two disjunct units (Tiger Habitat Blocks; THBs). Although the overall occupancy of tigers was 0.588 (SE 0.071), our results clearly indicate that loss in functionality of a regional corridor has resulted in tigers now occupying 17.58% of the available habitat in THB I in comparison to 88.5% in THB II. The current patterns of occupancy were best explained by models incorporating the interactive effect of habitat blocks (AIC w = 0.883) on wild prey availability (AIC w = 0.742) and anthropogenic disturbances (AIC w = 0.143). Our analysis has helped identify areas of high tiger occupancy both within and outside existing protected areas, which highlights the need for a unified control of the landscape under a single conservation unit with the primary focus of managing tigers and associated wildlife. Finally, in the light of global conservation targets and recent legislations in India, our study assumes significance as we identify opportunities to secure (e.g. THB II) and increase (e.g. THB I) tiger populations in the landscape.

  9. Influence of connectivity, wild prey and disturbance on occupancy of tigers in the human-dominated western Terai Arc Landscape.

    Directory of Open Access Journals (Sweden)

    Abishek Harihar

    Full Text Available Occupying only 7% of their historical range and confined to forested habitats interspersed in a matrix of human dominated landscapes, tigers (Panthera tigris typify the problems faced by most large carnivores worldwide. With heads of governments of tiger range countries pledging to reverse the extinction process and setting a goal of doubling wild tiger numbers by 2022, achieving this target would require identifying existing breeding cores, potential breeding habitats and opportunities for dispersal. The Terai Arc Landscape (TAL represents one region which has recently witnessed recovery of tiger populations following conservation efforts. In this study, we develop a spatially explicit tiger occupancy model with survey data from 2009-10 based on a priori knowledge of tiger biology and specific issues plaguing the western TAL (6,979 km(2, which occurs in two disjunct units (Tiger Habitat Blocks; THBs. Although the overall occupancy of tigers was 0.588 (SE 0.071, our results clearly indicate that loss in functionality of a regional corridor has resulted in tigers now occupying 17.58% of the available habitat in THB I in comparison to 88.5% in THB II. The current patterns of occupancy were best explained by models incorporating the interactive effect of habitat blocks (AIC w = 0.883 on wild prey availability (AIC w = 0.742 and anthropogenic disturbances (AIC w = 0.143. Our analysis has helped identify areas of high tiger occupancy both within and outside existing protected areas, which highlights the need for a unified control of the landscape under a single conservation unit with the primary focus of managing tigers and associated wildlife. Finally, in the light of global conservation targets and recent legislations in India, our study assumes significance as we identify opportunities to secure (e.g. THB II and increase (e.g. THB I tiger populations in the landscape.

  10. Reaction and fractal description of soil bio-indicator to human disturbance in lowland forests of Iran

    Directory of Open Access Journals (Sweden)

    SAKINEH MOLLAEI DARABI

    2014-04-01

    Full Text Available Mollaei-Darabi S, Kooch Y, Hosseini SM. 2014. Reaction and fractal description of soil bio-indicator to human disturbance in lowland forests of Iran. Biodiversitas 15: 58-64. Earthworms are expected to be good bio-indicators for forest site quality. The deforestation of land into another function could changes the soil features that could effect on earthworm population. This study was conducted to understand the changes of soil functions, resulting from exploitive management using some soil features and their fractal dimensions. Two sites were selected, consisting of an undisturbed forest site (FS and a completely deforested site (DS in lowland part of Khanikan forests located in Mazandaran province, north of Iran. Within each site 50 soil samples were obtained from 0-30cm depth along two sampling lines with 250 meter length for each. Deforestation brought a lower soil quality in the sites under the study. Decreasing silt, clay, moisture, pH, carbon to nitrogen ratio, available Ca, earthworm density and biomass, increasing bulk density and sand were few outcomes of the deforestation. Except for clay, the deforestation affect on fractal dimension of soil features. The fractal dimension of bulk density, silt, moisture, pH, earthworm density and biomass were decreased imposed by deforestation. Our results suggest that deforestation should be regarded as an effective factor on variability of soil features that are tied to forest ecology. This is significant for evaluating forest management policies and practices with respect to effects on soil and also for the use of soils as indicators, especially earthworms as bio-indicator, of forest ecosystems.

  11. Contemporary human-altered landscapes and oceanic barriers reduce bumble bee gene flow.

    Science.gov (United States)

    Jha, S

    2015-03-01

    Much of the world's terrestrial landscapes are being altered by humans in the form of agriculture, urbanization and pastoral systems, with major implications for biodiversity. Bumble bees are one of the most effective pollinators in both natural and cultivated landscapes, but are often the first to be extirpated in human-altered habitats. Yet, little is known about the role of natural and human-altered habitats in promoting or limiting bumble bee gene flow. In this study, I closely examine the genetic structure of the yellow-faced bumble bee, Bombus vosnesenskii, across the southwestern US coast and find strong evidence that natural oceanic barriers, as well as contemporary human-altered habitats, limit bee gene flow. Heterozygosity and allelic richness were lower in island populations, while private allelic richness was higher in island populations compared to mainland populations. Genetic differentiation, measured for three indices across the 1000 km study region, was significantly greater than the null expectation (F(ST) = 0.041, F'(ST) = 0.044 and D(est) = 0.155) and correlated with geographic distance. Furthermore, genetic differentiation patterns were most strongly correlated with contemporary (2011) not past (2006, 2001) resistance maps calibrated for high dispersal limitation over oceans, impervious habitat and croplands. Despite the incorporation of dramatic elevation gradients, the analyses reveal that oceans and contemporary human land use, not mountains, are the primary dispersal barriers for B. vosnesenskii gene flow. These findings reinforce the importance of maintaining corridors of suitable habitat across the distribution range of native pollinators to promote their persistence and safeguard their ability to provide essential pollination services.

  12. Human impact on the hydrology of the Lake of Monate (Italy): an experimental data base to investigate anthropogenic disturbance

    Science.gov (United States)

    Montanari, A.; Castellarin, A.

    2014-12-01

    , hydrological and ecological data base of the Lake of Monate to the scientific community and the first findings on the hydrology of the lake and the hydrological disturbance induced by the mining activities. The results show that particular care should be taken when estimating the human impact in catchments where groundwater flow is the main driver of hydrological fluxes.

  13. Comparative oncogenomic analysis of copy number alterations in human and zebrafish tumors enables cancer driver discovery.

    Directory of Open Access Journals (Sweden)

    GuangJun Zhang

    2013-08-01

    Full Text Available The identification of cancer drivers is a major goal of current cancer research. Finding driver genes within large chromosomal events is especially challenging because such alterations encompass many genes. Previously, we demonstrated that zebrafish malignant peripheral nerve sheath tumors (MPNSTs are highly aneuploid, much like human tumors. In this study, we examined 147 zebrafish MPNSTs by massively parallel sequencing and identified both large and focal copy number alterations (CNAs. Given the low degree of conserved synteny between fish and mammals, we reasoned that comparative analyses of CNAs from fish versus human MPNSTs would enable elimination of a large proportion of passenger mutations, especially on large CNAs. We established a list of orthologous genes between human and zebrafish, which includes approximately two-thirds of human protein-coding genes. For the subset of these genes found in human MPNST CNAs, only one quarter of their orthologues were co-gained or co-lost in zebrafish, dramatically narrowing the list of candidate cancer drivers for both focal and large CNAs. We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers.

  14. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  15. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging

    OpenAIRE

    Quan, Taihao; Fisher, Gary J.

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin d...

  16. Dibutyltin-induced alterations of interleukin 1beta secretion from human immune cells.

    Science.gov (United States)

    Brown, Shyretha; Tehrani, Shahin; Whalen, Margaret M

    2017-02-01

    Dibutyltin (DBT) is used to stabilize polyvinyl chloride plastics (including pipes that distribute drinking water) and as a de-worming agent in poultry. DBT is found in human blood, and DBT exposures alter the secretion of tumor necrosis factor alpha and interferon gamma from lymphocytes. Interleukin (IL)-1β is a proinflammatory cytokine that regulates cellular growth, tissue restoration and immune response regulation. IL-1β plays a role in increasing invasiveness of certain tumors. This study reveals that exposures to DBT (24 h, 48 h and 6 days) modify the secretion of IL-1β from increasingly reconstituted preparations of human immune cells (highly enriched human natural killer cells, monocyte-depleted [MD] peripheral blood mononuclear cells [PBMCs], PBMCs, granulocytes and a preparation combining both PBMCs and granulocytes). DBT altered IL-1β secretion from all cell preparations. Higher concentrations of DBT (5 and 2.5 μm) decreased the secretion of IL-1β, while lower concentrations of DBT (0.1 and 0.05 μm) increased the secretion of IL-1β. Selected signaling pathways were examined in MD-PBMCs to determine if they play a role in DBT-induced elevations of IL-1β secretion. Pathways examined were IL-1β converting enzyme (caspase 1), mitogen-activated protein kinases and nuclear factor kappa B. Caspase 1 and mitogen-activated protein kinase pathways appear to be utilized by DBT in increasing IL-1β secretion. These results indicate that DBT alters IL-1β secretion from human immune cells in an ex. vivo system utilizing several IL-1β regulating signaling pathways. Thus, DBT may have the potential to alter IL-1β secretion in an in vivo system. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Variability in the Structure of Phytoplankton Assemblages in relation to Human Disturbance in Southern Coast of Tunisia

    Directory of Open Access Journals (Sweden)

    Lotfi Mabrouk

    2014-01-01

    Full Text Available We investigated the impact of industrial effluents on phytoplankton assemblage in southern Tunisia (Skhira. We specifically addressed changes in microalgae composition caused by this anthropogenic interference. A hierarchical sampling design was used to compare planktonic microalgae structure between one disturbed station and one control station. Samples were collected by scuba diving at 5 m depth in August 2012. A total of 76 microalgae taxa were identified. Dinoflagellates abundance was low in the disturbed station, especially Gonyaulacales and Prorocentrales due to P-limitation, whereas diatoms and cyanobacteria abundance were low in control station which is characterized by Si-limitation.

  18. [Identification of ecological corridors for Tibetan antelope and assessment of their human disturbances in the alpine desert of Qinghai-Tibet Plateau].

    Science.gov (United States)

    Zhuge, Hai-jin; Lin, Dan-qi; Li, Xiao-wen

    2015-08-01

    The alpine desert of Qinghai-Tibet Plateau (QTP) provides the largest habitats for those endangered ungulates (e.g., Tibetan antelope, Tibetan Kiang and wild yak) on the earth. However, human disturbance especially infrastructure constructions (e.g., railway & highway) has increasingly fragmented the habitats of those endangered ungulates by disturbing and interrupting their ecological corridors for their seasonal migration. Aiming at identifying the potential ecological corridors for Tibetan antelope, a GIS-based model-Linkage Mapper was used to model and detect the potential ecological corridors of Tibetan antelope based on the principle of least cost path. Three categories of ecological corridors, i. e., closed (inside reserves), linking (linking the reserves) and open (starting from reserve but ending outside) corridors were distinguished by their spatial interactions with existing major national nature reserves (i.e., Altun, Kekexili and Qiangtang NNRs) in the alpine desert of QTP, and their spatial patterns, conservation status associated with human disturbance were also examined. Although our research indicated a general ecological integration of both habitats and ecological corridors in the alpine desert ecosystem, increasing human disturbance should not be ignored, which particularly partially undermined the functioning of those ecological corridors linking the nature reserves. Considering disadvantages of prevailing separate administrative structure of nature reserve on the effective conservation of ecological corridors for those endangered ungulates, a coordinative conservation network among these major national nature reserves should be established to ensure the unified trans-boundary conservation efforts and to enhance its overall conservation efficacy by sharing information, knowledge and optimizing conservation resources.

  19. Secretion of interferon gamma from human immune cells is altered by exposure to tributyltin and dibutyltin.

    Science.gov (United States)

    Lawrence, Shanieek; Reid, Jacqueline; Whalen, Margaret

    2015-05-01

    Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and alter secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro-inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion of IFNγ from human immune cells. Peripheral blood cell preparations that were increasingly reconstituted were used to determine if exposures to either TBT or DBT affected IFNγ secretion and how the makeup of the cell preparation influenced that effect. IFNγ secretion was examined after 24 h, 48 h, and 6 day exposures to TBT (200 - 2.5 nM) and DBT (5 - 0.05 µM) in highly enriched human NK cells, a monocyte-depleted preparation of PBMCs, and monocyte-containing PBMCs. Both BTs altered IFNγ secretion from immune cells at most of the conditions tested (either increasing or decreasing secretion). However, there was significant variability among donors as to the concentrations and time points that showed changes as well as the baseline secretion of IFNγ. The majority of donors showed an increase in IFNγ secretion in response to at least one concentration of TBT or DBT at a minimum of one length of exposure.

  20. Human trampling as short-term disturbance on intertidal mudflats: effects on macrofauna biodiversity and population dynamics of bivalves

    NARCIS (Netherlands)

    Rossi, F.; Forster, R.M.; Montserrat Trotsenburg, F.; Ponti, M.; Terlizzi, A.; Ysebaert, T.; Middelburg, J.J.

    2007-01-01

    The effect of physical disturbance in the form of trampling on the benthic environment of an intertidal mudflat was investigated. Intense trampling was created as unintended side-effect by benthic ecologists during field experiments in spring and summer 2005, when a mid-shore area of 25 × 25 m was

  1. Sleep disturbances in Parkinsonism.

    Science.gov (United States)

    Askenasy, J J M

    2003-02-01

    The present article is meant to suggest an approach to the guidelines for the therapy of sleep disturbances in Parkinson's Disease (PD) patients.The factors affecting the quality of life in PD patients are depression, sleep disturbances and dependence. A large review of the literature on sleep disturbances in PD patients, provided the basis for the following classification of the sleep-arousal disturbances in PD patients. We suggest a model based on 3 steps in the treatment of sleep disturbances in PD patients. This model allowing the patient, the spouse or the caregiver a quiet sleep at night, may postpone the retirement and the institutionalization of the PD patient. I. Correct diagnosis of sleep disorders based on detailed anamnesis of the patient and of the spouse or of the caregiver. One week recording on a symptom diary (log) by the patient or the caregiver. Correct diagnosis of sleep disorders co morbidities. Selection of the most appropriate sleep test among: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), Epworth Sleepiness Scale, actigraphy or video-PSG. II. The nonspecific therapeutic approach consists in: a) Checking the sleep effect on motor performance, is it beneficial, worse or neutral. b) Psycho-physical assistance. c) Dopaminergic adjustment is necessary owing to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals, which alter the normal modulator mechanisms of the motor centers in PD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and NonREM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates PD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. The permanent adjustment

  2. Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency.

    NARCIS (Netherlands)

    Schmidt, A.; Marescau, B.; Boehm, E.A.; Renema, W.K.J.; Peco, R.; Das, A.; Steinfeld, R.; Chan, S.; Wallis, J.; Davidoff, M.; Ullrich, K.; Waldschutz, R.; Heerschap, A.; Deyn, P.P. de; Neubauer, S.; Isbrandt, D.

    2004-01-01

    We generated a knockout mouse model for guanidinoacetate N-methyltransferase (GAMT) deficiency (MIM 601240), the first discovered human creatine deficiency syndrome, by gene targeting in embryonic stem cells. Disruption of the open reading frame of the murine GAMT gene in the first exon resulted in

  3. Resource selection of moose (Alces alces cameloides) and their response to human disturbances in the northwestern slope of Lesser Khingan Mountains, northeastern China

    Institute of Scientific and Technical Information of China (English)

    HU Su-xian; JIANG Guang-shun; MA Jian-zhang; ZHANG Ming-hai; LIU Hui

    2013-01-01

    Moose (Alces alces cameloides) is typically representative of the fauna of the frigid temperate zone and has been put on the Chinese second priority list of protected animals. The moose of northeast China is on the southern most edge of its distribution in Asia. To study resource selection characteristics of moose and their response to human distur-bances and forest resource variables, the field work was conducted in Heilongjiang Provincial Shengshan Forestry Farm, which is located in the northwestern slope of Lesser Khingan Mountains, northeastern China, from January to March in both 2006 and 2007. A total of 428 plots were examined within the study area. Signs of moose use were found in 19 plots. Based on the analysis of resource selection function, we found that moose selected areas with higher densities of mixed deciduous broadleaf patch and mixed coniferous and broad leaf patch, and a higher NDVI value. Moose avoided settlement 6 km away and remained low probability of occurrence within 3 km from roads, whereas higher within 4 km from trails. Our results suggested that the behavior of avoidance for human disturbance (i.e. settlement and roads) may indirectly pose habitat loss. Therefore, resource selection function models and corresponding graphs of important habitat disturbances can be used to guide and evaluate future development plans.

  4. Climate change and physical disturbance cause similar community shifts in biological soil crusts.

    Science.gov (United States)

    Ferrenberg, Scott; Reed, Sasha C; Belnap, Jayne

    2015-09-29

    Biological soil crusts (biocrusts)—communities of mosses, lichens, cyanobacteria, and heterotrophs living at the soil surface—are fundamental components of drylands worldwide, and destruction of biocrusts dramatically alters biogeochemical processes, hydrology, surface energy balance, and vegetation cover. Although there has been long-standing concern over impacts of physical disturbances on biocrusts (e.g., trampling by livestock, damage from vehicles), there is increasing concern over the potential for climate change to alter biocrust community structure. Using long-term data from the Colorado Plateau, we examined the effects of 10 y of experimental warming and altered precipitation (in full-factorial design) on biocrust communities and compared the effects of altered climate with those of long-term physical disturbance (>10 y of replicated human trampling). Surprisingly, altered climate and physical disturbance treatments had similar effects on biocrust community structure. Warming, altered precipitation frequency [an increase of small (1.2 mm) summer rainfall events], and physical disturbance from trampling all promoted early successional community states marked by dramatic declines in moss cover and increases in cyanobacteria cover, with more variable effects on lichens. Although the pace of community change varied significantly among treatments, our results suggest that multiple aspects of climate change will affect biocrusts to the same degree as physical disturbance. This is particularly disconcerting in the context of warming, as temperatures for drylands are projected to increase beyond those imposed as treatments in our study.

  5. Climate change and physical disturbance cause similar community shifts in biological soil crusts

    Science.gov (United States)

    Ferrenberg, Scott; Reed, Sasha C.; Belnap, Jayne

    2015-01-01

    Biological soil crusts (biocrusts)—communities of mosses, lichens, cyanobacteria, and heterotrophs living at the soil surface—are fundamental components of drylands worldwide, and destruction of biocrusts dramatically alters biogeochemical processes, hydrology, surface energy balance, and vegetation cover. While there has been long-standing concern over impacts of 5 physical disturbances on biocrusts (e.g., trampling by livestock, damage from vehicles), there is also increasing concern over the potential for climate change to alter biocrust community structure. Using long-term data from the Colorado Plateau, USA, we examined the effects of 10 years of experimental warming and altered precipitation (in full-factorial design) on biocrust communities, and compared the effects of altered climate with those of long-term physical 10 disturbance (>10 years of replicated human trampling). Surprisingly, altered climate and physical disturbance treatments had similar effects on biocrust community structure. Warming, altered precipitation frequency [an increase of small (1.2 mm) summer rainfall events], and physical disturbance from trampling all promoted early successional community states marked by dramatic declines in moss cover and increased cyanobacteria cover, with more variable effects 15 on lichens. While the pace of community change varied significantly among treatments, our results suggest that multiple aspects of climate change will affect biocrusts to the same degree as physical disturbance. This is particularly disconcerting in the context of warming, as temperatures for drylands are projected to increase beyond those imposed by the climate treatments used in our study.

  6. Short-term fasting alters cytochrome P450-mediated drug metabolism in humans.

    Science.gov (United States)

    Lammers, Laureen A; Achterbergh, Roos; de Vries, Emmely M; van Nierop, F Samuel; Klümpen, Heinz-Josef; Soeters, Maarten R; Boelen, Anita; Romijn, Johannes A; Mathôt, Ron A A

    2015-06-01

    Experimental studies indicate that short-term fasting alters drug metabolism. However, the effects of short-term fasting on drug metabolism in humans need further investigation. Therefore, the aim of this study was to evaluate the effects of short-term fasting (36 h) on P450-mediated drug metabolism. In a randomized crossover study design, nine healthy subjects ingested a cocktail consisting of five P450-specific probe drugs [caffeine (CYP1A2), S-warfarin (CYP2C9), omeprazole (CYP2C19), metoprolol (CYP2D6), and midazolam (CYP3A4)] on two occasions (control study after an overnight fast and after 36 h of fasting). Blood samples were drawn for pharmacokinetic analysis using nonlinear mixed effects modeling. In addition, we studied in Wistar rats the effects of short-term fasting on hepatic mRNA expression of P450 isoforms corresponding with the five studied P450 enzymes in humans. In the healthy subjects, short-term fasting increased oral caffeine clearance by 20% (P = 0.03) and decreased oral S-warfarin clearance by 25% (P fasting increased mRNA expression of the orthologs of human CYP1A2, CYP2C19, CYP2D6, and CYP3A4 (P fasting alters cytochrome P450-mediated drug metabolism in a nonuniform pattern. Therefore, short-term fasting is another factor affecting cytochrome P450-mediated drug metabolism in humans.

  7. Investigation of alterations in multifractality in optical coherence tomographic images of in vivo human retina

    Science.gov (United States)

    Das, Nandan Kumar; Mukhopadhyay, Sabyasachi; Ghosh, Nirmalya; Chhablani, Jay; Richhariya, Ashutosh; Divakar Rao, Kompalli; Sahoo, Naba Kishore

    2016-09-01

    Optical coherence tomography (OCT) enables us to monitor alterations in the thickness of the retinal layer as disease progresses in the human retina. However, subtle morphological changes in the retinal layers due to early disease progression often may not lead to detectable alterations in the thickness. OCT images encode depth-dependent backscattered intensity distribution arising due to the depth distributions of the refractive index from tissue microstructures. Here, such depth-resolved refractive index variations of different retinal layers were analyzed using multifractal detrended fluctuation analysis, a special class of multiresolution analysis tools. The analysis extracted and quantified microstructural multifractal information encoded in normal as well as diseased human retinal OCT images acquired in vivo. Interestingly, different layers of the retina exhibited different degrees of multifractality in a particular retina, and the individual layers displayed consistent multifractal trends in healthy retinas of different human subjects. In the retinal layers of diabetic macular edema (DME) subjects, the change in multifractality manifested prominently near the boundary of the DME as compared to the normal retinal layers. The demonstrated ability to quantify depth-resolved information on multifractality encoded in OCT images appears promising for the early diagnosis of diseases of the human eye, which may also prove useful for detecting other types of tissue abnormalities from OCT images.

  8. Transforming growth factor-β2 induces morphological alteration of human corneal endothelial cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Jing; Wang; Ting-Jun; Fan; Xiu-Xia; Yang; Shi-Min; Chang

    2014-01-01

    AIM:To investigate the morphological altering effect of transforming growth factor-β2(TGF-β2) on untransfected human corneal endothelial cells(HCECs)in vitro.METHODS:After untransfected HCECs were treated with TGF-β2 at different concentrations, the morphology,cytoskeleton distribution, and type IV collagen expression of the cells were examined with inverted contrast light microscopy, fluorescence microscopy,immunofluorescence or Western Blot.RESULTS:TGF-β2 at the concentration of 3-15 μg/L had obviously alterative effects on HCECs morphology in dose and time-dependent manner, and 9 μg/L was the peak concentration. TGF-β2(9 μg/L) altered HCE cell morphology after treatment for 36 h, increased the mean optical density(P <0.01) and the length of F-actin,reduced the mean optical density(P <0.01) of the collagen type IV in extracellular matrix(ECM) and induced the rearrangement of F-actin, microtubule in cytoplasm and collagen type IV in ECM after treatment for 72 h.·CONCLUTION: TGF-β2 has obviously alterative effect on the morphology of HCECs from polygonal phenotype to enlarged spindle-shaped phenotype, in dose and time-dependence manner by inducing more, elongation and alignment of F-actin, rearrangement of microtubule and larger spread area of collagen type IV.

  9. Culture of human adipose tissue explants leads to profound alteration of adipocyte gene expression.

    Science.gov (United States)

    Gesta, S; Lolmède, K; Daviaud, D; Berlan, M; Bouloumié, A; Lafontan, M; Valet, P; Saulnier-Blache, J S

    2003-03-01

    Primary culture of adipose tissue has often been used to investigate pharmacological and nutritional regulation of adipocyte gene expression. Possible alteration of adipocyte gene expression by primary culture on its own has not been explored in detail. In order to address this issue, explants were prepared from human subcutaneous adipose tissue recovered from plastic surgery and maintained for 0 to 48 h in DMEM supplemented with 10 % serum. At different time points, adipocytes were isolated from the explants by collagenase digestion, and mRNA expression and lipolysis were studied. Culture was associated with an accumulation of tumor necrosis factor-alpha (TNFalpha) in the culture medium, an increase in anaerobic glycolysis, and an increase in the basal lipolysis. In parallel, a rapid and dramatic decrease in the level of mRNA encoding for several adipocyte-specific proteins such as adipocyte lipid-binding protein, hormone-sensitive lipase, lipoprotein lipase, and peroxisome proliferation activating receptor-gamma2 was observed in isolated adipocytes. These downregulations were reminiscent of a dedifferentiation process. In parallel, primary culture was associated with an increase in adipocyte beta-actin, TNFalpha, glucose transporter-1 and hypoxia-induced factor-1alpha mRNAs. Treatment of explants with agents that increase cAMP (isobutylmethylxanthine and forskolin) prevented TNFalpha production and expression and culture-induced alterations of adipocyte gene expression. These data show that primary culture of human adipose tissue explants dramatically alters adipocyte gene expression.

  10. Human liver epigenetic alterations in non-alcoholic steatohepatitis are related to insulin action.

    Science.gov (United States)

    de Mello, Vanessa D; Matte, Ashok; Perfilyev, Alexander; Männistö, Ville; Rönn, Tina; Nilsson, Emma; Käkelä, Pirjo; Ling, Charlotte; Pihlajamäki, Jussi

    2017-04-03

    Both genetic and lifestyle factors contribute to the risk of non-alcoholic steatohepatitis (NASH). Additionally, epigenetic modifications may also play a key role in the pathogenesis of NASH. We therefore investigated liver DNA methylation, as a marker for epigenetic alterations, in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. Liver biopsies obtained from 95 obese individuals (age: 49.5 ± 7.7 years, BMI: 43 ± 5.7 kg/m(2), type 2 diabetes [T2D]: 35) as a wedge biopsy during a Roux-en-Y gastric bypass operation were investigated. Thirty-four individuals had a normal liver phenotype, 35 had simple steatosis, and 26 had NASH. Genome-wide DNA methylation pattern was analyzed using the Infinium HumanMethylation450 BeadChip. mRNA expression was analyzed from 42 individuals using the HumanHT-12 Expression BeadChip. We identified 1,292 CpG sites representing 677 unique genes differentially methylated in liver of individuals with NASH (q liver. These epigenetic alterations in NASH are linked with insulin metabolism.

  11. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER FLASH OR PATTERN REVERSAL EVOKED POTENTIALS IN RATS.

    Science.gov (United States)

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Visual disturbances are often reported following exposure to xenobiotics, and cholinesterase-inhibiting compounds have been reported to alter visual functi...

  12. Accounting for regional variation in both natural environment and human disturbance to improve performance of multimetric indices of lotic benthic diatoms.

    Science.gov (United States)

    Tang, Tao; Stevenson, R Jan; Infante, Dana M

    2016-10-15

    Regional variation in both natural environment and human disturbance can influence performance of ecological assessments. In this study we calculated 5 types of benthic diatom multimetric indices (MMIs) with 3 different approaches to account for variation in ecological assessments. We used: site groups defined by ecoregions or diatom typologies; the same or different sets of metrics among site groups; and unmodeled or modeled MMIs, where models accounted for natural variation in metrics within site groups by calculating an expected reference condition for each metric and each site. We used data from the USEPA's National Rivers and Streams Assessment to calculate the MMIs and evaluate changes in MMI performance. MMI performance was evaluated with indices of precision, bias, responsiveness, sensitivity and relevancy which were respectively measured as MMI variation among reference sites, effects of natural variables on MMIs, difference between MMIs at reference and highly disturbed sites, percent of highly disturbed sites properly classified, and relation of MMIs to human disturbance and stressors. All 5 types of MMIs showed considerable discrimination ability. Using different metrics among ecoregions sometimes reduced precision, but it consistently increased responsiveness, sensitivity, and relevancy. Site specific metric modeling reduced bias and increased responsiveness. Combined use of different metrics among site groups and site specific modeling significantly improved MMI performance irrespective of site grouping approach. Compared to ecoregion site classification, grouping sites based on diatom typologies improved precision, but did not improve overall performance of MMIs if we accounted for natural variation in metrics with site specific models. We conclude that using different metrics among ecoregions and site specific metric modeling improve MMI performance, particularly when used together. Applications of these MMI approaches in ecological assessments

  13. Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome.

    Science.gov (United States)

    Monaco, Cynthia L; Gootenberg, David B; Zhao, Guoyan; Handley, Scott A; Ghebremichael, Musie S; Lim, Efrem S; Lankowski, Alex; Baldridge, Megan T; Wilen, Craig B; Flagg, Meaghan; Norman, Jason M; Keller, Brian C; Luévano, Jesús Mario; Wang, David; Boum, Yap; Martin, Jeffrey N; Hunt, Peter W; Bangsberg, David R; Siedner, Mark J; Kwon, Douglas S; Virgin, Herbert W

    2016-03-09

    Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression.

  14. Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis.

    Science.gov (United States)

    Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L; Zhang, Yuxi; Chen, Li; Postert, Benno; Parsons, Stuart; Ditzel, Nicholas; Khosla, Sundeep; Johansen, Harald Thidemann; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie; Abdallah, Basem M; Hesselson, Daniel; Solberg, Rigmor; Kassem, Moustapha

    2017-02-14

    Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

  15. Effects of climate change and anthropogenic modification on a disturbance-dependent species in a large riverine system

    Science.gov (United States)

    Zeigler, Sara; Catlin, Daniel H.; Bomberger Brown, M.; Fraser, J.D.; Dinan, Lauren R.; Hunt, Kelsi L.; Jorgensen, Joel G.; Karpanty, Sarah M.

    2017-01-01

    Humans have altered nearly every natural disturbance regime on the planet through climate and land-use change, and in many instances, these processes may have interacting effects. For example, projected shifts in temperature and precipitation will likely influence disturbance regimes already affected by anthropogenic fire suppression or river impoundments. Understanding how disturbance-dependent species respond to complex and interacting environmental changes is important for conservation efforts. Using field-based demographic and movement rates, we conducted a metapopulation viability analysis for piping plovers (Charadrius melodus), a threatened disturbance-dependent species, along the Missouri and Platte rivers in the Great Plains of North America. Our aim was to better understand current and projected future metapopulation dynamics given that natural disturbances (flooding or high-flow events) have been greatly reduced by river impoundments and that climate change could further alter the disturbance regime. Although metapopulation abundance has been substantially reduced under the current suppressed disturbance regime (high-flow return interval ~ 20 yr), it could grow if the frequency of high-flow events increases as predicted under likely climate change scenarios. We found that a four-year return interval would maximize metapopulation abundance, and all subpopulations in the metapopulation would act as sources at a return interval of 15 yr or less. Regardless of disturbance frequency, the presence of even a small, stable source subpopulation buffered the metapopulation and sustained a low metapopulation extinction risk. Therefore, climate change could have positive effects in ecosystems where disturbances have been anthropogenically suppressed when climatic shifts move disturbance regimes toward more historical patterns. Furthermore, stable source populations, even if unintentionally maintained through anthropogenic activities, may be critical for the

  16. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review.

    Science.gov (United States)

    Chappell, Grace; Pogribny, Igor P; Guyton, Kathryn Z; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function.

    Science.gov (United States)

    Sunitha, Balaraju; Gayathri, Narayanappa; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Nalini, Atchayaram; Padmanabhan, Balasundaram; Srinivas Bharath, Muchukunte Mukunda

    2016-07-01

    Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies

  18. Changes of Dietary Fat and Carbohydrate Content Alter Central and Peripheral Clock in Humans.

    Science.gov (United States)

    Pivovarova, Olga; Jürchott, Karsten; Rudovich, Natalia; Hornemann, Silke; Ye, Lu; Möckel, Simona; Murahovschi, Veronica; Kessler, Katharina; Seltmann, Anne-Cathrin; Maser-Gluth, Christiane; Mazuch, Jeannine; Kruse, Michael; Busjahn, Andreas; Kramer, Achim; Pfeiffer, Andreas F H

    2015-06-01

    The circadian clock coordinates numerous metabolic processes with light-dark and feeding regimens. However, in humans it is unknown whether dietary patterns influence circadian rhythms. We examined the effects of switching from a high-carbohydrate, low-fat diet to a low-carbohydrate, high fat (LC/HFD) isocaloric diet on the central and peripheral circadian clocks in humans. Diurnal patterns of salivary cortisol and gene expression were analyzed in blood monocytes of 29 nonobese healthy subjects before and 1 and 6 weeks after the dietary switch. For this, we established a method of rhythm prediction by 3-time point data. The centrally driven cortisol rhythm showed a phase delay 1 and 6 weeks after the dietary switch to a LC/HFD as well as an amplitude increase. The dietary switch altered diurnal oscillations of core clock genes (PER1, PER2, PER3, and TEF) and inflammatory genes (CD14, CD180, NFKBIA, and IL1B). The LC/HFD also affected the expression of nonoscillating genes contributing to energy metabolism (SIRT1) and fat metabolism (ACOX3 and IDH3A). Expression of clock genes but not of salivary cortisol in monocytes tightly correlated with levels of blood lipids and with expression of metabolic and inflammatory genes. Our results suggest that the modulation of the dietary fat and carbohydrate content alters the function of the central and peripheral circadian clocks in humans.

  19. Simulation of landscape disturbances and the effect of climatic change

    Energy Technology Data Exchange (ETDEWEB)

    Baker, W.L.

    1993-04-01

    Altering the natural disturbance regime of a landscape produces changes in the structure of that landscape as the landscape adjusts to the new disturbance regime. A computer simulation model was designed to enable analyses of the longterm changes to be expected in landscapes as their disturbance regime changes. The model, DISPATCH, is the first dynamic spatial simulation model built around a geographical information system (GIS). The model also includes a new set of programs, the r.le programs, that is the first set of programs designed for calculating landscape structure measures within a GIS. The DISPATCH model was used, to analyze the effects of human alterations of disturbance regimes and global change on landscape structure. Landscapes do not adjust quickly to these alterations based on available data. Landscapes subjected to warming or to longterm fire suppression experience a decline in patch richness, Shannon diversity, the amount of edge and contrast, but an increase in distance between patches, angular second moment (texture measure) and patch size. In contrast, landscapes subjected to cooling, the short-term effects of fire suppression, fragmentation, or traditional prescribed burning tend to respond with increasing richness, Shannon diversity, edge, and contrast, but declining distance, angular second moment, and size. The pattern of response is different at different scales, with important implications for species.

  20. Cross-cancer profiling of molecular alterations within the human autophagy interaction network.

    Science.gov (United States)

    Lebovitz, Chandra B; Robertson, A Gordon; Goya, Rodrigo; Jones, Steven J; Morin, Ryan D; Marra, Marco A; Gorski, Sharon M

    2015-01-01

    Aberrant activation or disruption of autophagy promotes tumorigenesis in various preclinical models of cancer, but whether the autophagy pathway is a target for recurrent molecular alteration in human cancer patient samples is unknown. To address this outstanding question, we surveyed 211 human autophagy-associated genes for tumor-related alterations to DNA sequence and RNA expression levels and examined their association with patient survival outcomes in multiple cancer types with sequence data from The Cancer Genome Atlas consortium. We found 3 (RB1CC1/FIP200, ULK4, WDR45/WIPI4) and one (ATG7) core autophagy genes to be under positive selection for somatic mutations in endometrial carcinoma and clear cell renal carcinoma, respectively, while 29 autophagy regulators and pathway interactors, including previously identified KEAP1, NFE2L2, and MTOR, were significantly mutated in 6 of the 11 cancer types examined. Gene expression analyses revealed that GABARAPL1 and MAP1LC3C/LC3C transcripts were less abundant in breast cancer and non-small cell lung cancers than in matched normal tissue controls; ATG4D transcripts were increased in lung squamous cell carcinoma, as were ATG16L2 transcripts in kidney cancer. Unsupervised clustering of autophagy-associated mRNA levels in tumors stratified patient overall survival in 3 of 9 cancer types (acute myeloid leukemia, clear cell renal carcinoma, and head and neck cancer). These analyses provide the first comprehensive resource of recurrently altered autophagy-associated genes in human tumors, and highlight cancer types and subtypes where perturbed autophagy may be relevant to patient overall survival.

  1. Analysis of cell surface alterations in Legionella pneumophila cells treated with human apolipoprotein E.

    Science.gov (United States)

    Palusinska-Szysz, Marta; Zdybicka-Barabas, Agnieszka; Cytryńska, Małgorzata; Wdowiak-Wróbel, Sylwia; Chmiel, Elżbieta; Gruszecki, Wiesław I

    2015-03-01

    Binding of human apolipoprotein E (apoE) to Legionella pneumophila lipopolysaccharide was analysed at the molecular level by Fourier-transform infrared spectroscopy, thereby providing biophysical evidence for apoE-L. pneumophila lipopolysaccharide interaction. Atomic force microscopy imaging of apoE-exposed L. pneumophila cells revealed alterations in the bacterial cell surface topography and nanomechanical properties in comparison with control bacteria. The changes induced by apoE binding to lipopolysaccharide on the surface of L. pneumophila cells may participate in: (1) impeding the penetration of host cells by the bacteria; (2) suppression of pathogen intracellular growth and eventually; and (3) inhibition of the development of infection.

  2. Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Jan Šilhavý

    Full Text Available Inflammation and oxidative stress have been implicated in the pathogenesis of metabolic disturbances. Esters of fumaric acid, mainly dimethyl fumarate, exhibit immunomodulatory, anti-inflammatory, and anti-oxidative effects. In the current study, we tested the hypothesis that fumaric acid ester (FAE treatment of an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP, will ameliorate inflammation, oxidative stress, and metabolic disturbances. We studied the effects of FAE treatment by administering Fumaderm, 10 mg/kg body weight for 4 weeks, to male SHR-CRP. Untreated male SHR-CRP rats were used as controls. All rats were fed a high sucrose diet. Compared to untreated controls, rats treated with FAE showed significantly lower levels of endogenous CRP but not transgenic human CRP, and amelioration of inflammation (reduced levels of serum IL6 and TNFα and oxidative stress (reduced levels of lipoperoxidation products in liver, heart, kidney, and plasma. FAE treatment was also associated with lower visceral fat weight and less ectopic fat accumulation in liver and muscle, greater levels of lipolysis, and greater incorporation of glucose into adipose tissue lipids. Analysis of gene expression profiles in the liver with Affymetrix arrays revealed that FAE treatment was associated with differential expression of genes in pathways that involve the regulation of inflammation and oxidative stress. These findings suggest potentially important anti-inflammatory, anti-oxidative, and metabolic effects of FAE in a model of inflammation and metabolic disturbances induced by human CRP.

  3. Resilience, rapid transitions and regime shifts: fingerprinting the responses of Lake Żabińskie (NE Poland) to climate variability and human disturbance since 1000 AD

    Science.gov (United States)

    Tylmann, Wojciech; Hernández-Almeida, Iván; Grosjean, Martin; José Gómez Navarro, Juan; Larocque-Tobler, Isabelle; Bonk, Alicja; Enters, Dirk; Ustrzycka, Alicja; Piotrowska, Natalia; Przybylak, Rajmund; Wacnik, Agnieszka; Witak, Małgorzata

    2016-04-01

    Rapid ecosystem transitions and adverse effects on ecosystem services as responses to combined climate and human impacts are of major concern. Yet few quantitative observational data exist, particularly for ecosystems that have a long history of human intervention. Here, we combine quantitative summer and winter climate reconstructions, climate model simulations and proxies for three major environmental pressures (land use, nutrients and erosion) to explore the system dynamics, resilience, and the role of disturbance regimes in varved eutrophic Lake Żabińskie since AD 1000. Comparison between regional and global climate simulations and quantitative climate reconstructions indicate that proxy data capture noticeably natural forced climate variability, while internal variability appears as the dominant source of climate variability in the climate model simulations during most parts of the last millennium. Using different multivariate analyses and change point detection techniques, we identify ecosystem changes through time and shifts between rather stable states and highly variable ones, as expressed by the proxies for land-use, erosion and productivity in the lake. Prior to AD 1600, the lake ecosystem was characterized by a high stability and resilience against considerable observed natural climate variability. In contrast, lake-ecosystem conditions started to fluctuate at high frequency across a broad range of states after AD 1600. The period AD 1748-1868 represents the phase with the strongest human disturbance of the ecosystem. Analyses of the frequency of change points in the multi-proxy dataset suggests that the last 400 years were highly variable and flickering with increasing vulnerability of the ecosystem to the combined effects of climate variability and anthropogenic disturbances. This led to significant rapid ecosystem transformations.

  4. Effects of human disturbance on a burrow nesting seabird Efectos de la presencia de humanos en aves marinas que anidan en madrigueras

    Directory of Open Access Journals (Sweden)

    Yuri V. Albores-Barajas

    2011-12-01

    Full Text Available During 2004, we followed 72 natural burrows to determine the effects of disturbance on breeding success of Cassin's auklets (Ptychoramphus aleuticus. We used distance from a human settlement or path in the analysis of disturbance. Birds whose burrows were closer to the path or the village had a higher rate of nest abandonment and lower breeding success compared to birds nesting further away from the path or the village. Also, older and more experienced individuals represented a larger proportion of the breeding population on less disturbed areas than on highly disturbed ones, probably as older individuals tend to arrive earlier at the breeding grounds, and failed breeders may change burrow sites to move away from disturbance. P. aleuticus are adversely affected by human activity at colonies even if birds are not handled and burrows are not opened, and this has implications for conservation, and planning of ecotourism. On the long term, this can have negative consequences for this species and others with similar characteristics.Durante el 2004 seguimos 72 nidos de la alcuela (Ptychoramphus aleuticus para determinar los efectos de disturbio en el éxito reproductivo. Utilizamos la distancia del nido a áreas asentamientos humanos o al camino como medidas de disturbio. Los nidos que estaban más cerca de los asentamientos o del camino tuvieron una tasa de abandono mayor y un éxito reproductivo menor en comparación con los nidos que estaban más alejados de las fuentes de disturbio. También observamos que en las zonas menos expuestas la proporción de adultos, con mayor experiencia, era más alta, posiblemente porque los individuos con mayor experiencia llegan antes a la zona de anidación. Las alcuelas son afectadas negativamente por la presencia de los humanos y sus actividades, aunque las aves no entren en contacto directo con los humanos. A largo plazo, esto puede acarrear consecuencias graves para esta especie y otras con caracter

  5. Alterations in tumour suppressor gene p53 in human gliomas from Indian patients

    Indian Academy of Sciences (India)

    Pornima Phatak; S Kalai Selvi; T Divya; A S Hegde; Sridevi Hegde; Kumaravel Somasundaram

    2002-12-01

    Alterations in the tumour suppressor p53 gene are among the most common defects seen in a variety of human cancers. In order to study the significance of the p53 gene in the genesis and development of human glioma from Indian patients, we checked 44 untreated primary gliomas for mutations in exons 5–9 of the p53 gene by PCR-SSCP and DNA sequencing. Sequencing analysis revealed six missense mutations. The incidence of p53 mutations was 13.6% (6 of 44). All the six mutations were found to be located in the central core domain of p53, which carries the sequence-specific DNA-binding domain. These results suggest a rather low incidence but a definite involvement of p53 mutations in the gliomas of Indian patients.

  6. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging

    Science.gov (United States)

    Quan, Taihao; Fisher, Gary J

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment (AADM), which contributes to decline of human skin function. PMID:25660807

  7. Human cytomegalovirus induces alteration of (-actin mRNA and microfilaments in human embryo fibroblast cells

    Institute of Scientific and Technical Information of China (English)

    林茂芳; 魏国庆; 黄河; 蔡真

    2004-01-01

    Objective: To investigate the infection of human embryo fibroblast cell line HF cells by CMV as well as the effects of CMV on β-actin mRNA and microfilaments. Methods: HF cells shape was observed after the infection of CMV. RT-PCR assay was used to detect the mRNA expression of CMV immediate early (IE) gene, β-actin and GAPDH genes of HF cells infected by CMV. CMV particles and cell microfilaments were detected with electron microscope. Results: Shape of HF cell changed after the infection by CMV. HF cells infected by CMV could express IE mRNA and the expression of β-actin mRNA decreased in a time- and titer-dependent manner compared with the uninfected HF cells whose expression of GAPDH mRNA did not change much. CMV particles were found with electron microscope in the cells. Microfilaments were ruptured and shortened after the infection of CMV. Conclusion: CMV can not only infect human embryo fibroblast cells line HF cells and replicate in the cells, but can also affect the expression of β-actin mRNA and the microfilaments.

  8. Remote sensing captures varying temporal patterns of vegetation between human-altered and natural landscapes.

    Science.gov (United States)

    Leong, Misha; Roderick, George K

    2015-01-01

    Global change has led to shifts in phenology, potentially disrupting species interactions such as plant-pollinator relationships. Advances in remote sensing techniques allow one to detect vegetation phenological diversity between different land use types, but it is not clear how this translates to other communities in the ecosystem. Here, we investigated the phenological diversity of the vegetation across a human-altered landscape including urban, agricultural, and natural land use types. We found that the patterns of change in the vegetation indices (EVI and NDVI) of human-altered landscapes are out of synchronization with the phenology in neighboring natural California grassland habitat. Comparing these findings to a spatio-temporal pollinator distribution dataset, EVI and NDVI were significant predictors of total bee abundance, a relationship that improved with time lags. This evidence supports the importance of differences in temporal dynamics between land use types. These findings also highlight the potential to utilize remote sensing data to make predictions for components of biodiversity that have tight vegetation associations, such as pollinators.

  9. Remote sensing captures varying temporal patterns of vegetation between human-altered and natural landscapes

    Directory of Open Access Journals (Sweden)

    Misha Leong

    2015-08-01

    Full Text Available Global change has led to shifts in phenology, potentially disrupting species interactions such as plant–pollinator relationships. Advances in remote sensing techniques allow one to detect vegetation phenological diversity between different land use types, but it is not clear how this translates to other communities in the ecosystem. Here, we investigated the phenological diversity of the vegetation across a human-altered landscape including urban, agricultural, and natural land use types. We found that the patterns of change in the vegetation indices (EVI and NDVI of human-altered landscapes are out of synchronization with the phenology in neighboring natural California grassland habitat. Comparing these findings to a spatio-temporal pollinator distribution dataset, EVI and NDVI were significant predictors of total bee abundance, a relationship that improved with time lags. This evidence supports the importance of differences in temporal dynamics between land use types. These findings also highlight the potential to utilize remote sensing data to make predictions for components of biodiversity that have tight vegetation associations, such as pollinators.

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

    Science.gov (United States)

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

    2014-11-11

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

  11. Morphological alteration of the Dráva as the result of human impact

    Directory of Open Access Journals (Sweden)

    Tímea Kiss

    2011-10-01

    Full Text Available The Croatian-Hungarian border section of the Dráva River has been undisturbed for almost a century, and it is characterised by unique fluvial morphology (braided pattern and islands supporting rich habitats and wildlife. However, during the last decades human impact became more and moreintensive. Between 1975 and 1989 three water reservoirs were built on the Croatian section of the river, just 16 km from the beginning of the border-section, altering the hydrology and the sediment characteristics of the river. On a local scale cut-offs, revetments and groynes were built. The aim of the study was to evaluate the effect of these human interventions. As the result of the alteration of the hydrology the channel pattern of the Dráva has been changing from braided to meandering, though on the upstream meandering part the territory and number of islands increased due to the drop of water stages. A cut-off and a groyne influenced only the morphology of a short section. As the result of the cut-off braided pattern became more pronounced, and the groyne caused intensive channel aggradation and gave way to lateral island development.

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

    Directory of Open Access Journals (Sweden)

    Ashwin Swaminathan

    2014-11-01

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

  13. Signal Transduction in Primary Human T Lymphocytes in Altered Gravity During Parabolic Flight and Clinostat Experiments

    Directory of Open Access Journals (Sweden)

    Svantje Tauber

    2015-02-01

    Full Text Available Background/Aims: Several limiting factors for human health and performance in microgravity have been clearly identified arising from the immune system, and substantial research activities are required in order to provide the basic information for appropriate integrated risk management. The gravity-sensitive nature of cells of the immune system renders them an ideal biological model in search for general gravity-sensitive mechanisms and to understand how the architecture and function of human cells is related to the gravitational force and therefore adapted to life on Earth. Methods: We investigated the influence of altered gravity in parabolic flight and 2D clinostat experiments on key proteins of activation and signaling in primary T lymphocytes. We quantified components of the signaling cascade 1. in non-activated T lymphocytes to assess the “basal status” of the cascade and 2. in the process of activation to assess the signal transduction. Results: We found a rapid decrease of CD3 and IL-2R surface expression and reduced p-LAT after 20 seconds of altered gravity in non-activated primary T lymphocytes during parabolic flight. Furthermore, we observed decreased CD3 surface expression, reduced ZAP-70 abundance and increased histone H3-acetylation in activated T lymphocytes after 5 minutes of clinorotation and a transient downregulation of CD3 and stable downregulation of IL-2R during 60 minutes of clinorotation. Conclusion: CD3 and IL-2R are downregulated in primary T lymphocytes in altered gravity. We assume that a gravity condition around 1g is required for the expression of key surface receptors and appropriate regulation of signal molecules in T lymphocytes.

  14. Platelet Activation in Human Immunodeficiency Virus Type-1 Patients Is Not Altered with Cocaine Abuse.

    Directory of Open Access Journals (Sweden)

    Michelle Kiebala

    Full Text Available Recent work has indicated that platelets, which are anucleate blood cells, significantly contribute to inflammatory disorders. Importantly, platelets also likely contribute to various inflammatory secondary disorders that are increasingly associated with Human Immunodeficiency Virus Type-1 (HIV infection including neurological impairments and cardiovascular complications. Indeed, HIV infection is often associated with increased levels of platelet activators. Additionally, cocaine, a drug commonly abused by HIV-infected individuals, leads to increased platelet activation in humans. Considering that orchestrated signaling mechanisms are essential for platelet activation, and that nuclear factor-kappa B (NF-κB inhibitors can alter platelet function, the role of NF-κB signaling in platelet activation during HIV infection warrants further investigation. Here we tested the hypothesis that inhibitory kappa B kinase complex (IKK activation would be central for platelet activation induced by HIV and cocaine. Whole blood from HIV-positive and HIV-negative individuals, with or without cocaine abuse was used to assess platelet activation via flow cytometry whereas IKK activation was analyzed by performing immunoblotting and in vitro kinase assays. We demonstrate that increased platelet activation in HIV patients, as measured by CD62P expression, is not altered with reported cocaine use. Furthermore, cocaine and HIV do not activate platelets in whole blood when treated ex vivo. Finally, HIV-induced platelet activation does not involve the NF-κB signaling intermediate, IKKβ. Platelet activation in HIV patients is not altered with cocaine abuse. These results support the notion that non-IKK targeting approaches will be better suited for the treatment of HIV-associated inflammatory disorders.

  15. Carbon dynamics of river corridors and the effects of human alterations

    Science.gov (United States)

    Wohl, Ellen; Hall, Robert O.; Lininger, Katherine B; Sutfin, Nicholas A.; Walters, David

    2017-01-01

    Research in stream metabolism, gas exchange, and sediment dynamics indicates that rivers are an active component of the global carbon cycle and that river form and process can influence partitioning of terrestrially derived carbon among the atmosphere, geosphere, and ocean. Here we develop a conceptual model of carbon dynamics (inputs, outputs, and storage of organic carbon) within a river corridor, which includes the active channel and the riparian zone. The exchange of carbon from the channel to the riparian zone represents potential for storage of transported carbon not included in the “active pipe” model of organic carbon (OC) dynamics in freshwater systems. The active pipe model recognizes that river processes influence carbon dynamics, but focuses on CO2 emissions from the channel and eventual delivery to the ocean. We also review how human activities directly and indirectly alter carbon dynamics within river corridors. We propose that dams create the most significant alteration of carbon dynamics within a channel, but that alteration of riparian zones, including the reduction of lateral connectivity between the channel and riparian zone, constitutes the most substantial change of carbon dynamics in river corridors. We argue that the morphology and processes of a river corridor regulate the ability to store, transform, and transport OC, and that people are pervasive modifiers of river morphology and processes. The net effect of most human activities, with the notable exception of reservoir construction, appears to be that of reducing the ability of river corridors to store OC within biota and sediment, which effectively converts river corridors to OC sources rather than OC sinks. We conclude by summarizing knowledge gaps in OC dynamics and the implications of our findings for managing OC dynamics within river corridors.

  16. Alterations of FHIT Gene and P16 Gene in Nickel Transformed Human Bronchial Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    WEI-DONG JI; JIA-KUN CHEN; JIA-CHUN LU; ZHONG-LIANG WU; FEI YI; SU-MEI FENG

    2006-01-01

    To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immoral human bronchial epithelial cell line, and to explore the molecular mechanism of nickel carcinogenesis. Methods 16HBE cells were treated 6 times with different concentrations of NiS in vitro, and the degree of malignant transformation was determined by assaying the anchorage-independent growth and tumorigenicity. Malignant transformed cells and tumorigenic cells were examined for alterations of FHIT gene and P16 gene using RT-PCR, DNA sequencing, silver staining PCR-SSCP and Western blotting. Results NiS-treated cells exhibited overlapping growth. Compared with that of negative control cells, soft agar colony formation efficiency of NiS-treated cells showed significant increases (P<0.01) and dose-dependent effects. NiS-treated cells could form tumors in nude mice, and a squamous cell carcinoma was confirmed by histopathological examination. No mutation of exon 2 and exons 2-3, no abnormal expression in p16 gene and mutation of FHIT exons 5-8 and exons 1-4 or exons 5-9 were observed in transformed cells and tumorigenic cells. However, aberrant transcripts or loss of expression of the FHIT gene and Fhit protein was observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in the FHIT gene was confirmed to have a deletion of exon 6, exon 7, exon 8, and an insertion of a 36 bp sequence replacing exon 6-8. Conclusions The FHIT gene rather than the P16 gene, plays a definite role in nickel carcinogenesis. Alterations of the FHIT gene induced by crystalline NiS may be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation. FHIT may be an important target gene activated by nickel and other exotic carcinogens.

  17. Signal transduction in primary human T lymphocytes in altered gravity during parabolic flight and clinostat experiments.

    Science.gov (United States)

    Tauber, Svantje; Hauschild, Swantje; Paulsen, Katrin; Gutewort, Annett; Raig, Christiane; Hürlimann, Eva; Biskup, Josefine; Philpot, Claudia; Lier, Hartwin; Engelmann, Frank; Pantaleo, Antonella; Cogoli, Augusto; Pippia, Proto; Layer, Liliana E; Thiel, Cora S; Ullrich, Oliver

    2015-01-01

    Several limiting factors for human health and performance in microgravity have been clearly identified arising from the immune system, and substantial research activities are required in order to provide the basic information for appropriate integrated risk management. The gravity-sensitive nature of cells of the immune system renders them an ideal biological model in search for general gravity-sensitive mechanisms and to understand how the architecture and function of human cells is related to the gravitational force and therefore adapted to life on Earth. We investigated the influence of altered gravity in parabolic flight and 2D clinostat experiments on key proteins of activation and signaling in primary T lymphocytes. We quantified components of the signaling cascade 1.) in non-activated T lymphocytes to assess the "basal status" of the cascade and 2.) in the process of activation to assess the signal transduction. We found a rapid decrease of CD3 and IL-2R surface expression and reduced p-LAT after 20 seconds of altered gravity in non-activated primary T lymphocytes during parabolic flight. Furthermore, we observed decreased CD3 surface expression, reduced ZAP-70 abundance and increased histone H3-acetylation in activated T lymphocytes after 5 minutes of clinorotation and a transient downregulation of CD3 and stable downregulation of IL-2R during 60 minutes of clinorotation. CD3 and IL-2R are downregulated in primary T lymphocytes in altered gravity. We assume that a gravity condition around 1g is required for the expression of key surface receptors and appropriate regulation of signal molecules in T lymphocytes. © 2015 S. Karger AG, Basel.

  18. Age-related differences in postural control in humans in response to a sudden deceleration generated by postural disturbance.

    Science.gov (United States)

    Okada, S; Hirakawa, K; Takada, Y; Kinoshita, H

    2001-07-01

    Age-related differences in postural control in response to a relatively large deceleration resulting from postural disturbance were investigated in eight normal elderly men (age range 67-72 years) and eight young men as controls (age range 19-22 years) using a moving platform. Data were obtained for the hip, knee and ankle angles, position of the centre of foot pressure (CFP), head acceleration, and muscle activity of the leg muscles. The elderly subjects had slower and larger ankle and hip joint movements, and CFP displacement in response to the disturbance compared to the young controls. The elderly subjects also had a delayed occurrence, and greater magnitude of peak acceleration of head rotation than did the young subjects. For the elderly subjects, the CFP was closely related to angular changes in the hip joint movement, but not to those of the ankle and knee joint movements. For the young subjects, on the other hand, the CFP was significantly correlated with angular change in the ankle joint. Cocontraction of the tibialis anterior and gastrocnemius muscles was observed in the elderly subjects. The results indicated that a movement pattern for postural correction in the elderly adults was different from that of the young adults. The elderly relied more on hip movements while the young controls relied on ankle movements to control postural stability.

  19. Climate change and human disturbance can lead to local extinction of Alpine rock ptarmigan: new insight from the western Italian Alps.

    Science.gov (United States)

    Imperio, Simona; Bionda, Radames; Viterbi, Ramona; Provenzale, Antonello

    2013-01-01

    Alpine grouses are particularly vulnerable to climate change due to their adaptation to extreme conditions and to their relict distributions in the Alps where global warming has been particularly marked in the last half century. Grouses are also currently threatened by habitat modification and human disturbance, and an assessment of the impact of multiple stressors is needed to predict the fate of Alpine populations of these birds in the next decades. We estimated the effect of climate change and human disturbance on a rock ptarmigan population living in the western Italian Alps by combining an empirical population modelling approach and stochastic simulations of the population dynamics under the a1B climate scenario and two different disturbance scenarios, represented by the development of a ski resort, through 2050.The early appearance of snow-free ground in the previous spring had a favorable effect on the rock ptarmigan population, probably through a higher reproductive success. On the contrary, delayed snowfall in autumn had a negative effect possibly due to a mismatch in time to molt to white winter plumage which increases predation risk. The regional climate model PROTHEUS does not foresee any significant change in snowmelt date in the study area, while the start date of continuous snow cover is expected to be significantly delayed. The net effect in the stochastic projections is a more or less pronounced (depending on the model used) decline in the studied population. The addition of extra-mortality due to collision with ski-lift wires led the population to fatal consequences in most projections. Should these results be confirmed by larger studies the conservation of Alpine populations would deserve more attention. To counterbalance the effects of climate change, the reduction of all causes of death should be pursued, through a strict preservation of the habitats in the present area of occurrence.

  20. Climate change and human disturbance can lead to local extinction of Alpine rock ptarmigan: new insight from the western Italian Alps.

    Directory of Open Access Journals (Sweden)

    Simona Imperio

    Full Text Available Alpine grouses are particularly vulnerable to climate change due to their adaptation to extreme conditions and to their relict distributions in the Alps where global warming has been particularly marked in the last half century. Grouses are also currently threatened by habitat modification and human disturbance, and an assessment of the impact of multiple stressors is needed to predict the fate of Alpine populations of these birds in the next decades. We estimated the effect of climate change and human disturbance on a rock ptarmigan population living in the western Italian Alps by combining an empirical population modelling approach and stochastic simulations of the population dynamics under the a1B climate scenario and two different disturbance scenarios, represented by the development of a ski resort, through 2050.The early appearance of snow-free ground in the previous spring had a favorable effect on the rock ptarmigan population, probably through a higher reproductive success. On the contrary, delayed snowfall in autumn had a negative effect possibly due to a mismatch in time to molt to white winter plumage which increases predation risk. The regional climate model PROTHEUS does not foresee any significant change in snowmelt date in the study area, while the start date of continuous snow cover is expected to be significantly delayed. The net effect in the stochastic projections is a more or less pronounced (depending on the model used decline in the studied population. The addition of extra-mortality due to collision with ski-lift wires led the population to fatal consequences in most projections. Should these results be confirmed by larger studies the conservation of Alpine populations would deserve more attention. To counterbalance the effects of climate change, the reduction of all causes of death should be pursued, through a strict preservation of the habitats in the present area of occurrence.

  1. Cardiovascular Deconditioning in Humans: Alteration in Cardiovascular Regulation and Function During Simulated Microgravity

    Science.gov (United States)

    Cohen, Richard

    1999-01-01

    Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In this project we apply a powerful, new method - cardiovascular system identification (CSI) - for the study of the effects of space flight on the cardiovascular system so that effective countermeasures can be developed. CSI involves the mathematical analysis of second-to-second fluctuations in non-invasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV - respiratory activity) in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of all the physiologic mechanisms coupling these signals, CSI provides a model of the closed-loop cardiovascular regulatory state in an individual subject. The model includes quantitative descriptions of the heart rate baroreflex, autonomic function, as well as other important physiologic mechanisms. We are in the process of incorporating beat-to-beat fluctuations of stroke volume into the CSI technique in order to quantify additional physiologic mechanisms such as those involved in control of peripheral vascular resistance and alterations in cardiac contractility. We apply CSI in conjunction with the two general protocols of the Human Studies Core project. The first protocol involves ground-based, human head down tilt bed rest to simulate microgravity and acute stressors - upright tilt, standing and bicycle exercise - to provide orthostatic and exercise challenges. The second protocol is intended to be the same as the first but with the addition of sleep deprivation to determine whether

  2. Human health alters the sustainability of fishing practices in East Africa.

    Science.gov (United States)

    Fiorella, Kathryn J; Milner, Erin M; Salmen, Charles R; Hickey, Matthew D; Omollo, Dan O; Odhiambo, Abdi; Mattah, Brian; Bukusi, Elizabeth A; Fernald, Lia C H; Brashares, Justin S

    2017-04-18

    Understanding feedbacks between human and environmental health is critical for the millions who cope with recurrent illness and rely directly on natural resources for sustenance. Although studies have examined how environmental degradation exacerbates infectious disease, the effects of human health on our use of the environment remains unexplored. Human illness is often tacitly assumed to reduce human impacts on the environment. By this logic, ill people reduce the time and effort that they put into extractive livelihoods and, thereby, their impact on natural resources. We followed 303 households living on Lake Victoria, Kenya over four time points to examine how illness influenced fishing. Using fixed effect conditional logit models to control for individual-level and time-invariant factors, we analyzed the effect of illness on fishing effort and methods. Illness among individuals who listed fishing as their primary occupation affected their participation in fishing. However, among active fishers, we found limited evidence that illness reduced fishing effort. Instead, ill fishers shifted their fishing methods. When ill, fishers were more likely to use methods that were illegal, destructive, and concentrated in inshore areas but required less travel and energy. Ill fishers were also less likely to fish using legal methods that are physically demanding, require travel to deep waters, and are considered more sustainable. By altering the physical capacity and outlook of fishers, human illness shifted their effort, their engagement with natural resources, and the sustainability of their actions. These findings show a previously unexplored pathway through which poor human health may negatively impact the environment.

  3. Epithelial membrane protein 2 (EMP2) deficiency alters placental angiogenesis, mimicking features of human placental insufficiency.

    Science.gov (United States)

    Williams, Carmen J; Chu, Alison; Jefferson, Wendy N; Casero, David; Sudhakar, Deepthi; Khurana, Nevil; Hogue, Claire P; Aryasomayajula, Chinmayi; Patel, Priya; Sullivan, Peggy; Padilla-Banks, Elizabeth; Mohandessi, Shabnam; Janzen, Carla; Wadehra, Madhuri

    2017-03-14

    Epithelial membrane protein-2 (EMP2) is a tetraspan protein predicted to regulate placental development. Highly expressed in secretory endometrium and trophectoderm cells, previous studies suggest that it may regulate implantation by orchestrating the surface expression of integrins and other membrane proteins. In order to test the role of EMP2 in pregnancy, mice lacking EMP2 (Emp2(-/-) ) were generated. Emp2(-/-) females are fertile but have reduced litter sizes when carrying Emp2(-/-) but not Emp2(+/-) fetuses. Placentas of Emp2(-/-) fetuses exhibit dysregulation in pathways related to neoangiogenesis, coagulation, and oxidative stress, and have increased fibrin deposition and altered vasculature. Given that these findings often occur due to placental insufficiency resulting in an oxygen-poor environment, the expression of hypoxia-inducible factor-1 alpha (HIF-1α) was examined. Placentas from Emp2(-/-) fetuses had increased total HIF-1α expression in large part through an increase in uterine NK (uNK) cells, demonstrating a unique interplay between uNK cells and trophoblasts modulated through EMP2. To determine if these results translated to human pregnancy, placentas from normal, term deliveries or those complicated by placental insufficiency resulting in intrauterine growth restriction (IUGR) were stained for EMP2. EMP2 was significantly reduced in both villous and extravillous trophoblast populations in IUGR placentas. Experiments in vitro using human trophoblast cells lines indicate that EMP2 modulates angiogenesis by altering HIF-1α expression. Our results reveal a novel role for EMP2 in regulating trophoblast function and vascular development in mice and humans and suggest it may be a new biomarker for placental insufficiency.

  4. Geochronology of recent lake sediments from Longgan Lake,middle reach of the Yangtze River,influenced by disturbance of human activities

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The impacts of human activities in Longgan Lake region on the distribution of 210Pb in lake sediment made it difficult to establish geochronological sequence. However, environmental proxies recorded these human activities and could be used as time marker to check 210Pb dating results. Based on the analysis of 210Pbexc distribution in cores LS-1 and LGL-1, and in combination with the human activities records in grain-size and element concentration, the sedimentation rates in the upper layers of these two cores were determined to be 0.19 and 0.23 cm/a respectively. The MAR (mass accumulation rates) of these two cores demonstrated that natural condition, such as precipitation and runoffs, led to the variation of MAR before human disturbance, and human activities controlled the sedimentary processes afterwards, which obviously reduced the particles influx into the lakes. During 1940s when human activity had not changed the water system within the catchment, 210Pb activity was abnormally strong in lakes along middle to lower reaches of the Yangtze River, which might be attributed to less precipitation and can be used as a time marker for geochronological research.

  5. Hyperspectral hybrid method classification for detecting altered mucosa of the human larynx

    Directory of Open Access Journals (Sweden)

    Martin Ron

    2012-06-01

    Full Text Available Abstract Background In the field of earth observation, hyperspectral detector systems allow precise target detections of surface components from remote sensing platforms. This enables specific land covers to be identified without the need to physically travel to the areas examined. In the medical field, efforts are underway to develop optical technologies that detect altering tissue surfaces without the necessity to perform an excisional biopsy. With the establishment of expedient classification procedures, hyperspectral imaging may provide a non-invasive diagnostic method that allows determination of pathological tissue with high reliability. In this study, we examined the performance of a hyperspectral hybrid method classification for the automatic detection of altered mucosa of the human larynx. Materials and methods Hyperspectral Imaging was performed in vivo and 30 bands from 390 to 680 nm for 5 cases of laryngeal disorders (2x hemorrhagic polyp, 3x leukoplakia were obtained. Image stacks were processed with unsupervised clustering (linear spectral unmixing, spectral signatures were extracted from unlabeled cluster maps and subsequently applied as end-members for supervised classification (spectral angle mapper of further medical cases with identical diagnosis. Results Linear spectral unmixing clearly highlighted altered mucosa as single spectral clusters in all cases. Matching classes were identified, and extracted spectral signatures could readily be applied for supervised classifications. Automatic target detection performed well, as the considered classes showed notable correspondence with pathological tissue locations. Conclusions Using hyperspectral classification procedures derived from remote sensing applications for diagnostic purposes can create concrete benefits for the medical field. The approach shows that it would be rewarding to collect spectral signatures from histologically different lesions of laryngeal disorders in

  6. Maraviroc reduces cytokine expression and secretion in human adipose cells without altering adipogenic differentiation.

    Science.gov (United States)

    Díaz-Delfín, Julieta; Domingo, Pere; Giralt, Marta; Villarroya, Francesc

    2013-03-01

    Maraviroc (MVC) is a drug approved for use as part of HAART in treatment-experienced HIV-1 patients with CCR5-tropic virus. Despite the current concerns on the alterations in adipose tissue that frequently appear in HIV-infected patients under HAART, there is no information available on the effects of MVC on adipose tissue. Here we studied the effects of MVC during and after the differentiation of human adipocytes in culture, and compared the results with the effects of efavirenz (EFV). We measured the acquisition of adipocyte morphology; the gene expression levels of markers for mitochondrial toxicity, adipogenesis and inflammation; and the release of adipokines and cytokines to the medium. Additionally, we determined the effects of MVC on lipopolysaccharide (LPS)-induced pro-inflammatory cytokine expression in adipocytes. Unlike EFV-treated pre-adipocytes, MVC-treated pre-adipocytes showed no alterations in the capacity to differentiate into adipocytes and accumulated lipids normally. Consistent with this, there were no changes in the mRNA levels of PPARγ or SREBP-1c, two master regulators of adipogenesis. In addition, MVC caused a significant decrease in the gene expression and release of pro-inflammatory cytokines, whereas EFV had the opposite effect. Moreover, MVC lowered inflammation-related gene expression and inhibited the LPS-induced expression of pro-inflammatory genes in differentiated adipocytes. We conclude that MVC does not alter adipocyte differentiation but rather shows anti-inflammatory properties by inhibiting the expression and secretion of pro-inflammatory cytokines. Collectively, our results suggest that MVC may minimize adverse effects on adipose tissue development, metabolism, and inflammation, and thus could be a potentially beneficial component of antiretroviral therapy.

  7. Bantu expansion shows that habitat alters the route and pace of human dispersals.

    Science.gov (United States)

    Grollemund, Rebecca; Branford, Simon; Bostoen, Koen; Meade, Andrew; Venditti, Chris; Pagel, Mark

    2015-10-27

    Unlike most other biological species, humans can use cultural innovations to occupy a range of environments, raising the intriguing question of whether human migrations move relatively independently of habitat or show preferences for familiar ones. The Bantu expansion that swept out of West Central Africa beginning ∼5,000 y ago is one of the most influential cultural events of its kind, eventually spreading over a vast geographical area a new way of life in which farming played an increasingly important role. We use a new dated phylogeny of ∼400 Bantu languages to show that migrating Bantu-speaking populations did not expand from their ancestral homeland in a "random walk" but, rather, followed emerging savannah corridors, with rainforest habitats repeatedly imposing temporal barriers to movement. When populations did move from savannah into rainforest, rates of migration were slowed, delaying the occupation of the rainforest by on average 300 y, compared with similar migratory movements exclusively within savannah or within rainforest by established rainforest populations. Despite unmatched abilities to produce innovations culturally, unfamiliar habitats significantly alter the route and pace of human dispersals.

  8. Molecular alterations in tumorigenic human bronchial and breast epithelial cells induced by high let radiation

    Science.gov (United States)

    Hei, T. K.; Zhao, Y. L.; Roy, D.; Piao, C. Q.; Calaf, G.; Hall, E. J.

    Carcinogenesis is a multi-stage process with sequence of genetic events governing the phenotypic expression of a series of transformation steps leading to the development of metastatic cancer. In the present study, immortalized human bronchial (BEP2D) and breast (MCF-10F) cells were irradiated with graded doses of either 150 keV/μm alpha particles or 1 GeV/nucleon 56Fe ions. Transformed cells developed through a series of successive steps before becoming tumorigenic in nude mice. Cell fusion studies indicated that radiation-induced tumorigenic phenotype in BEP2D cells could be completely suppressed by fusion with non-tumorigenic BEP2D cells. The differential expressions of known genes between tumorigenic bronchial and breast cells induced by alpha particles and their respective control cultures were compared using cDNA expression array. Among the 11 genes identified to be differentially expressed in BEP2D cells, three ( DCC, DNA-PK and p21 CIPI) were shown to be consistently down-regulated by 2 to 4 fold in all the 5 tumor cell lines examined. In contrast, their expressions in the fusion cell lines were comparable to control BEP2D cells. Similarly, expression levels of a series of genes were found to be altered in a step-wise manner among tumorigenic MCF-10F cells. The results are highly suggestive that functional alterations of these genes may be causally related to the carcinogenic process.

  9. Common raven occurrence in relation to energy transmission line corridors transiting human-altered sagebrush steppe

    Science.gov (United States)

    Coates, Peter S.; Howe, Kristy B.; Casazza, Michael L.; Delehanty, David J.

    2014-01-01

    Energy-related infrastructure and other human enterprises within sagebrush steppe of the American West often results in changes that promote common raven (Corvus corax; hereafter, raven) populations. Ravens, a generalist predator capable of behavioral innovation, present a threat to many species of conservation concern. We evaluate the effects of detailed features of an altered landscape on the probability of raven occurrence using extensive raven survey (n= 1045) and mapping data from southern Idaho, USA. We found nonlinear relationships between raven occurrence and distances to transmission lines, roads, and facilities. Most importantly, raven occurrence was greater with presence of transmission lines up to 2.2 km from the corridor.We further explain variation in raven occurrence along anthropogenic features based on the amount of non-native vegetation and cover type edge, such that ravens select fragmented sagebrush stands with patchy, exotic vegetative introgression. Raven occurrence also increased with greater length of edge formed by the contact of big sagebrush (Artemisia tridentate spp.) with non-native vegetation cover types. In consideration of increasing alteration of sagebrush steppe, these findings will be useful for planning energy transmission corridor placement and other management activities where conservation of sagebrush obligate species is a priority.

  10. Positional and expressive alteration of prohibitin during the induced differentiation of human hepatocarcinoma SMMC-7721 cells

    Institute of Scientific and Technical Information of China (English)

    Dong-Hui Xu; Jian Tang; Qi-Fu Li; Song-Lin Shi; Xiang-Feng Chen; Ying Liang

    2008-01-01

    AIM: To explore the existence and distribution of prohibitin (PHB) in nuclear matrix and its co-localization with products of some related genes during the differentiation of human hepatocarcinoma SMMC-7721cells.METHODS: The nuclear matrix of the SHHC-7721 cells cultured with or without 5 x 10-3 mmol/L hexamethylene bisacetamide (HMBA) was selectively extracted.Western blot was used to analyze the expression of PHB in nuclear matrix; imrnunofluorescence microscope observation was used to analyze the distribution of PHB in cell. LCSM was used to observe the co-localization of PHB with products of oncogenes and tumor suppressor genes.RESULTS: Western blot analysis showed that PHB existed in the composition of nuclear matrix proteins and was down-regulated by HMBA treatment.Immunofluorescence observation revealed that PHB existed in the nuclear matrix, and its distribution regions and expression levels were altered after HMBA treatment. Laser scanning confocal microscopy revealed the co-localization between PHB and the products of oncogenes or tumor repression genes including c-fos, c-myc, p53 and Rb and its alteration of distributive area in the cells treated by HMBA.CONCLUSION: These data confirm that PHB is a nuclear matrix protein, which is located in the nuclear matrix, and the distribution and expression of PHB and its relation with associated genes may play significant roles during the differentiation of SMHC-7721 cells.

  11. Grooved surface topography alters matrix-metalloproteinase production by human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Brydone, Alistair S; Dominic Meek, R M [Department of Orthopaedics, Southern General Hospital, 1345 Govan Road, Glasgow G51 4TF (United Kingdom); Dalby, Matthew J; Berry, Catherine C; McNamara, Laura E, E-mail: alibrydone@gmail.com [Centre for Cell Engineering, Joseph Black Building, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ (United Kingdom)

    2011-06-15

    Extracellular matrix (ECM) remodelling is an essential physiological process in which matrix-metalloproteinases (MMPs) have a key role. Manipulating the manner in which cells produce MMPs and ECMs may enable the creation of a desired tissue type, i.e. effect repair, or the prevention of tissue invasion (e.g. metastasis). The aim of this project was to determine if culturing fibroblasts on grooved topography altered collagen deposition or MMP production. Human fibroblasts were seeded on planar or grooved polycaprolactone substrates (grooves were 12.5 {mu}m wide with varying depths of 240 nm, 540 nm or 2300 nm). Cell behaviour and collagen production were studied using fluorescence microscopy and the spent culture medium was assessed using gel zymography to detect MMPs. Total collagen deposition was high on the 240 nm deep grooves, but decreased as the groove depth increased, i.e. as cell contact guidance decreased. There was an increase in gelatinase on the 2300 nm deep grooved topography and there was a difference in the temporal expression of MMP-3 observed on the planar surface compared to the 540 nm and 2300 nm topographies. These results show that topography can alter collagen and MMP production. A fuller understanding of these processes may permit the design of surfaces tailored to tissue regeneration e.g. tendon repair.

  12. Low oxygen alters mitochondrial function and response to oxidative stress in human neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Yury M. Lages

    2015-12-01

    Full Text Available Oxygen concentration should be carefully regulated in all living tissues, beginning at the early embryonic stages. Unbalances in oxygen regulation can lead to cell death and disease. However, to date, few studies have investigated the consequences of variations in oxygen levels for fetal-like cells. Therefore, in the present work, human neural progenitor cells (NPCs derived from pluripotent stem cells grown in 3% oxygen (v/v were compared with NPCs cultured in 21% (v/v oxygen. Low oxygen concentrations altered the mitochondrial content and oxidative functions of the cells, which led to improved ATP production, while reducing generation of reactive oxygen species (ROS. NPCs cultured in both conditions showed no differences in proliferation and glucose metabolism. Furthermore, antioxidant enzymatic activity was not altered in NPCs cultured in 3% oxygen under normal conditions, however, when exposed to external agents known to induce oxidative stress, greater susceptibility to DNA damage was observed. Our findings indicate that the management of oxygen levels should be considered for in vitro models of neuronal development and drug screening.

  13. Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Christopher J. Sontag

    2014-05-01

    Full Text Available The microenvironment is a critical mediator of stem cell survival, proliferation, migration, and differentiation. The majority of preclinical studies involving transplantation of neural stem cells (NSCs into the CNS have focused on injured or degenerating microenvironments, leaving a dearth of information as to how NSCs differentially respond to intact versus damaged CNS. Furthermore, single, terminal histological endpoints predominate, providing limited insight into the spatiotemporal dynamics of NSC engraftment and migration. We investigated the early and long-term engraftment dynamics of human CNS stem cells propagated as neurospheres (hCNS-SCns following transplantation into uninjured versus subacutely injured spinal cords of immunodeficient NOD-scid mice. We stereologically quantified engraftment, survival, proliferation, migration, and differentiation at 1, 7, 14, 28, and 98 days posttransplantation, and identified injury-dependent alterations. Notably, the injured microenvironment decreased hCNS-SCns survival, delayed and altered the location of proliferation, influenced both total and fate-specific migration, and promoted oligodendrocyte maturation.

  14. Post-disturbance dust emissions in dry lands: the role of anthropogenic and climatic factors

    Science.gov (United States)

    Ravi, S.; Zobeck, T. M.; Sankey, J. B.

    2012-12-01

    Disturbances, which cause a temporary reduction in vegetation cover, can greatly accelerate soil erosion by wind and subsequent dust emissions from desert grasslands and shrublands. These ecosystems worldwide are threatened by contemporary shifts in vegetation composition (e.g. encroachment by shrubs, invasion by exotic grasses) and climatic changes (e.g. increase in aridity, droughts), which alter the frequency and intensity of disturbances and dust emissions. Considering the deleterious impact of dust-borne contaminants on regional air quality and human health, accelerated post-disturbance aeolian transport is an increasingly serious concern for ecosystem management and risk assessment. Here, using extensive wind tunnel studies, field experiments (in grasslands and shrublands of North America) and modeling, we investigated the role of disturbances (fires, grazing) and changes in hydroclimatic factors (air humidity, soil moisture) in altering aeolian processes in desert grassland and shrublands. Our results indicate that the degree of post-disturbance aeolian transport and its attenuation with time was found to be strongly affected by the antecedent vegetation type and post-disturbance climatic conditions. The interactions among sediment transport processes, disturbances and hydroclimatic factors are explored from patch to landscape scales and their roles in dust emissions and land degradation are discussed.

  15. Alterations in cell surface area and deformability of individual human red blood cells in stored blood

    CERN Document Server

    Park, HyunJoo; Lee, SangYun; Kim, Kyoohyun; Sohn, Yong-Hak; Jang, Seongsoo; Park, YongKeun

    2015-01-01

    The functionality and viability of stored human red blood cells (RBCs) is an important clinical issue in transfusion. To systematically investigate changes in stored whole blood, the hematological properties of individual RBCs were quantified in blood samples stored for various periods with and without a preservation solution called CPDA-1. With 3-D quantitative phase imaging techniques, the optical measurements of the 3-D refractive index (RI) distributions and membrane fluctuations were done at the individual cell level. From the optical measurements, the morphological (volume, surface area and sphericity), biochemical (hemoglobin content and concentration), and mechanical parameters (dynamic membrane fluctuation) were simultaneously quantified to investigate the functionalities and their progressive alterations in stored RBCs. Our results show that the stored RBCs without CPDA-1 had a dramatic morphological transformation from discocytes to spherocytes within 2 weeks which was accompanied with significant ...

  16. Ischemia Alters the Expression of Connexins in the Aged Human Brain

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    Taizen Nakase

    2009-01-01

    Full Text Available Although the function of astrocytic gap junctions under ischemia is still under debate, increased expression of connexin 43 (Cx43 has been observed in ischemic brain lesions, suggesting that astrocytic gap junctions could provide neuronal protection against ischemic insult. Moreover, different connexin subtypes may play different roles in pathological conditions. We used immunohistochemical analysis to investigate alterations in the expression of connexin subtypes in human stroke brains. Seven samples, sectioned after brain embolic stroke, were used for the analysis. Data, evaluated semiquantitatively by computer-assisted densitometry, was compared between the intact hemisphere and ischemic lesions. The results showed that the coexpression of Cx32 and Cx45 with neuronal markers was significantly increased in ischemic lesions. Cx43 expression was significantly increased in the colocalization with astrocytes and relatively increased in the colocalization with neuronal marker in ischemic lesions. Therefore, Cx32, Cx43, and Cx45 may respond differently to ischemic insult in terms of neuroprotection.

  17. Varicella zoster virus infection of human fetal lung cells alters mitochondrial morphology.

    Science.gov (United States)

    Keller, Amy C; Badani, Hussain; McClatchey, P Mason; Baird, Nicholas L; Bowlin, Jacqueline L; Bouchard, Ron; Perng, Guey-Chuen; Reusch, Jane E B; Kaufer, Benedikt B; Gilden, Don; Shahzad, Aamir; Kennedy, Peter G E; Cohrs, Randall J

    2016-10-01

    Varicella zoster virus (VZV) is a ubiquitous alphaherpesvirus that establishes latency in ganglionic neurons throughout the neuraxis after primary infection. Here, we show that VZV infection induces a time-dependent significant change in mitochondrial morphology, an important indicator of cellular health, since mitochondria are involved in essential cellular functions. VZV immediate-early protein 63 (IE63) was detected in mitochondria-rich cellular fractions extracted from infected human fetal lung fibroblasts (HFL) by Western blotting. IE63 interacted with cytochrome c oxidase in bacterial 2-hybrid analyses. Confocal microscopy of VZV-infected HFL cells at multiple times after infection revealed the presence of IE63 in the nucleus, mitochondria, and cytoplasm. Our data provide the first evidence that VZV infection induces alterations in mitochondrial morphology, including fragmentation, which may be involved in cellular damage and/or death during virus infection.

  18. A method for assessing the physical recovery of Antarctic desert pavements following human-induced disturbances: a case study in the Ross Sea region of Antarctica.

    Science.gov (United States)

    O'Neill, Tanya A; Balks, Megan R; López-Martínez, Jerónimo; McWhirter, Judi L

    2012-12-15

    With increasing visitor numbers an understanding of the impacts of human activities in Antarctic terrestrial environments has become important. The objective of this study was to develop a means for assessing recovery of the ground surface desert pavement following physical disturbance. A set of 11 criteria were identified to assess desert pavement recovery. Assessed criteria were: embeddedness of surface clasts; impressions of removed clasts; degree of clast surface weathering; % overturned clasts; salt on underside of clasts; development of salt coatings; armouring per m(2); colour contrast; evidence of subsidence/melt out; accumulation of salt on cut surfaces; and evidence of patterned ground development. Recovery criteria were assigned a severity/extent rating on a scale from zero to four, zero being highly disturbed, and four being undisturbed. A relative % recovery for each criteria was calculated for each site by comparison with a nearby undisturbed control area, and an overall Mean Recovery Index (MRI) was assigned to each pavement surface. To test the method, 54 sites in the Ross Sea region of Antarctica were investigated including areas disturbed by: bulldozer scraping for road-fill, contouring for infrastructure, geotechnical investigations, and experimental treading trial sites. Disturbances had occurred at timescales ranging from one week to 50 years prior to assessment. The extent of desert pavement recovery at the sites investigated in this study was higher than anticipated. Fifty of the 54 sites investigated were in an intermediate, or higher, stage of desert pavement recovery, 30 sites were in an advanced stage of recovery, and four sites were indistinguishable from adjacent control sites (MRI = 100%). It was found that active surfaces, such as the gravel beach deposits at the Greenpeace World Park Base site at Cape Evans, the aeolian sand deposits at Bull Pass, and the alluvial fan deposits of the Loop Moraine field campsite, recovered relatively

  19. Low dose chronic treatment of human keratinocytes with inorganic arsenic causes hyperproliferation and altered protein phosphorylation

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    Steinberg, M.L. [City College of New York, NY (United States); Su, L.; Snow, E.T. [New York Univ. Medical Center, Tuxedo, NY (United States)]|[City College of New York, NY (United States)

    1997-10-01

    Chronic exposure to arsenate [As(V)] or arsenite [As(III)] causes hyperproliferation of normal and SV40-transformed human epidermal keratinocytes. Line 327 SV40-infected human keratinocytes were grown in the presence of either As(III) or As(V) (0.01 to 10 {mu}M) in complete medium for seven days prior to harvesting and counting. Both As(III) and As(V) were cytotoxic at micromolar concentrations, however submicromolar arsenic caused a significant increase in cell growth. Cell numbers in cultures exposed to As(V) were increased more than 186% relative to controls, and an even larger stimulation in cell growth was observed after treatment with 50 nM As(III). Normal non-SV40 T-antigen. Preliminary cell cycle analysis using unselected, log-phase cultures of arsenic-treated keratinocytes shows an increased proportion of cells in S- and G2/M-phase. Isoelectric focusing of phosphotyrosine-containing proteins from cells labeled with {sup 32}P-inorganic phosphate showed that the hyperproliferation of keratinocytes grown in low concentrations of arsenic is accompanied by altered tyrosine-specific protein phosphorylation. A number of phosphorylated proteins were observed in As-treated cells that were not observed in the controls; and minor bands at IEPs of 3.0, 4.2, 7.2, 7.5 and 8.2. These results, together with the lack of direct enzyme inhibition by arsenic shown by Su et al., this volume, suggest that arsenic-induced skin lesions and carcinogenesis may be the result of altered cell cycle control rather than DNA damage or reduced DNA repair.

  20. Endoplasmic reticulum stress induces different molecular structural alterations in human dilated and ischemic cardiomyopathy.

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    Ana Ortega

    Full Text Available BACKGROUND: The endoplasmic reticulum (ER is a multifunctional organelle responsible for the synthesis and folding of proteins as well as for signalling and calcium storage, that has been linked to the contraction-relaxation process. Perturbations of its homeostasis activate a stress response in diseases such as heart failure (HF. To elucidate the alterations in ER molecular components, we analyze the levels of ER stress and structure proteins in human dilated (DCM and ischemic (ICM cardiomyopathies, and its relationship with patient's functional status. METHODS AND RESULTS: We examined 52 explanted human hearts from DCM (n = 21 and ICM (n = 21 subjects and 10 non-failing hearts as controls. Our results showed specific changes in stress (IRE1, p<0.05; p-IRE1, p<0.05 and structural (Reticulon 1, p<0.01 protein levels. The stress proteins GRP78, XBP1 and ATF6 as well as the structural proteins RRBP1, kinectin, and Nogo A and B, were upregulated in both DCM and ICM patients. Immunofluorescence results were concordant with quantified Western blot levels. Moreover, we show a novel relationship between stress and structural proteins. RRBP1, involved in procollagen synthesis and remodeling, was related with left ventricular function. CONCLUSIONS: In the present study, we report the existence of alterations in ER stress response and shaping proteins. We show a plausible effect of the ER stress on ER structure in a suitable sample of DCM and ICM subjects. Patients with higher values of RRBP1 had worse left ventricular function.

  1. Clinical implications of disturbances of uterine vascular morphology and function.

    Science.gov (United States)

    Hickey, M; Fraser, I S

    2000-12-01

    Menstrual disturbances are one of the most common problems presenting to the gynaecologist. In order for the endometrium to bleed, vessels must break down. Disruption in the regulation of endometrial vascular growth and function has been found in association with spontaneous and sex steroid-induced disturbances of menstrual bleeding. Although circulating oestrogens and progestogens influence the endometrial vessels, this effect appears to be indirect, and regulation is primarily via local factors. Deficient vasoconstriction and haemostasis with excessive fibrinolysis is seen in menorrhagia. Breakthrough bleeding in users of progestogen-only contraceptives is associated with increased superficial vascular fragility and disruptions in the supporting basement membrane. Blood vessels in uterine fibroids are abnormal in distribution and appearance. Adenomyosis is also commonly associated with menstrual disturbance, and alterations in vascular distribution suggest altered angiogenesis. Successful human embryo implantation requires endometrial vascular breakdown. Excessive thrombosis associated with the antiphospholipid syndrome may interfere with this re-modelling and compromise implantation. Arteriovenous malformations are a rare but important cause of excessive or irregular vaginal bleeding. Abundant vessels with abnormal morphology, associated with aberrant angiogenesis can be seen, and embolization of these vessels may be an effective conservative treatment. Improved understanding of the regulation of the uterine vasculature is likely to lead to targeted therapies to prevent unscheduled vascular breakdown and to control menstrual disturbance at an endometrial level.

  2. Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

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    Marcinkiewicz, Katarzyna M.; Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu

    2014-01-01

    To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. - Highlights: • RNAseq elucidates differences between non-tumorigenic and tumorigenic oral keratinocytes. • Changes in HOX mRNA in SCC-9 vs. OKF6-TERT1R cells are a result of altered epigenetic regulation. • RNAseq shows that retinoic acid (RA) influences gene expression in both OKF6-TERT1R and SCC-9 cells.

  3. [Autotelic activities aimed at the alteration of the human body from socially accepted to pathological forms: about non-suicidal self-injury].

    Science.gov (United States)

    Kalmar, Sandor

    2016-03-01

    The author lays down that non-suicidal self-injury (NSSI) constitutes an increasingly more common and serious public health problem, especially during the age of adolescence. In spite of the fact that the phenomenon has been known since the beginning of human mankind even in animals, we have not been able to either give a clear explanation or prevent its spreading yet. The author reviews the conceptual disturbances, behavioural phenotypes, cultural-historical and mythological antecedents related to self-injury, just as the controversial concepts, reasons of unclearness of the concepts, and clinical classification of self-injuries, and he outlines a new categorisation/ classification of the explanation of autotelic activities aimed at the alteration of the human body. He reviews the relationship between self-injuries and other psychological signs and symptoms and psychiatric illnesses, the explanations of developing self-injurious behaviour and further research directions. Besides the different models of self-injury he presents a holistic model. Besides the therapeutic guidelines of self-injurious behaviour, he calls the attention to the importance of genetic and nervous system researches, psychological and spiritual research, the importance of mental education and prevention, and he also lists some more essential questions future researchers have to find the answers for if we would like all children to be allowed to enter the adults' world in a healthy and sound state.

  4. Complete artificial saliva alters expression of proinflammatory cytokines in human dermal fibroblasts.

    Science.gov (United States)

    Malpass, Gloria E; Arimilli, Subhashini; Prasad, Gaddamanugu L; Howlett, Allyn C

    2013-07-01

    Complete artificial saliva (CAS) is a saliva substitute often used as a vehicle for test articles, including smokeless tobacco products. In the course of a study employing normal adult human dermal fibroblasts (HDFa) as a model in vitro, we discovered that CAS as a vehicle introduced a significant change in the expression of proinflammatory cytokines. To determine the effects of CAS on gene expression, real-time quantitative reverse-transcriptase PCR gene array analysis was used. Results indicate that robust changes in the expression of the proinflammatory cytokine interleukin 8 (IL8) and the vascular cell adhesion molecule 1 (VCAM1) occur within 5h of exposure to CAS. To determine whether CAS also alters cytokine release into the culture media, cytometric bead array assays for human inflammatory cytokines were performed. Analysis shows that CAS induced the release of IL8 and IL6. This study focused on determining which components in CAS were responsible for the proinflammatory response in HDFa. The following components were investigated: α-amylase, lysozyme, acid phosphatase, and urea. Results demonstrated that enzymatically active α-amylase induced gene expression for proinflammatory cytokines IL8, IL6, tumor necrosis factor-α, and IL1α and for VCAM1. Therefore, it is important to carefully evaluate the "vehicle effects" of CAS and its components in in vitro toxicology research.

  5. Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain.

    Science.gov (United States)

    Miksys, Sharon; Lerman, Caryn; Shields, Peter G; Mash, Deborah C; Tyndale, Rachel F

    2003-07-01

    CYP2B6 metabolizes drugs such as nicotine and bupropion, and many toxins and carcinogens. Nicotine induces CYP2B1 in rat brain and in humans polymorphic variation in CYP2B6 affects smoking cessation rates. The aim of this study was to compare CYP2B6 expression in brains of human smokers and non-smokers and alcoholics and non-alcoholics (n=26). CYP2B6 expression was brain region-specific, and was observed in both neurons and astrocytes. CYP2B6 levels were higher in brains of smokers and alcoholics, particularly in cerebellar Purkinje cells and hippocampal pyramidal neurons, cells known to be damaged in alcoholics. Significantly more (penzyme levels, stability and activity. Preliminary genotyping of this small sample (n=24) suggested that individuals with the CC genotype had higher brain CYP2B6 than those with the CT or TT genotype. Higher brain CYP2B6 activity in smokers and alcoholics may cause altered sensitivity to centrally acting drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and contribute to central tolerance to nicotine.

  6. Alteration or adaptation, the two roads for human gastric mucin glycosylation infected by Helicobacter pylori.

    Science.gov (United States)

    Joncquel Chevalier Curt, Marie; Lecointe, Karine; Mihalache, Adriana; Rossez, Yannick; Gosset, Pierre; Léonard, Renaud; Robbe-Masselot, Catherine

    2015-06-01

    Helicobacter pylori is a Gram-negative bacterium that colonizes the mucus niche of the gastric mucosa and infects more than half of the world's human population. Chronic infection may cause gastritis, duodenal ulcer, intestinal metaplasia or gastric cancer. In the stomach, H. pylori interacts with O-glycans of gastric mucins but the mechanism by which the bacteria succeed in altering the mucosa remains mainly unknown. To better understand the physiopathology of the infection, inhibitory adhesion assays were performed with various O-glycans expressed by human gastric mucins, and topographic expression of gastric mucins MUC5AC and MUC6 was analyzed for healthy uninfected individuals, for infected asymptomatic individuals and for patients infected by H. pylori and having the incomplete type of intestinal metaplasia. The glycosylation of the gastric mucosa of asymptomatic individuals infected by H. pylori was determined and compared with the glycosylation pattern found for patients with the incomplete type of intestinal metaplasia. Results show that H. pylori manages to modulate host's glycosylation during the course of infection in order to create a favorable niche, whereas asymptomatic infected individuals seem to counteract further steps of infection development by adapting their mucus glycosylation. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Rarity of DNA sequence alterations in the promoter region of the human androgen receptor gene

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    D.F. Cabral

    2004-12-01

    Full Text Available The human androgen receptor (AR gene promoter lies in a GC-rich region containing two principal sites of transcription initiation and a putative Sp1 protein-binding site, without typical "TATA" and "CAAT" boxes. It has been suggested that mutations within the 5'untranslated region (5'UTR may contribute to the development of prostate cancer by changing the rates of gene transcription and/or translation. In order to investigate this question, the aim of the present study was to search for the presence of mutations or polymorphisms at the AR-5'UTR in 92 prostate cancer patients, where histological diagnosis of adenocarcinoma was established in specimens obtained from transurethral resection or after prostatectomy. The AR-5'UTR was amplified by PCR from genomic DNA samples of the patients and of 100 healthy male blood donors, included as controls. Conformation-sensitive gel electrophoresis was used for DNA sequence alteration screening. Only one band shift was detected in one individual from the blood donor group. Sequencing revealed a new single nucleotide deletion (T in the most conserved portion of the promoter region at position +36 downstream from the transcription initiation site I. Although the effect of this specific mutation remains unknown, its rarity reveals the high degree of sequence conservation of the human androgen promoter region. Moreover, the absence of detectable variation within the critical 5'UTR in prostate cancer patients indicates a low probability of its involvement in prostate cancer etiology.

  8. The secondary alcohol and aglycone metabolites of doxorubicin alter metabolism of human erythrocytes

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    F. Misiti

    2003-12-01

    Full Text Available Anthracyclines, a class of antitumor drugs widely used for the treatment of solid and hematological malignancies, cause a cumulative dose-dependent cardiac toxicity whose biochemical basis is unclear. Recent studies of the role of the metabolites of anthracyclines, i.e., the alcohol metabolite doxorubicinol and aglycone metabolites, have suggested new hypotheses about the mechanisms of anthracycline cardiotoxicity. In the present study, human red blood cells were used as a cell model. Exposure (1 h at 37ºC of intact human red blood cells to doxorubicinol (40 µM and to aglycone derivatives of doxorubicin (40 µM induced, compared with untreated red cells: i a ~2-fold stimulation of the pentose phosphate pathway (PPP and ii a marked inhibition of the red cell antioxidant enzymes, glutathione peroxidase (~20% and superoxide dismutase (~60%. In contrast to doxorubicin-derived metabolites, doxorubicin itself induced a slighter PPP stimulation (~35% and this metabolic event was not associated with any alteration in glutathione reductase, glutathione peroxidase, catalase or superoxide dismutase activity. Furthermore, the interaction of hemoglobin with doxorubicin and its metabolites induced a significant increase (~22% in oxygen affinity compared with hemoglobin incubated without drugs. On the basis of the results obtained in the present study, a new hypothesis, involving doxorubicinol and aglycone metabolites, has been proposed to clarify the mechanisms responsible for the doxorubicin-induced red blood cell toxicity.

  9. Microarray-bioinformatics analysis of altered genomic expression profiles between human fetal and infant myocardium

    Institute of Scientific and Technical Information of China (English)

    KONG Bo; LIU Ying-long; L(U) Xiao-dong

    2008-01-01

    Background The physiological differences between fetal and postnatal heart have been well characterized at the cellular level. However, the genetic mechanisms governing and regulating these differences have only been partially elucidated. Elucidation of the differentially expressed genes profile before and after birth has never been systematically proposed and analyzed.Methods The human oligonuclectide microarray and bioinformatics analysis approaches were applied to isolate and classify the differentially expressed genes between fetal and infant cardiac tissue samples. Quantitative real-time PCR was used to confirm the results from the microarray.Results Two hundred and forty-two differentially expressed genes were discovered and classified into 13 categories, including genes related to energy metabolism, myocyte hyperplasia, development, muscle contraction, protein synthesis and degradation, extraceUular matrix components, transcription factors, apoptosis, signal pathway molecules, organelle organization and several other biological processes. Moreover, 95 genes were identified which had not previously been reported to be expressed in the heart.Conclusions The study systematically analyzed the alteration of the gene expression profile between the human fetal and infant myocardium. A number of genes were discovered which had not been reported to be expressed in the heart. The data provided insight into the physical development mechanisms of the heart before and after birth.KONG Bo and LU Xiao-dong contributed equally to this study.

  10. Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.

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    Cleo Robinson

    Full Text Available Mesothelioma is principally caused by asbestos and may be preventable because there is a long latent period between exposure and disease development. The most at-risk are a relatively well-defined population who were exposed as a consequence of their occupations. Although preventative agents investigated so far have not been promising, discovery of such an agent would have a significant benefit world-wide on healthcare costs and personal suffering. Statins are widely used for management of hypercholesterolemia and cardiovascular risk; they can induce apoptosis in mesothelioma cells and epidemiological data has linked their use to a lower incidence of cancer. We hypothesised that statins would inhibit the development of asbestos-induced mesothelioma in mice and humans. An autochthonous murine model of asbestos-induced mesothelioma was used to test this by providing atorvastatin daily in the feed at 100 mg/kg, 200 mg/kg and 400 mg/kg. Continuous administration of atorvastatin did not alter the rate of disease development nor increase the length of time that mice survived. Latency to first symptoms of disease and disease progression were also unaffected. In a parallel study, the relationship between the use of statins and development of mesothelioma was investigated in asbestos-exposed humans. In a cohort of 1,738 asbestos exposed people living or working at a crocidolite mine site in Wittenoom, Western Australia, individuals who reported use of statins did not have a lower incidence of mesothelioma (HR = 1.01; 95% CI = 0.44-2.29, p = 0.99. Some individuals reported use of both statins and non-steroidal anti-inflammatory drugs or COX-2 inhibitors, and these people also did not have an altered risk of mesothelioma development (HR = 1.01; 95% CI = 0.61-1.67, p = 0.97. We conclude that statins do not moderate the rate of development of mesothelioma in either a mouse model or a human cohort exposed to asbestos.

  11. Developmental exposure to estrogen alters differentiation and epigenetic programming in a human fetal prostate xenograft model.

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    Camelia M Saffarini

    Full Text Available Prostate cancer is the most frequent non-cutaneous malignancy in men. There is strong evidence in rodents that neonatal estrogen exposure plays a role in the development of this disease. However, there is little information regarding the effects of estrogen in human fetal prostate tissue. This study explored early life estrogen exposure, with and without a secondary estrogen and testosterone treatment in a human fetal prostate xenograft model. Histopathological lesions, proliferation, and serum hormone levels were evaluated at 7, 30, 90, and 200-day time-points after xenografting. The expression of 40 key genes involved in prostatic glandular and stromal growth, cell-cycle progression, apoptosis, hormone receptors and tumor suppressors was evaluated using a custom PCR array. Epigenome-wide analysis of DNA methylation was performed on whole tissue, and laser capture-microdissection (LCM isolated epithelial and stromal compartments of 200-day prostate xenografts. Combined initial plus secondary estrogenic exposures had the most severe tissue changes as revealed by the presence of hyperplastic glands at day 200. Gene expression changes corresponded with the cellular events in the KEGG prostate cancer pathway, indicating that initial plus secondary exposure to estrogen altered the PI3K-Akt signaling pathway, ultimately resulting in apoptosis inhibition and an increase in cell cycle progression. DNA methylation revealed that differentially methylated CpG sites significantly predominate in the stromal compartment as a result of estrogen-treatment, thereby providing new targets for future investigation. By using human fetal prostate tissue and eliminating the need for species extrapolation, this study provides novel insights into the gene expression and epigenetic effects related to prostate carcinogenesis following early life estrogen exposure.

  12. Numerical Models of Human Circulatory System under Altered Gravity: Brain Circulation

    Science.gov (United States)

    Kim, Chang Sung; Kiris, Cetin; Kwak, Dochan; David, Tim

    2003-01-01

    A computational fluid dynamics (CFD) approach is presented to model the blood flow through the human circulatory system under altered gravity conditions. Models required for CFD simulation relevant to major hemodynamic issues are introduced such as non-Newtonian flow models governed by red blood cells, a model for arterial wall motion due to fluid-wall interactions, a vascular bed model for outflow boundary conditions, and a model for auto-regulation mechanism. The three-dimensional unsteady incompressible Navier-Stokes equations coupled with these models are solved iteratively using the pseudocompressibility method and dual time stepping. Moving wall boundary conditions from the first-order fluid-wall interaction model are used to study the influence of arterial wall distensibility on flow patterns and wall shear stresses during the heart pulse. A vascular bed modeling utilizing the analogy with electric circuits is coupled with an auto-regulation algorithm for multiple outflow boundaries. For the treatment of complex geometry, a chimera overset grid technique is adopted to obtain connectivity between arterial branches. For code validation, computed results are compared with experimental data for steady and unsteady non-Newtonian flows. Good agreement is obtained for both cases. In sin-type Gravity Benchmark Problems, gravity source terms are added to the Navier-Stokes equations to study the effect of gravitational variation on the human circulatory system. This computational approach is then applied to localized blood flows through a realistic carotid bifurcation and two Circle of Willis models, one using an idealized geometry and the other model using an anatomical data set. A three- dimensional anatomical Circle of Willis configuration is reconstructed from human-specific magnetic resonance images using an image segmentation method. The blood flow through these Circle of Willis models is simulated to provide means for studying gravitational effects on the brain

  13. Epidemology and clinical aspects of human rabies in Minas Gerais, Brasil: misdiagnosis and misunderstandings on the psychopathological disturbances

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    Jayme Neves

    1980-12-01

    Full Text Available This paper reports 40 cases of human rabies studied at the Carlos Chagas Hospital of UFMC, State of Minas Gerais, Brazil, from 1963 through 1976. From the epidemioiogical point of view it is concluded that the magnitude of the problem of human rabies in underdeveioped countries remains quite unknown. Speciai emphasis is given to the lack of apropriate knowledge of the recommended preventive measures, and to the influence of health education and socio-economic-cultural structure of the communities. The classic clinical picture of human rabies is briefiy described, particular attention being drawn to psychopathologic features of rabies encephalomyeiitis. it is pointed out that in some cases the mental symptoms may predominate from the onset of the illness, adding difficuity to the diagnosis. According to the Authors, human rabies must be differentiated from several psychopathologic syndromes and also from encephalomyelitis due to other central nervous system infections. It is discussed whether the fataiistic concept of human rabies would be somehow contributing to delay a better understanding of the natural history of the disease.

  14. Genomic DNA copy-number alterations of the let-7 family in human cancers.

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    Yanling Wang

    Full Text Available In human cancer, expression of the let-7 family is significantly reduced, and this is associated with shorter survival times in patients. However, the mechanisms leading to let-7 downregulation in cancer are still largely unclear. Since an alteration in copy-number is one of the causes of gene deregulation in cancer, we examined copy number alterations of the let-7 family in 2,969 cancer specimens from a high-resolution SNP array dataset. We found that there was a reduction in the copy number of let-7 genes in a cancer-type specific manner. Importantly, focal deletion of four let-7 family members was found in three cancer types: medulloblastoma (let-7a-2 and let-7e, breast cancer (let-7a-2, and ovarian cancer (let-7a-3/let-7b. For example, the genomic locus harboring let-7a-3/let-7b was deleted in 44% of the specimens from ovarian cancer patients. We also found a positive correlation between the copy number of let-7b and mature let-7b expression in ovarian cancer. Finally, we showed that restoration of let-7b expression dramatically reduced ovarian tumor growth in vitro and in vivo. Our results indicate that copy number deletion is an important mechanism leading to the downregulation of expression of specific let-7 family members in medulloblastoma, breast, and ovarian cancers. Restoration of let-7 expression in tumor cells could provide a novel therapeutic strategy for the treatment of cancer.

  15. Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells.

    Science.gov (United States)

    Lee, Andrew W; Hertel, Laura; Louie, Ryan K; Burster, Timo; Lacaille, Vashti; Pashine, Achal; Abate, Davide A; Mocarski, Edward S; Mellins, Elizabeth D

    2006-09-15

    Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are susceptible to productive infection by human CMV (HCMV). To investigate the impact of infection on this cell type, we examined HLA-DR biosynthesis and trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA-DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of HLA-DR was independent of expression of unique short US2-US11 region gene products by HCMV. Indeed, exposure to UV-inactivated virus, but not to conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature LC, implicating particle binding/penetration in this effect. Reduced surface levels reflected an altered distribution of HLA-DR because total cellular HLA-DR was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells, as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was implicated, as endocytosis of surface HLA-DR was not increased. Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR and revealed markedly fewer HLA-DR-positive dendritic projections in infected mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the dendrites themselves and immunofluorescence revealed that cytoskeletal elements crucial for the formation and maintenance of dendrites are disrupted in viral Ag-positive cells. Consistent with these dendrite effects, HCMV-infected mature LC exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus, HCMV impedes MHC class II molecule trafficking, dendritic projections, and migration of mature LC. These changes likely contribute to the reduced activation of CD4+ T cells by HCMV-infected mature LC.

  16. Comparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells

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    Eugenia Mata-Greenwood

    2017-05-01

    Full Text Available Background : Hypoxia inducible factor 1 alpha (HIF1A is a master regulator of acute hypoxia; however, with chronic hypoxia, HIF1A levels return to the normoxic levels. Importantly, the genes that are involved in the cell survival and viability under chronic hypoxia are not known. Therefore, we tested the hypothesis that chronic hypoxia leads to the upregulation of a core group of genes with associated changes in the promoter DNA methylation that mediates the cell survival under hypoxia.Results : We examined the effect of chronic hypoxia (3 days; 0.5% oxygen on human brain micro endothelial cells (HBMEC viability and apoptosis. Hypoxia caused a significant reduction in cell viability and an increase in apoptosis. Next, we examined chronic hypoxia associated changes in transcriptome and genome-wide promoter methylation. The data obtained was compared with 16 other microarray studies on chronic hypoxia. Nine genes were altered in response to chronic hypoxia in all 17 studies. Interestingly, HIF1A was not altered with chronic hypoxia in any of the studies. Furthermore, we compared our data to three other studies that identified HIF-responsive genes by various approaches. Only two genes were found to be HIF dependent. We silenced each of these 9 genes using CRISPR/Cas9 system. Downregulation of EGLN3 significantly increased the cell death under chronic hypoxia, whereas downregulation of ERO1L, ENO2, adrenomedullin, and spag4 reduced the cell death under hypoxia.Conclusions : We provide a core group of genes that regulates cellular acclimatization under chronic hypoxic stress, and most of them are HIF independent.

  17. N-glycan alterations are associated with drug resistance in human hepatocellular carcinoma

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    Nakagawa Takahito

    2007-05-01

    Full Text Available Abstract Background Correlations of disease phenotypes with glycosylation changes have been analysed intensively in the tumor biology field. Glycoforms potentially associated with carcinogenesis, tumor progression and cancer metastasis have been identified. In cancer therapy, drug resistance is a severe problem, reducing therapeutic effect of drugs and adding to patient suffering. Although multiple mechanisms likely underlie resistance of cancer cells to anticancer drugs, including overexpression of transporters, the relationship of glycans to drug resistance is not well understood. Results We established epirubicin (EPI – and mitoxantrone (MIT – resistant cell lines (HLE-EPI and HLE-MIT from the human hepatocellular carcinoma cell line (HLE. HLE-EPI and HLE-MIT overexpressed transporters MDR1/ABCB1 and BCRP/ABCG2, respectively. Here we compared the glycomics of HLE-EPI and HLE-MIT cells with the parental HLE line. Core fucosylated triantennary oligosaccharides were increased in the two resistant lines. We investigated mRNA levels of glycosyltransferases synthesizing this oligosaccharide, namely, N-acetylglucosaminyltransferase (GnT-IVa, GnT-IVb and α1,6-fucosyltransferase (α1,6-FucT, and found that α1,6-FucT was particularly overexpressed in HLE-MIT cells. In HLE-EPI cells, GnT-IVa expression was decreased, while GnT-IVb was increased. Both GnT-IVs were downregulated in HLE-MIT cells. HLE-MIT cells also showed decreases in fucosylated tetraantennary oligosaccharide, the product of GnT-V. GnT-V expression was decreased in both lines, but particularly so in HLE-MIT cells. Thus both N-glycan and glycosyltransferase expression was altered as cells acquired tolerance, suggesting novel mechanisms of drug resistance. Conclusion N-glycan and glycosyltransferase expression in HLE-EPI and HLE-MIT were analysed and presented that glycans altered according with acquired tolerance. These results suggested novel mechanisms of drug resistance.

  18. Human Immunodeficiency Virus-1 Alters Brain-derived Neurotrophic Factor Processing in neurons

    Science.gov (United States)

    Bachis, Alessia; Avdoshina, Valeriya; Zecca, Luigi; Parsadanian, Maia; Mocchetti, Italo

    2012-01-01

    The molecular mechanisms leading to synaptic simplification and neuronal apoptosis in human immunodeficiency virus type 1 (HIV) positive subjects are unknown. The HIV protein gp120 reduced the length of neuronal processes similarly to the proneurotrophin pro brain-derived neurotrophic factor (proBDNF). Intriguingly, the effects of both proBDNF and gp120 were blocked by inhibitors of the p75 neurotrophin receptor, suggesting that proBDNF and gp120 share a similar mechanism of neurotoxicity. Therefore, we tested the hypothesis that gp120 affects the release of proBDNF. Using rat primary neurons we observed that gp120 promotes a time-dependent intracellular and extracellular accumulation of proBDNF concomitantly with a decrease in mature BDNF. A similar imbalance in the ratio proBDNF/mature BDNF was confirmed in postmortem brains of HIV positive subjects cognitive and motor impaired. Therefore, it is conceivable to formulate the hypothesis that HIV neurotoxicity includes a gp120-mediated alteration of BDNF processing. To determine the cellular mechanism whereby gp120 produces an accumulation of proBDNF, we examined the levels of intracellular and extracellular enzymes that proteolytically cleave proBDNF, furin and tissue plasminogen, respectively. In rat neurons exposed to gp120, intracellular furin levels decreased prior to cell death whereas tissue plasminogen changed only during apoptosis. Our data suggest that HIV, through gp120, reduces proBDNF processing by affecting furin levels and therefore causes an altered balance between anti-apoptotic and pro-apoptotic neurotrophins. Our studies identify a new mechanism that may explain how HIV promotes neuronal injury. PMID:22787033

  19. Altered Protein Composition and Gene Expression in Strabismic Human Extraocular Muscles and Tendons

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    Agarwal, Andrea B.; Feng, Cheng-Yuan; Altick, Amy L.; Quilici, David R.; Wen, Dan; Johnson, L. Alan; von Bartheld, Christopher S.

    2016-01-01

    Purpose To determine whether structural protein composition and expression of key regulatory genes are altered in strabismic human extraocular muscles. Methods Samples from strabismic horizontal extraocular muscles were obtained during strabismus surgery and compared with normal muscles from organ donors. We used proteomics, standard and customized PCR arrays, and microarrays to identify changes in major structural proteins and changes in gene expression. We focused on muscle and connective tissue and its control by enzymes, growth factors, and cytokines. Results Strabismic muscles showed downregulation of myosins, tropomyosins, troponins, and titin. Expression of collagens and regulators of collagen synthesis and degradation, the collagenase matrix metalloproteinase (MMP)2 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)1 and TIMP2, was upregulated, along with tumor necrosis factor (TNF), TNF receptors, and connective tissue growth factor (CTGF), as well as proteoglycans. Growth factors controlling extracellular matrix (ECM) were also upregulated. Among 410 signaling genes examined by PCR arrays, molecules with downregulation in the strabismic phenotype included GDNF, NRG1, and PAX7; CTGF, CXCR4, NPY1R, TNF, NTRK1, and NTRK2 were upregulated. Signaling molecules known to control extraocular muscle plasticity were predominantly expressed in the tendon rather than the muscle component. The two horizontal muscles, medial and lateral rectus, displayed similar changes in protein and gene expression, and no obvious effect of age. Conclusions Quantification of proteins and gene expression showed significant differences in the composition of extraocular muscles of strabismic patients with respect to important motor proteins, elements of the ECM, and connective tissue. Therefore, our study supports the emerging view that the molecular composition of strabismic muscles is substantially altered. PMID:27768799

  20. Interaction matters: A perceived social partner alters the neural processing of human speech.

    Science.gov (United States)

    Rice, Katherine; Redcay, Elizabeth

    2016-04-01

    Mounting evidence suggests that social interaction changes how communicative behaviors (e.g., spoken language, gaze) are processed, but the precise neural bases by which social-interactive context may alter communication remain unknown. Various perspectives suggest that live interactions are more rewarding, more attention-grabbing, or require increased mentalizing-thinking about the thoughts of others. Dissociating between these possibilities is difficult because most extant neuroimaging paradigms examining social interaction have not directly compared live paradigms to conventional "offline" (or recorded) paradigms. We developed a novel fMRI paradigm to assess whether and how an interactive context changes the processing of speech matched in content and vocal characteristics. Participants listened to short vignettes--which contained no reference to people or mental states--believing that some vignettes were prerecorded and that others were presented over a real-time audio-feed by a live social partner. In actuality, all speech was prerecorded. Simply believing that speech was live increased activation in each participant's own mentalizing regions, defined using a functional localizer. Contrasting live to recorded speech did not reveal significant differences in attention or reward regions. Further, higher levels of autistic-like traits were associated with altered neural specialization for live interaction. These results suggest that humans engage in ongoing mentalizing about social partners, even when such mentalizing is not explicitly required, illustrating how social context shapes social cognition. Understanding communication in social context has important implications for typical and atypical social processing, especially for disorders like autism where social difficulties are more acute in live interaction. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Disturbances of ligand potency and enhanced degradation of the human glycine receptor at affected positions G160 and T162 originally identified in patients suffering from hyperekplexia

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    Sinem eAtak

    2015-12-01

    Full Text Available Ligand-binding of Cys-loop receptors is determined by N-terminal extracellular loop structures from the plus as well as from the minus side of two adjacent subunits in the pentameric receptor complex. An aromatic residue in loop B of the glycine receptor (GlyR undergoes direct interaction with the incoming ligand via cation-π interactions. Recently we showed that mutated residues in loop B identified from human patients suffering from hyperekplexia disturb ligand-binding. Here, we exchanged the affected human residues by amino acids found in related members of the Cys-loop receptor family to determine the effects of side chain volume for ion channel properties. GlyR variants were characterized in vitro following transfection into cell lines in order to analyze protein expression, trafficking, degradation and ion channel function. GlyR α1 G160 mutations significantly decrease glycine potency arguing for a positional effect on neighboring aromatic residues and consequently glycine-binding within the ligand-binding pocket. Disturbed glycinergic inhibition due to T162 α1 mutations is an additive effect of affected biogenesis and structural changes within the ligand-binding site. Protein trafficking from the ER towards ER-Golgi intermediate compartment, the secretory Golgi pathways and finally the cell surface is largely diminished, but still sufficient to deliver ion channels that are functional at least at high glycine concentrations. The majority of T162 mutant protein accumulates in the ER and is conducted to ER-associated proteasomal degradation. Hence, G160 is an important determinant during glycine binding. In contrast, T162 assigns primarily receptor biogenesis whereas exchanges in functionality are secondary effects thereof.

  2. Alterações nucleolares em algumas neuroviroses humanas Nucleolar alterations in some human viral infections of the nervous system

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    Alexandre Alberto de Alencar

    1973-01-01

    Full Text Available Neste trabalho estudamos alguns conceitos básicos sobre o nucléolo. Em seguida à apresentação do material de estudo, constante de casos de neuroviroses humanas, é feita um adescrição pormenorizada das alterações nucleares e nucleolares encontradas nas seguintes entidades mórbidas: polioencefalite subaguda com inclusões de DAWSON, leuco-encefalite subaguda esclerosante de VAN BOAGAERT, panencefalite nodular de PETTEDORING, poliomielite anterior aguda e raiva. As alterações nucleolares encontradas constam de hipertrofia inicial, a que se seguem profundas alterações em sua estrutura interna, sob a forma de vacuolizações e condensações granulares (os chamados nucleolinos de número e tamanhos variados. Alguns destes corpúsculos granulares, fortemente basófilos e que apresentam as mesmas características citoquímicas dos nucléolos, são lançados no carioplasma sob a forma de volumosos corpúsculos basófilos esferoidais. São feitos comentários sobre a natureza do fenômeno, concluindo-se que, tratando-se de uma ocorrência somente encontrada nas viroses, em certas formas de intoxicações e em determinados distúrbios genéticos, o seu aparecimento em um quadro histopatológico encefalítico ou mielítico permite, com segurança atribuir sua etiologia a um vírus. De todos os processos estudados, o que apresentou tais alterações nucleolares com maior exuberância foi a panencefalite nodular de PETTE-DORING.In this paper we studied the classic and modern concepts concerning the structure, composition, origen and function of the nucleole particularly in relation to the neuronal cells. The materal of study consisted of a number of cases of human neuroviroses. A detailed description of the nuclear and nucleolar alterations verfied in the following diseases was made: Dawson's Subacute Polioencephalitis, van Bogaert´s Sclerosing Subacute Leucoencephalitis, Pette Döring's Subacute Panencephalitis, Acute Anterior Poliomyelitis

  3. Altered Expression of Human Smooth Muscle Myosin Phosphatase Targeting (MYPT) Isovariants with Pregnancy and Labor.

    Science.gov (United States)

    Lartey, Jon; Taggart, Julie; Robson, Stephen; Taggart, Michael

    2016-01-01

    Myosin light-chain phosphatase is a trimeric protein that hydrolyses phosphorylated myosin II light chains (MYLII) to cause relaxation in smooth muscle cells including those of the uterus. A major component of the phosphatase is the myosin targeting subunit (MYPT), which directs a catalytic subunit to dephosphorylate MYLII. There are 5 main MYPT family members (MYPT1 (PPP1R12A), MYPT2 (PPP1R12B), MYPT3 (PPP1R16A), myosin binding subunit 85 MBS85 (PPP1R12C) and TIMAP (TGF-beta-inhibited membrane-associated protein (PPP1R16B)). Nitric oxide (NO)-mediated smooth muscle relaxation has in part been attributed to activation of the phosphatase by PKG binding to a leucine zipper (LZ) dimerization domain located at the carboxyl-terminus of PPP1R12A. In animal studies, alternative splicing of PPP1R12A can lead to the inclusion of a 31-nucleotide exonic segment that generates a LZ negative (LZ-) isovariant rendering the phosphatase less sensitive to NO vasodilators and alterations in PPP1R12ALZ- and LZ+ expression have been linked to phenotypic changes in smooth muscle function. Moreover, PPP1R12B and PPP1R12C, but not PPP1R16A or PPP1R16B, have the potential for LZ+/LZ- alternative splicing. Yet, by comparison to animal studies, the information on human MYPT genomic sequences/mRNA expressions is scant. As uterine smooth muscle undergoes substantial remodeling during pregnancy we were interested in establishing the patterns of expression of human MYPT isovariants during this process and also following labor onset as this could have important implications for determining successful pregnancy outcome. We used cross-species genome alignment, to infer putative human sequences not available in the public domain, and isovariant-specific quantitative PCR, to analyse the expression of mRNA encoding putative LZ+ and LZ- forms of PPP1R12A, PPP1R12B and PPP1R12C as well as canonical PPP1R16A and PPP1R16B genes in human uterine smooth muscle from non-pregnant, pregnant and in

  4. Inhibition of α-adrenergic tone disturbs the distribution of blood flow in the exercising human limb

    NARCIS (Netherlands)

    I. Heinonen (Ilkka); M. Wendelin-Saarenhovi (Maria); K. Kaskinoro (Kimmo); J. Knuuti (Juhani); M. Scheinin (Mika); K.K. Kalliokoski (Kari)

    2013-01-01

    textabstractThe role of neuronal regulation of human cardiovascular function remains incompletely elucidated, especially during exercise. Here we, by positron emission tomography, monitored tissue-specific blood flow (BF) changes in nine healthy young men during femoral arterial infusions of norepin

  5. DINOFLAGELLATE CYST RECORDS AND HUMAN DISTURBANCE IN TWO NEIGHBORING ESTUARIES, NEW BEDFORD HARBOR AND APPONAGANSETT BAY, MASSACHUSETTS, USA

    Science.gov (United States)

    The dinoflagellate cyst records in sediments from New Bedford Harbor and Apponagansett Bay demonstrate sensitivity to environmental change caused by human activity in the watersheds over the last 500 years. Changes in the species richness, as well as absolute and relative abundan...

  6. Proteome alteration induced by hTERT transfection of human fibroblast cells

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    Riou Jean-François

    2008-04-01

    Full Text Available Abstract Background Telomerase confers cellular immortality by elongating telomeres, thereby circumventing the Hayflick limit. Extended-life-span cells have been generated by transfection with the human telomerase reverse transcriptase (hTERT gene. hTERT transfected cell lines may be of outstanding interest to monitor the effect of drugs targeting the telomerase activity. The incidence of hTERT gene transfection at the proteome level is a prerequisite to that purpose. The effect of the transfection has been studied on the proteome of human fibroblast (WI38. Cytosolic and nuclear fractions of WI38 cells, empty vector transfected WI38 (WI38-HPV and hTERT WI38 cells were submitted to a 2D-DIGE (Two-Dimensional Differential In-Gel Electrophoresis analysis. Only spots that had a similar abundance in WI38 and WI38-HPV, but were differentially expressed in WI38 hTERT were selected for MS identification. This method directly points to the proteins linked with the hTERT expression. Number of false positive differentially expressed proteins has been excluded by using control WI38-HPV cells. The proteome alteration induced by hTERT WI38 transfection should be taken into account in subsequent use of the cell line for anti-telomerase drugs evaluation. Results 2D-DIGE experiment shows that 57 spots out of 2246 are significantly differentially expressed in the cytosolic fraction due to hTERT transfection, and 38 were confidently identified. In the nuclear fraction, 44 spots out of 2172 were selected in the differential proteome analysis, and 14 were identified. The results show that, in addition to elongating telomeres, hTERT gene transfection has other physiological roles, among which an enhanced ER capacity and a potent cell protection against apoptosis. Conclusion We show that the methodology reduces the complexity of the proteome analysis and highlights proteins implicated in other processes than telomere elongation. hTERT induced proteome changes suggest

  7. Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

    Science.gov (United States)

    Fernández, Esteban R; Olivera, Gabriela C; Quebrada Palacio, Luz P; González, Mariela N; Hernandez-Vasquez, Yolanda; Sirena, Natalia María; Morán, María L; Ledesma Patiño, Oscar S; Postan, Miriam

    2014-01-01

    Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

  8. Dietary Phenethyl Isothiocyanate Alters Gene Expression in Human Breast Cancer Cells

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    Young Jin Moon

    2011-01-01

    Full Text Available Phenethyl isothiocyanate (PEITC, a component in cruciferous vegetables, can block chemical carcinogenesis in animal models. Our objective was to determine the effect of treatment with PEITC on gene expression changes in MCF-7 human breast cancer cells in order to evaluate potential mechanisms involved in its chemopreventive effects. MCF-7 cells were treated for 48 hours with either PEITC (3 μM or the vehicle. Total RNA was extracted from cell membrane preparations, and labeled cDNA's representing the mRNA pool were reverse-transcribed directly from total RNA isolated for use in the microarray hybridizations. Two specific human GE Array Kits (Superarray Inc. that both contain 23 marker genes, related to signal transduction pathways or cancer/tumor suppression, plus 2 housekeeping genes (β-actin and GAPDH, were utilized. Arrays from treated and control cells (n=4 per group were evaluated using a Student's t-test. Gene expression was significantly induced for tumor protein p53 (p53, cyclin-dependent kinase inhibitor 1C (p57 Kip2, breast cancer Type 2 early onset (BRCA2, cAMP responsive element binding protein 2 (ATF-2, interleukin 2 (IL-2, heat shock 27 KD protein (hsp27, and CYP19 (aromatase. Induction of p57 Kip2, p53, BRCA2, IL-2, and ATF-2 would be expected to decrease cellular proliferation and increase tumor suppression and/or apoptosis. PEITC treatment produced significant alterations in some genes involved in tumor suppression and cellular proliferation/apoptosis that may be important in explaining the chemopreventive effects of PEITC.

  9. Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

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    Esteban R Fernández

    Full Text Available Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

  10. Adenosine receptor antagonists alter the stability of human epileptic GABAA receptors

    Science.gov (United States)

    Roseti, Cristina; Martinello, Katiuscia; Fucile, Sergio; Piccari, Vanessa; Mascia, Addolorata; Di Gennaro, Giancarlo; Quarato, Pier Paolo; Manfredi, Mario; Esposito, Vincenzo; Cantore, Gianpaolo; Arcella, Antonella; Simonato, Michele; Fredholm, Bertil B.; Limatola, Cristina; Miledi, Ricardo; Eusebi, Fabrizio

    2008-01-01

    We examined how the endogenous anticonvulsant adenosine might influence γ-aminobutyric acid type A (GABAA) receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 μM), GABAA receptors, microtransplanted into Xenopus oocytes from neurosurgically resected epileptic human nervous tissues, exhibited an obvious GABAA-current (IGABA) run-down, which was consistently and significantly reduced by treatment with the nonselective adenosine receptor antagonist CGS15943 (100 nM) or with adenosine deaminase (ADA) (1 units/ml), that inactivates adenosine. It was also found that selective antagonists of A2B (MRS1706, 10 nM) or A3 (MRS1334, 30 nM) receptors reduced IGABA run-down, whereas treatment with the specific A1 receptor antagonist DPCPX (10 nM) was ineffective. The selective A2A receptor antagonist SCH58261 (10 nM) reduced or potentiated IGABA run-down in ≈40% and ≈20% of tested oocytes, respectively. The ADA-resistant, AR agonist 2-chloroadenosine (2-CA) (10 μM) potentiated IGABA run-down but only in ≈20% of tested oocytes. CGS15943 administration again decreased IGABA run-down in patch-clamped neurons from either human or rat neocortex slices. IGABA run-down in pyramidal neurons was equivalent in A1 receptor-deficient and wt neurons but much larger in neurons from A2A receptor-deficient mice, indicating that, in mouse cortex, GABAA-receptor stability is tonically influenced by A2A but not by A1 receptors. IGABA run-down from wt mice was not affected by 2-CA, suggesting maximal ARs activity by endogenous adenosine. Our findings strongly suggest that cortical A2–A3 receptors alter the stability of GABAA receptors, which could offer therapeutic opportunities. PMID:18809912

  11. Tumor promoters alter the temporal program of adenovirus replication in human cells.

    Science.gov (United States)

    Fisher, P B; Young, C S; Weinstein, I B; Carter, T H

    1981-04-01

    In this study we evaluated the effect of phorbol ester tumor promoters on the kinetics of adenovirus type 5 (Ad5) replication in human cells. When added at the time of infection, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) accelerated the appearance of an early virus antigen (72,000-molecular-weight [72K] deoxyribonucleic acid-binding protein), the onset of viral deoxyribonucleic acid synthesis, and the production of infectious virus. The appearance of an Ad5-specific cytopathic effect (CPE) was also accelerated in infected cultures exposed to TPA, whereas phorbol, 4 alpha-phorbol-12,13-didecanoate and 4-OmeTPA, which are inactive as tumor promoters, were ineffective in inducing this morphological change. The acceleration of the CPE seen in TPA-treated Ad5-infected cells was not caused by TPA induction of the protease plasminogen activator, since the protease inhibitors leupeptin and antipain do not inhibit the earlier onset of this CPE and, in contrast, epidermal growth factor, which induces plasminogen activator in HeLa cells, does not induce an earlier CPE. Evidence for a direct effect of TPA on viral gene expression was obtained by analyzing viral messenger ribonucleic acid (mRNA) synthesis. TPA accelerated the appearance of mRNA from all major early regions of Ad5, transiently stimulated the accumulation of region III mRNA, and accelerated the appearance of late Ad5 mRNA. Thus, TPA altered the temporal program of Ad5 mRNA production and accelerated the appearance of at least some Ad5-specific polypeptides during lytic infection of human cells. These effects presumably explain the earlier onset of the Ad5-specific CPE in TPA-treated cells and may have relevance to the effects of TPA on viral gene expression in nonpermissive cells carrying integrated viral deoxyribonucleic acid sequences.

  12. Household air pollution causes dose-dependent inflammation and altered phagocytosis in human macrophages.

    Science.gov (United States)

    Rylance, Jamie; Fullerton, Duncan G; Scriven, James; Aljurayyan, Abdullah N; Mzinza, David; Barrett, Steve; Wright, Adam K A; Wootton, Daniel G; Glennie, Sarah J; Baple, Katy; Knott, Amy; Mortimer, Kevin; Russell, David G; Heyderman, Robert S; Gordon, Stephen B

    2015-05-01

    Three billion people are exposed to household air pollution from biomass fuel use. Exposure is associated with higher incidence of pneumonia, and possibly tuberculosis. Understanding mechanisms underlying these defects would improve preventive strategies. We used human alveolar macrophages obtained from healthy Malawian adults exposed naturally to household air pollution and compared them with human monocyte-derived macrophages exposed in vitro to respirable-sized particulates. Cellular inflammatory response was assessed by IL-6 and IL-8 production in response to particulate challenge; phagosomal function was tested by uptake and oxidation of fluorescence-labeled beads; ingestion and killing of Streptococcus pneumoniae and Mycobacterium tuberculosis were measured by microscopy and quantitative culture. Particulate ingestion was quantified by digital image analysis. We were able to reproduce the carbon loading of naturally exposed alveolar macrophages by in vitro exposure of monocyte-derived macrophages. Fine carbon black induced IL-8 release from monocyte-derived and alveolar macrophages (P < 0.05) with similar magnitude responses (log10 increases of 0.93 [SEM = 0.2] versus 0.74 [SEM = 0.19], respectively). Phagocytosis of pneumococci and mycobacteria was impaired with higher particulate loading. High particulate loading corresponded with a lower oxidative burst capacity (P = 0.0015). There was no overall effect on killing of M. tuberculosis. Alveolar macrophage function is altered by particulate loading. Our macrophage model is comparable morphologically to the in vivo uptake of particulates. Wood smoke-exposed cells demonstrate reduced phagocytosis, but unaffected mycobacterial killing, suggesting defects related to chronic wood smoke inhalation limited to specific innate immune functions.

  13. Epidemology and clinical aspects of human rabies in Minas Gerais, Brasil: misdiagnosis and misunderstandings on the psychopathological disturbances

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    Jayme Neves

    1980-12-01

    Full Text Available This paper reports 40 cases of human rabies studied at the Carlos Chagas Hospital of UFMC, State of Minas Gerais, Brazil, from 1963 through 1976. From the epidemioiogical point of view it is concluded that the magnitude of the problem of human rabies in underdeveioped countries remains quite unknown. Speciai emphasis is given to the lack of apropriate knowledge of the recommended preventive measures, and to the influence of health education and socio-economic-cultural structure of the communities. The classic clinical picture of human rabies is briefiy described, particular attention being drawn to psychopathologic features of rabies encephalomyeiitis. it is pointed out that in some cases the mental symptoms may predominate from the onset of the illness, adding difficuity to the diagnosis. According to the Authors, human rabies must be differentiated from several psychopathologic syndromes and also from encephalomyelitis due to other central nervous system infections. It is discussed whether the fataiistic concept of human rabies would be somehow contributing to delay a better understanding of the natural history of the disease.No trabalho são estudados 40 casos de raiva humana identificados no Hospital Carlos Chagas da UFMG, Minas Gerais, Brasil, durante o período compreendido entre 1963 e 1976. Do ponto de vista epidemiológico, concluiu-se que a magnitude do problema gerado pela raiva nos países em desenvolvimento permanece ainda desconhecida. Neste particular, merecem realce o inadequado conhecimento das medidas preventivas recomendadas e a influência de fatores dependentes da educação sanitária e das estruturas sócio-econômica e cultural das comunidades. Descreveu-se sumariamente o quadro clínico clássico da encefalomielite rábica, ressaltando-se suas peculiaridades psicopatológicas. Salientou-se que, em alguns casos, a sintomatologia mental pode predominar desde o início da doença, acarretando dificuldades ao diagn

  14. Determination of oxidation state of iron in normal and pathologically altered human aortic valves

    Energy Technology Data Exchange (ETDEWEB)

    Czapla-Masztafiak, J. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Kraków (Poland); Lis, G.J.; Gajda, M.; Jasek, E. [Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Kraków (Poland); Czubek, U. [Department of Coronary Disease, Jagiellonian University Medical College, John Paul II Hospital, Prądnicka 80, 31-202 Kraków (Poland); Bolechała, F. [Department of Forensic Medicine, Jagiellonian University Medical College, Grzegórzecka 16, 31-531 Kraków (Poland); Borca, C. [Swiss Light Source, Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Kwiatek, W.M. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Kraków (Poland)

    2015-12-01

    In order to investigate changes in chemical state of iron in normal and pathologically altered human aortic valves X-ray absorption spectroscopy was applied. Since Fe is suspected to play detrimental role in aortic valve stenosis pathogenesis the oxidation state of this element has been determined. The experimental material consisted of 10 μm sections of valves excised during routine surgery and from autopsies. The experiment was performed at the MicroXAS beamline of the SLS synchrotron facility in Villigen (Switzerland). The Fe K-edge XANES spectra obtained from tissue samples were carefully analyzed and compared with the spectra of reference compounds containing iron in various chemical structures. The analysis of absorption edge position and shape of the spectra revealed that both chemical forms of iron are presented in valve tissue but Fe{sup 3+} is the predominant form. Small shift of the absorption edge toward higher energy in the spectra from stenotic valve samples indicates higher content of the Fe{sup 3+} form in pathological tissue. Such a phenomenon suggests the role of Fenton reaction and reactive oxygen species in the etiology of aortic valve stenosis. The comparison of pre-edge regions of XANES spectra for control and stenotic valve tissue confirmed no differences in local symmetry or spin state of iron in analyzed samples.

  15. Genetic alteration of poly(ADP-ribose) polymerase-1 in human germ cell tumors.

    Science.gov (United States)

    Shiokawa, Motoko; Masutani, Mitsuko; Fujihara, Hisako; Ueki, Keisuke; Nishikawa, Ryo; Sugimura, Takashi; Kubo, Harumi; Nakagama, Hitoshi

    2005-02-01

    Accumulated evidence suggests that poly(ADP-ribose) polymerase-1 (PARP-1) is involved in DNA repair, cell-death induction, differentiation and tumorigenesis. Parp-1 deficiency also induces trophoblast differentiation from mouse embryonic stem cells during teratocarcinoma-like tumor formation. To understand the relationship of PARP-1 dysfunction and development of germ cell tumors, we conducted a genetic analysis of the PARP-1 gene in human germ cell tumors. Sixteen surgical specimens of germ cell tumors that developed in the brain and testes were used. Two known single nucleotide polymorphisms (SNPs) (Val762Ala and Lys940Arg), which are listed in the SNP database of the NCBI (National Center for Biotechnology Information), were detected. In both cases, cSNPs encoded amino acids located within peptide stretches in the catalytic domain, which are highly conserved among various animal species. Furthermore, another novel sequence alteration, a base change of ATG to ACG, was identified in a tumor specimen, which would result in the amino acid substitution, Met129Thr. This base change was observed in one allele of both tumor and normal tissues, suggesting that it is either a rare SNP or a germline mutation of the PARP-1 gene. Notably, the amino acid Met129 is located within the second zinc finger domain, which is essential for DNA binding and is conserved among animal species. One SNP in intron 2 and one in the upstream 5'-UTR (untranslated region) were also detected.

  16. Shielding of the Geomagnetic Field Alters Actin Assembly and Inhibits Cell Motility in Human Neuroblastoma Cells.

    Science.gov (United States)

    Mo, Wei-Chuan; Zhang, Zi-Jian; Wang, Dong-Liang; Liu, Ying; Bartlett, Perry F; He, Rong-Qiao

    2016-03-31

    Accumulating evidence has shown that absence of the geomagnetic field (GMF), the so-called hypomagnetic field (HMF) environment, alters the biological functions in seemingly non-magnetosensitive cells and organisms, which indicates that the GMF could be sensed by non-iron-rich and non-photo-sensing cells. The underlying mechanisms of the HMF effects on those cells are closely related to their GMF sensation but remain poorly understood so far. Previously, we found that the HMF represses expressions of genes associated with cell migration and cytoskeleton assembly in human neuroblastoma cells (SH-SY5Y cell line). Here, we measured the HMF-induced changes on cell morphology, adhesion, motility and actin cytoskeleton in SH-SY5Y cells. The HMF inhibited cell adhesion and migration accompanied with a reduction in cellular F-actin amount. Moreover, following exposure to the HMF, the number of cell processes was reduced and cells were smaller in size and more round in shape. Furthermore, disordered kinetics of actin assembly in vitro were observed during exposure to the HMF, as evidenced by the presence of granule and meshed products. These results indicate that elimination of the GMF affects assembly of the motility-related actin cytoskeleton, and suggest that F-actin is a target of HMF exposure and probably a mediator of GMF sensation.

  17. Metabolic alterations in the human erythrocyte produced by increases in glucose concentration

    Science.gov (United States)

    Travis, Susan F.; Morrison, Anthony D.; Clements, Rex S.; Winegrad, Albert I.; Oski, Frank A.

    1971-01-01

    Human erythrocytes incubated in medium containing 50 mM glucose have increased intracellular sorbitol and fructose concentrations as compared with samples incubated with 5 mM glucose. Increased medium glucose concentration did not significantly alter total glucose consumption or lactate production. However, the intracellular lactate:pyruvate ratio rose, the concentrations of fructose diphosphate, and triose phosphates increased, and the 2,3-diphosphoglycerate concentration fell. [14C]O2 production from glucose-1-14C also increased with increased medium glucose concentration. These changes are believed to reflect changes in the redox states of the diphosphopyridine nucleotide/reduced form of diphosphopyridine nucleotide (NAD/NADH) and nicotinamide—adenine dinucleotide phosphate/reduced form of nicotinamide—adenine dinucleotide phosphate (NADP/NADPH) couples resulting from increased activity of the polyol pathway. Addition of pyruvate to the incubation media prevented these changes. These studies illustrate that an increase in the red cell's normal substrate, glucose, can produce changes in red cell metabolism. PMID:4398937

  18. Nicotine alters MicroRNA expression and hinders human adult stem cell regenerative potential.

    Science.gov (United States)

    Ng, Tsz Kin; Carballosa, Carlos M; Pelaez, Daniel; Wong, Hoi Kin; Choy, Kwong Wai; Pang, Chi Pui; Cheung, Herman S

    2013-03-01

    Adult stem cells are critical for the healing process in regenerative medicine. However, cigarette smoking inhibits stem cell recruitment to tissues and delays the wound-healing process. This study investigated the effect of nicotine, a major constituent in the cigarette smoke, on the regenerative potentials of human mesenchymal stem cells (MSC) and periodontal ligament-derived stem cells (PDLSC). The cell proliferation of 1.0 μM nicotine-treated MSC and PDLSC was significantly reduced when compared to the untreated control. Moreover, nicotine also retarded the locomotion of these adult stem cells. Furthermore, their osteogenic differentiation capabilities were reduced in the presence of nicotine as evidenced by gene expression (RUNX2, ALPL, BGLAP, COL1A1, and COL1A2), calcium deposition, and alkaline phosphatase activity analyses. In addition, the microRNA (miRNA) profile of nicotine-treated PDLSC was altered; suggesting miRNAs might play an important role in the nicotine effects on stem cells. This study provided the possible mechanistic explanations on stem cell-associated healing delay in cigarette smoking.

  19. Alterations of expression and regulation of transforming growth factor beta in human cancer prostate cell lines.

    Science.gov (United States)

    Blanchère, M; Saunier, E; Mestayer, C; Broshuis, M; Mowszowicz, I

    2002-11-01

    TGF beta can promote and/or suppress prostate tumor growth through multiple and opposing actions. Alterations of its expression, secretion, regulation or of the sensitivity of target cells can lead to a favorable environment for tumor development. To gain a better insight in TGF beta function during cancer progression, we have used different cultured human prostate cells: preneoplastic PNT2 cells, the androgen-dependent LNCaP and the androgen-independent PC3 and DU145 prostate cancer cell lines. We have studied by specific ELISA assays in conditioned media (CM), the secretion of TGF beta 1 and TGF beta 2 in basal conditions and after hormonal treatment (DHT or E2) and the expression of TGF beta 1 mRNA by Northern blot. We have also compared the effect of fibroblast CM on TGF beta secretion by the different cell types. Compared to PNT2 cells, cancer cell lines secrete lower levels of active TGF beta which are not increased in the presence of fibroblast CM. LNCaP cells respond to androgen or estrogen treatment by a 10-fold increase of active TGF beta secretion while PC3 and DU145 are unresponsive. In conclusion, prostate cancer cell lines have lost part of their ability to secrete and activate TGF beta, and to regulate this secretion through stromal-epithelial interactions. Androgen-sensitive cancer cells may compensate this loss by hormonal regulation.

  20. Urine proteomes of healthy aging humans reveal extracellular matrix (ECM) alterations and immune system dysfunction.

    Science.gov (United States)

    Bakun, M; Senatorski, G; Rubel, T; Lukasik, A; Zielenkiewicz, P; Dadlez, M; Paczek, L

    2014-02-01

    Aging is a complex physiological process that poses considerable conundrums to rapidly aging societies. For example, the risk of dying from cardiovascular diseases and/or cancer steadily declines for people after their 60s, and other causes of death predominate for seniors older than 80 years of age. Thus, physiological aging presents numerous unanswered questions, particularly with regard to changing metabolic patterns. Urine proteomics analysis is becoming a non-invasive and reproducible diagnostic method. We investigated the urine proteomes in healthy elderly people to determine which metabolic processes were weakened or strengthened in aging humans. Urine samples from 37 healthy volunteers aged 19-90 years (19 men, 18 women) were analyzed for protein expression by liquid chromatography-tandem mass spectrometry. This generated a list of 19 proteins that were differentially expressed in different age groups (young, intermediate, and old age). In particular, the oldest group showed protein changes reflective of altered extracellular matrix turnover and declining immune function, in which changes corresponded to reported changes in cardiovascular tissue remodeling and immune disorders in the elderly. Thus, urinary proteome changes in the elderly appear to reflect the physiological processes of aging and are particularly clearly represented in the circulatory and immune systems. Detailed identification of "protein trails" creates a more global picture of metabolic changes that occur in the elderly.

  1. Expression of human dopamine receptor in potato (Solanum tuberosum results in altered tuber carbon metabolism

    Directory of Open Access Journals (Sweden)

    Świędrych Anna

    2005-02-01

    Full Text Available Abstract Background Even though the catecholamines (dopamine, norepinephrine and epinephrine have been detected in plants their role is poorly documented. Correlations between norepinephrine, soluble sugars and starch concentration have been recently reported for potato plants over-expressing tyrosine decarboxylase, the enzyme mediating the first step of catecholamine synthesis. More recently norepinephrine level was shown to significantly increase after osmotic stress, abscisic acid treatment and wounding. Therefore, it is possible that catecholamines might play a role in plant stress responses by modulating primary carbon metabolism, possibly by a mechanism similar to that in animal cells. Since to date no catecholamine receptor has been identified in plants we transformed potato plants with a cDNA encoding human dopamine receptor (HD1. Results Tuber analysis of transgenic plants revealed changes in the activities of key enzymes mediating sucrose to starch conversion (ADP-glucose phosphorylase and sucrose synthase and sucrose synthesis (sucrose phosphate synthase leading to altered content of both soluble sugars and starch. Surprisingly the catecholamine level measured in transgenic plants was significantly increased; the reason for this is as yet unknown. However the presence of the receptor affected a broader range of enzyme activities than those affected by the massive accumulation of norepinephrine reported for plants over-expressing tyrosine decarboxylase. Therefore, it is suggested that the presence of the exogenous receptor activates catecholamine cAMP signalling in plants. Conclusions Our data support the possible involvement of catecholamines in regulating plant carbon metabolism via cAMP signalling pathway.

  2. Distribution of human papillomavirus genotypes in women with cervical alterations from north Argentina

    Directory of Open Access Journals (Sweden)

    G D Deluca

    2013-01-01

    Full Text Available Background: Cervical cancer remains a major public health problem in northern Argentina, showing the highest mortality rate in the country (approximately 22 cases/100000 women. Objective: The aim of this study was to provide epidemiological data on the prevalence and type distribution of human papillomavirus (HPV in women with pre-neoplastic lesions before the massive introduction of HPV vaccination in the country. Materials and Methods: Exfoliated cervical cells were collected to screen for HPV using the widely known MY09/11 PCR, followed by the restriction fragment-length polymorphism (RFLP technique from a total of 714 women with previously diagnosed atypical squamous cells of undetermined significance (ASCUS, low-grade squamous intraepithelial lesion (LG-SIL and high-grade squamous intraepithelial lesion (HG-SIL. Results: Overall HPV prevalence was 48.2% in ASCUS (24 different HPV types detected, 66.5% in LG-SIL (37 HPV types detected and 82.6% in HG-SIL (16 HPV types detected. HPV-16 was the most prevalent type among all cases. With respect to multiple HPV infections, 9.6% were observed in ASCUS, 14.3% in LG-SIL and 11.4% in HG-SIL. Conclusion: The major strength of our study is the assessment of a large series of women with cytological alterations in this region. The information attained will be useful as a regional baseline for future epidemiological vigilance, in the context of the national HPV vaccination program.

  3. Morphologic alterations in the epithelium of the human oviduct induced by a low dosis gestagen.

    Science.gov (United States)

    Spornitz, U M; Ludwig, K S; Mall-Haefeli, M

    1977-11-29

    Morphological alterations in the epithelium of the human oviduct related to continuous administration of low dosage lynestrenol were studied in 10 women by electron microscopy. The effect of lynestrenol on the morphology of the tubal epithelium was shown to be time dependent. First the discharge of secretory products from the non-ciliated cells was inhibited. Secondary to this the synthetic activities of the cells were drastically decreased. This inactivation of the tubal epithelium reached its maximum after 6 months. At this time the epithelial cells, particularly the non-ciliated cells were almost devoid of organelles and had an electron transparent cytoplasm. In addition to the action of lynestrenol on the secretory and synthetic activities of the cells a strong ciliogenetic effect could be observed after about 3 months of lynestrenol administration. The ratio of ciliated to non-ciliated cells changed from 1:1 at the beginning of the treatment to 2.9:1 after 6 months. This ratio was then maintained and could still be found in patients who had used lynestrenol for 25 and 39 months. In contrast to the persistent effect of lynestrenol on the ciliary apparatus of the cells the synthetic activities and the secretory mechanism were partially restored with long standing use. The importance of the observed changes and their possible participation in the contraceptive action of lynestrenol are discussed.

  4. Acute experimental endotoxemia induces visceral hypersensitivity and altered pain evaluation in healthy humans.

    Science.gov (United States)

    Benson, Sven; Kattoor, Joswin; Wegner, Alexander; Hammes, Florian; Reidick, Daniel; Grigoleit, Jan-Sebastian; Engler, Harald; Oberbeck, Reiner; Schedlowski, Manfred; Elsenbruch, Sigrid

    2012-04-01

    Growing evidence suggests that systemic immune activation plays a role in the pathophysiology of pain in functional bowel disorders. By implementing a randomized crossover study with an injection of endotoxin or saline, we aimed to test the hypothesis that endotoxin-induced systemic inflammation increases visceral pain sensitivity in humans. Eleven healthy men (mean ± standard error of the mean age 26.6 ± 1.1 years) received an intravenous injection of either lipopolysaccharide (LPS; 0.4 ng/kg) or saline on 2 otherwise identical study days. Blood samples were collected 15 min before and 1, 2, 3, 4, and 6h after injection to characterize changes in immune parameters including proinflammatory cytokines. Rectal sensory and pain thresholds and subjective pain ratings were assessed with barostat rectal distensions 2h after injection. LPS administration induced an acute inflammatory response indicated by transient increases in tumor necrosis factor alpha, interleukin 6, and body temperature (all Pvisceral sensory and pain thresholds (both PVisceral stimuli were rated as more unpleasant (PPain thresholds correlated with interleukin 6 at +1h (r=0.60, Pvisceral sensory and pain thresholds and altered subjective pain ratings. Our results support the relevance of inflammatory processes in the pathophysiology of visceral hyperalgesia and underscore the need for studies to further elucidate immune-to-brain communication pathways in gastrointestinal disorders. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  5. Disturbed mitochondrial function restricts glutamate uptake in the human Müller glia cell line, MIO-M1

    DEFF Research Database (Denmark)

    Vohra, Rupali; Gurubaran, Iswariyaraja Sridevi; Henriksen, Ulrik Birk

    2017-01-01

    Using the human Müller cell line, MIO-M1, the aim was to study the impact of mitochondrial inhibition in Müller glia through antimycin A treatment. MIO-M1 cell survival, levels of released lactate, mitochondrial function, and glutamate uptake were studied in response to mitochondrial inhibition...... inhibition caused impaired glutamate uptake and decreased mRNA expression of the glutamate transporter, EAAT1. Over all, we show important roles of mitochondrial activity in MIO-M1 cell function and survival....

  6. Release of tensile strain on engineered human tendon tissue disturbs cell adhesions, changes matrix architecture, and induces an inflammatory phenotype

    DEFF Research Database (Denmark)

    Bayer, Monika L; Schjerling, Peter; Herchenhan, Andreas

    2014-01-01

    -inflammatory mediators and tendon phenotypic specific molecules, in an in vitro model where tendon-like tissue was engineered from human tendon cells. Tissue sampling was performed 1, 2, 4 and 6 days after surgical de-tensioning of the tendon construct. When tensile stimulus was removed, integrin type collagen receptors...... were upregulated. Stimulation with the cytokine TGF-β1 had distinct effects on some tendon-related genes in both tensioned and de-tensioned tissue. These findings indicate an important role of mechanical loading for cellular and matrix responses in tendon, including that loss of tension leads...

  7. Analysis of Human Disturbance and Ecological Security Evolution in Oasis in Arid Area Based on LUCC: A Case Study of Oasis in the Northern Tianshan Mountain Slope Economic Zone

    Science.gov (United States)

    Song, W. J.; Chen, M. H.; Zhang, Q.; Liu, S. S.; Yang, J. N.

    2017-07-01

    Oases in arid areas are environmentally and economically vulnerable regions. Study on ecological security of oases in arid areas is of great significance to the stability and the economic development of oases. Based on Land Use/Land Cover data in 1965, 1980, 1995, 2005 and 2015, the study analyze the temporal and spatial changes in human disturbance and ecological security of oases in the Northern Tianshan Mountain Slope Economic Zone (NTMSEZ) in recent 50 years by establishing the ecological security index (ESI) through human disturbance index and landscape vulnerability index. The results showed that: in recent 50 years, the human disturbance of the NTMSEZ has been increased to current moderate human impacts. Urban construction, oasis expansion and farmland reclamation are the main factors of the increment. The human disturbance in Urumchi, Shihezi, Kuitun, Miquan and Changji is higher than that in other oases and that in core areas of oasis is higher than other areas. The ESI of the NTMSEZ increases firstly and then decreases. In most areas, the ESI is “relatively unsafe” and “critical”. However, there are increasingly more vulnerable areas, moving northwestwards and expanding southwards. The ESI gradually presents a “NW-SE” trend of zonal distribution pattern.

  8. High glucose concentrations alter the biomineralization process in human osteoblastic cells.

    Science.gov (United States)

    García-Hernández, A; Arzate, H; Gil-Chavarría, I; Rojo, R; Moreno-Fierros, L

    2012-01-01

    Diabetes mellitus (DM) may alter bone remodeling, as osteopenia and osteoporosis are among the complications. Moreover, DM increases the risk and severity of chronic inflammatory periodontal disease, in which bone resorption occurs. Broad evidence suggests that chronic inflammation can contribute to the development of DM and its complications. Hyperglycemia is a hallmark of DM that may contribute to sustained inflammation by increasing proinflammatory cytokines, which are known to cause insulin resistance, via toll-like receptor (TLR)-4-mediated mechanisms. However, the mechanisms by which bone-related complications develop in DM are still unknown. Studies done on the effect of high glucose concentrations on osteoblast functions are contradictory because some suggest increases (although others suggest reductions) in the biomineralization process. Therefore, we evaluated the effect of high glucose levels on biomineralization and inflammation markers in a human osteoblastic cell line. Cells were treated with either physiological 5.5 mM or increasing concentrations of glucose up to 24 mM, and we determined the following: i) the quantity and quality of calcium-deposit crystals in culture and ii) the expression of the following: a) proteins associated with the process of biomineralization, b) the receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG), c) cytokines IL1, IL6, IL8, IL10, MCP-1 and TNF alpha, and d) TLR-2, -3, -4 and -9. Our results show that high glucose concentrations (12 mM and particularly 24 mM) alter the biomineralization process in osteoblastic cells and provoke the following: i) a rise in mineralization, ii) an increase in the mRNA expression of RANKL and a decrease of OPG, iii) an increase in the mRNA expression of osteocalcin, bone sialoprotein and the transcription factor Runx2, iv) a diminished quality of the mineral, and v) an increase in the expression of IL1beta, IL6, IL8, MCP-1 and IL10 mRNAs. In addition we

  9. Flow cytometry of cerebrospinal fluid (CSF) lymphocytes: alterations of blood/CSF ratios of lymphocyte subsets in inflammation disorders of human central nervous system (CNS).

    Science.gov (United States)

    Kleine, T O; Albrecht, J; Zöfel, P

    1999-03-01

    Flow cytometry was adapted to measure lymphocytes in human cerebrospinal fluid (CSF). The method was sufficiently precise, reproducible and accurate despite low cell counts. In lumbar CSF of controls with 500 to 3500 (10(3)/l) leukocytes, lymphocyte counts correlated with those in corresponding venous blood: blood/CSF ratios of approximately 2000 : 1 were found for total T cells (CD3+) and CD3+ HLA-DR-, CD3+4+, CD3+8+ subsets, ratios were increased for the lymphocyte subsets CD3+ HLA-DR+ blood-brain and blood-CSF barriers) to blood lymphocyte subsets which favor the transfer of T subsets. Correlation of the subset ratios to the CD3+ ratio indicates distinct barrier properties which changed differently with acute and subacute inflammations and neuroimmunological diseases of central nervous system (CNS) in lumbar or ventricular CSF, but not with simple protein barrier disturbance. HLA DR+ T ratios were higher than HLA DR- T ratios only with controls and some neuroimmunological diseases. Lymphocyte barrier characteristics were related to protein leakage situated at the same barriers, indicating for the lymphocyte subsets selective transfer routes in control subjects and non-selective routes in patients with CNS inflammation where altered ratios revealed a mixture of both routes.

  10. Disturbed mitochondrial function restricts glutamate uptake in the human Müller glia cell line, MIO-M1.

    Science.gov (United States)

    Vohra, Rupali; Gurubaran, Iswariyaraja Sridevi; Henriksen, Ulrik; Bergersen, Linda Hildegaard; Rasmussen, Lene Juel; Desler, Claus; Skytt, Dorte Marie; Kolko, Miriam

    2017-09-01

    Using the human Müller cell line, MIO-M1, the aim was to study the impact of mitochondrial inhibition in Müller glia through antimycin A treatment. MIO-M1 cell survival, levels of released lactate, mitochondrial function, and glutamate uptake were studied in response to mitochondrial inhibition and glucose restriction. Lactate release decreased in response to glucose restriction. Combined glucose restriction and blocked mitochondrial activity decreased survival and caused collapse of the respiratory chain measured by oxygen consumption rate and extracellular acidification rate. Mitochondrial inhibition caused impaired glutamate uptake and decreased mRNA expression of the glutamate transporter, EAAT1. Over all, we show important roles of mitochondrial activity in MIO-M1 cell function and survival. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  11. Alteration of gene expression in human cells treated with the agricultural chemical diazinon: possible interaction in fetal development.

    Science.gov (United States)

    Mankame, T; Hokanson, R; Fudge, R; Chowdhary, R; Busbee, D

    2006-05-01

    Agricultural chemicals frequently alter human health or development, typically because they have endocrine agonist or antagonist activities and alter hormone-regulation of gene expression. The insecticide, diazinon, was evaluated for gene expression disrupting activity using MCF-7 cells, an estrogen-dependent human cell line, to examine the capacity of the insecticide to disrupt gene expression essential for morphological development, immune system development or function, and/or central nervous system development and function. MCF-7 cells were treated with 30, 50 or 67 ppm diazinon, and gene expression was measured in treated cells compared to expression in untreated or estrogen-treated cells. DNA microarray analysis of diazinon-treated cells showed significant up- or down-regulation of a large number of genes compared to untreated cells. Of the 600 human genes on the Phase 1 chip utilized for these studies, two specific genes--calreticulin and TGF-beta3--were selected for corroboration using quantitative real time PCR (qrtPCR). qrtPCR, completed to assess gene expression levels for calreticulin and TGFbeta3, confirmed results showing significant up-regulation of these two genes obtained from the microarray data. These studies were designed to provide baseline data on the gene expression-altering capacity of a specific chemical, diazinon, and allow a partial assessment of the potentially deleterious effects associated with exposure of human cells to this chemical. Currently, it is not known whether results from cells in vitro can be extrapolated to human health consequences of chemical exposure.

  12. Human brain plasticity: evidence from sensory deprivation and altered language experience.

    Science.gov (United States)

    Neville, Helen; Bavelier, Daphne

    2002-01-01

    The results from the language studies taken as a whole point to different developmental time courses and developmental vulnerabilities of aspects of grammatical and semantic/lexical processing. They thus provide support for conceptions of language that distinguish these subprocesses within language. Similarly, following auditory deprivation, processes associated with the dorsal visual pathway were more altered than were functions associated with the ventral pathway, providing support for conceptions of visual system organization that distinguish functions along these lines. Could the effects observed in blind and deaf adults be accounted for, at least in part, by the redundant connectivity of the immature human brain? One way we tested this hypothesis was to study the differentiation of visual and auditory sensory responses in normal development (Neville, 1995). In normal adults, auditory stimuli elicit ERP responses that are large over temporal brain regions but small or absent over occipital regions. By contrast, in 6-month-old children we observed that auditory ERPs are equally large over temporal and visual brain regions, consistent with the idea that there is less specificity and more redundancy of connections between the auditory and visual cortex at this time. Between 6 and 36 months, however, we observed a gradual decrease in the amplitude of the auditory ERP over visual areas, while the amplitude over the temporal areas was unchanged. These results suggest that early in human development, there exists a redundancy of connections between auditory and visual areas and that this overlap gradually decreases after birth. This loss of redundancy may be a boundary condition that determines when sensory deprivation can result in alterations in the organization of remaining sensory systems. The considerable variability in timing of sensitive periods may also be in part due to temporal differences in the occurrence of redundancy within different systems. Ongoing

  13. [Methylenebisphosphonic acid alters the pattern of pericellular glycosaminoglycans and binding properties of CD44 in human endothelial cells].

    Science.gov (United States)

    Ievdokymova, N Iu; Karlova, N P; Baranova, N S; Komisarenko, S V

    2006-01-01

    The effect of methylenebisphosphonic acid (MBPA) on glycosaminoglycan metabolism, adhesive and proliferative properties of human endothelial cells has been investigated. It was demonstrated that MBPA (100 microM) inhibited the synthesis of all studied groups of glycosaminoglycans, but promoted the accumulation of heparan sulphate in endothelial pericellular matrix. Simultaneously, the redistribution of hyaluronic acid from pericellular matrix to the conditioned medium was observed. The decreased adhesion of endothelial cells to immobilized hyaluronic acid was not mediated by the alterations of CD44 expression. It was also demonstrated that MBPA affected the proliferative properties of endothelial cells. The alterations of glycosaminoglycan metabolism are considered to be involved in antiangiogenic effects of MBPA.

  14. Polychlorinated biphenyls disturb differentiation of normal human neural progenitor cells: clue for involvement of thyroid hormone receptors.

    Science.gov (United States)

    Fritsche, Ellen; Cline, Jason E; Nguyen, Ngoc-Ha; Scanlan, Thomas S; Abel, Josef

    2005-07-01

    Polychlorinated biphenyls (PCBs) are ubiquitous environmental chemicals that accumulate in adipose tissues over the food chain. Epidemiologic studies have indicated that PCBs influence brain development. Children who are exposed to PCBs during development suffer from neuropsychologic deficits such as a lower full-scale IQ (intelligence quotient), reduced visual recognition memory, and attention and motor deficits. The mechanisms leading to these effects are not fully understood. It has been speculated that PCBs may affect brain development by interfering with thyroid hormone (TH) signaling. Because most of the data are from animal studies, we established a model using primary normal human neural progenitor (NHNP) cells to determine if PCBs interfere with TH-dependent neural differentiation. NHNP cells differentiate into neurons, astrocytes, and oligodendrocytes in culture, and they express a variety of drug metabolism enzymes and nuclear receptors. Like triiodothyronine (T3), treatment with the mono-ortho-substituted PCB-118 (2,3',4,4 ,5-pentachlorobiphenyl; 0.01-1 microM) leads to a dose-dependent increase of oligodendrocyte formation. This effect was congener specific, because the coplanar PCB-126 (3,3',4,4 ,5-pentachlorobiphenyl) had no effect. Similar to the T3 response, the PCB-mediated effect on oligodendrocyte formation was blocked by retinoic acid and the thyroid hormone receptor antagonist NH-3. These results suggest that PCB-118 mimics T3 action via the TH pathway.

  15. Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis.

    Science.gov (United States)

    Luckert, Claudia; Hessel, Stefanie; Lenze, Dido; Lampen, Alfonso

    2015-10-01

    1,2-unsaturated pyrrolizidine alkaloids (PA) are plant metabolites predominantly occurring in the plant families Asteraceae and Boraginaceae. Acute and chronic PA poisoning causes severe hepatotoxicity. So far, the molecular mechanisms of PA toxicity are not well understood. To analyze its mode of action, primary human hepatocytes were exposed to a non-cytotoxic dose of 100 μM of four structurally different PA: echimidine, heliotrine, senecionine, senkirkine. Changes in mRNA expression were analyzed by a whole genome microarray. Employing cut-off values with a |fold change| of 2 and a q-value of 0.01, data analysis revealed numerous changes in gene expression. In total, 4556, 1806, 3406 and 8623 genes were regulated by echimidine, heliotrine, senecione and senkirkine, respectively. 1304 genes were identified as commonly regulated. PA affected pathways related to cell cycle regulation, cell death and cancer development. The transcription factors TP53, MYC, NFκB and NUPR1 were predicted to be activated upon PA treatment. Furthermore, gene expression data showed a considerable interference with lipid metabolism and bile acid flow. The associated transcription factors FXR, LXR, SREBF1/2, and PPARα/γ/δ were predicted to be inhibited. In conclusion, though structurally different, all four PA significantly regulated a great number of genes in common. This proposes similar molecular mechanisms, although the extent seems to differ between the analyzed PA as reflected by the potential hepatotoxicity and individual PA structure.

  16. Locomotor training alters the behavior of flexor reflexes during walking in human spinal cord injury.

    Science.gov (United States)

    Smith, Andrew C; Mummidisetty, Chaithanya K; Rymer, William Zev; Knikou, Maria

    2014-11-01

    In humans, a chronic spinal cord injury (SCI) impairs the excitability of pathways mediating early flexor reflexes and increases the excitability of late, long-lasting flexor reflexes. We hypothesized that in individuals with SCI, locomotor training will alter the behavior of these spinally mediated reflexes. Nine individuals who had either chronic clinically motor complete or incomplete SCI received an average of 44 locomotor training sessions. Flexor reflexes, elicited via sural nerve stimulation of the right or left leg, were recorded from the ipsilateral tibialis anterior (TA) muscle before and after body weight support (BWS)-assisted treadmill training. The modulation pattern of the ipsilateral TA responses following innocuous stimulation of the right foot was also recorded in 10 healthy subjects while they stepped at 25% BWS to investigate whether body unloading during walking affects the behavior of these responses. Healthy subjects did not receive treadmill training. We observed a phase-dependent modulation of early TA flexor reflexes in healthy subjects with reduced body weight during walking. The early TA flexor reflexes were increased at heel contact, progressively decreased during the stance phase, and then increased throughout the swing phase. In individuals with SCI, locomotor training induced the reappearance of early TA flexor reflexes and changed the amplitude of late TA flexor reflexes during walking. Both early and late TA flexor reflexes were modulated in a phase-dependent pattern after training. These new findings support the adaptive capability of the injured nervous system to return to a prelesion excitability and integration state. Copyright © 2014 the American Physiological Society.

  17. Acute stress alters auditory selective attention in humans independent of HPA: a study of evoked potentials.

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    Ludger Elling

    Full Text Available BACKGROUND: Acute stress is a stereotypical, but multimodal response to a present or imminent challenge overcharging an organism. Among the different branches of this multimodal response, the consequences of glucocorticoid secretion have been extensively investigated, mostly in connection with long-term memory (LTM. However, stress responses comprise other endocrine signaling and altered neuronal activity wholly independent of pituitary regulation. To date, knowledge of the impact of such "paracorticoidal" stress responses on higher cognitive functions is scarce. We investigated the impact of an ecological stressor on the ability to direct selective attention using event-related potentials in humans. Based on research in rodents, we assumed that a stress-induced imbalance of catecholaminergic transmission would impair this ability. METHODOLOGY/PRINCIPAL FINDINGS: The stressor consisted of a single cold pressor test. Auditory negative difference (Nd and mismatch negativity (MMN were recorded in a tonal dichotic listening task. A time series of such tasks confirmed an increased distractibility occurring 4-7 minutes after onset of the stressor as reflected by an attenuated Nd. Salivary cortisol began to rise 8-11 minutes after onset when no further modulations in the event-related potentials (ERP occurred, thus precluding a causal relationship. This effect may be attributed to a stress-induced activation of mesofrontal dopaminergic projections. It may also be attributed to an activation of noradrenergic projections. Known characteristics of the modulation of ERP by different stress-related ligands were used for further disambiguation of causality. The conjuncture of an attenuated Nd and an increased MMN might be interpreted as indicating a dopaminergic influence. The selective effect on the late portion of the Nd provides another tentative clue for this. CONCLUSIONS/SIGNIFICANCE: Prior studies have deliberately tracked the adrenocortical influence

  18. Altered aquaporin-4 expression in human muscular dystrophies: a common feature?

    Science.gov (United States)

    Frigeri, Antonio; Nicchia, Grazia Paola; Repetto, Silvia; Bado, Massimo; Minetti, Carlo; Svelto, Maria

    2002-07-01

    Duchenne Muscular Dystrophy (DMD) is a progressive lethal muscle disease that affects young boys. Dystrophin, absent in DMD and reduced in the milder form Becker Muscular Dystrophy (BMD), binds to several membrane-associated proteins known as dystrophin-associated proteins (DAPs). Once this critical structural link is disrupted, muscle fibers become more vulnerable to mechanical and osmotic stress. Recently, we have reported that the expression of aquaporin-4 (AQP4), a water-selective channel expressed in the sarcolemma of fast-twitch fibers and astrocyte end-feet, is drastically reduced in the muscle and brain of the mdx mouse, the animal model of DMD. In the present study, we analyzed the expression of AQP4 in several DMD/BMD patients of different ages with different mutations in the dystrophin gene. Immunofluorescence results indicate that, compared with healthy control children, AQP4 is reduced severely in all the DMD muscular biopsies analyzed and in 50% of the analyzed BMD. Western blot analysis revealed that the deficiency in sarcolemma AQP4 staining is due to a reduction in total AQP4 muscle protein content rather than to changes in immunoreactivity. Double-immunostaining experiments indicate that AQP4 reduction is independent of changes in the fiber myosin heavy chain composition. AQP4 and a-syntrophin analysis of BMD muscular biopsies revealed that the expression and stability of AQP4 in the sarcolemma does not always decrease when a-syntrophin is strongly reduced. Finally, limb-girdle muscular dystrophy biopsies and facioscapulohumeral muscular dystrophy revealed that AQP4 expression was not altered in these forms of muscular dystrophy. These experiments provide the first evidence of AQP4 reduction in a human pathology and show that this deficiency is an important feature of DMD/BMD.

  19. Baseflow mean transit times in natural and human-altered catchments

    Science.gov (United States)

    Boll, J.; Sanchez-Murillo, R.; Brooks, E. S.; Elliot, W. E.

    2013-12-01

    Baseflow is one of the most important components of the ecosystem since it provides continuous habitat to aquatic biota; regulates water chemistry, temperature, and dissolved oxygen during summer; and functions as an essential supply for drinking water and food production worldwide. This study will evaluate baseflow mean transit times (MTTs) in five natural (i.e. pristine forest) and human-altered (i.e. agricultural, urban, and mining) catchments in eastern Washington and northern Idaho during 2011-2013. Drainage area ranges from small (6.35 km2) to meso scale (342 km2) and mean annual precipitation varies from 670 mm to 1,313 mm. MTTs were evaluated by applying d18O input precipitation and output stream waters to a lumped parameter model (FlowPC 3.2) using four main theoretical distribution models: piston flow, exponential, dispersion, and piston-exponential. Precipitation samples (N=307) were collected on weekly to biweekly basis and stream samples (N=690) were collected weekly using automated samplers. Precipitation showed a strong seasonal periodicity with a sine-wave modeled amplitude of 3.03‰ and a mean annual average of d18O= -15.13‰. Mean annual stream d18O ranged from -14.87‰ to -15.80‰ across the study catchments. Our modeling results will show information for examining solute transport and water availability under current and future land use practices and climate variability within a variety of watersheds in the inland Pacific Northwest that share similar underlying geology and climate attributes.

  20. Shear Stress-Induced Alteration of Epithelial Organization in Human Renal Tubular Cells.

    Directory of Open Access Journals (Sweden)

    Damien Maggiorani

    Full Text Available Tubular epithelial cells in the kidney are continuously exposed to urinary fluid shear stress (FSS generated by urine movement and recent in vitro studies suggest that changes of FSS could contribute to kidney injury. However it is unclear whether FSS alters the epithelial characteristics of the renal tubule. Here, we evaluated in vitro and in vivo the influence of FSS on epithelial characteristics of renal proximal tubular cells taking the organization of junctional complexes and the presence of the primary cilium as markers of epithelial phenotype. Human tubular cells (HK-2 were subjected to FSS (0.5 Pa for 48 h. Control cells were maintained under static conditions. Markers of tight junctions (Claudin-2, ZO-1, Par polarity complex (Pard6, adherens junctions (E-Cadherin, β-Catenin and the primary cilium (α-acetylated Tubulin were analysed by quantitative PCR, Western blot or immunocytochemistry. In response to FSS, Claudin-2 disappeared and ZO-1 displayed punctuated and discontinuous staining in the plasma membrane. Expression of Pard6 was also decreased. Moreover, E-Cadherin abundance was decreased, while its major repressors Snail1 and Snail2 were overexpressed, and β-Catenin staining was disrupted along the cell periphery. Finally, FSS subjected-cells exhibited disappeared primary cilium. Results were confirmed in vivo in a uninephrectomy (8 months mouse model where increased FSS induced by adaptive hyperfiltration in remnant kidney was accompanied by both decreased epithelial gene expression including ZO-1, E-cadherin and β-Catenin and disappearance of tubular cilia. In conclusion, these results show that proximal tubular cells lose an important number of their epithelial characteristics after long term exposure to FSS both in vitro and in vivo. Thus, the changes in urinary FSS associated with nephropathies should be considered as potential insults for tubular cells leading to disorganization of the tubular epithelium.

  1. Alterations of T-cell surface markers in older women with persistent human papillomavirus infection

    Science.gov (United States)

    Rodríguez, Ana Cecilia; García-Piñeres, Alfonso J; Hildesheim, Allan; Herrero, Rolando; Trivett, Matthew; Williams, Marcus; Atmella, Ivannia; Ramírez, Margarita; Villegas, Maricela; Schiffman, Mark; Burk, Robert; Freer, Enrique; Bonilla, José; Bratti, Concepción; Pinto, Ligia A

    2012-01-01

    We previously reported decreased lymphocyte proliferative responses among older women with persistent human papillomavirus (HPV) infection. To characterize the phenotype of peripheral lymphocytes associated with persistent HPV infection, we evaluated the expression of different cell surface markers in peripheral blood mononuclear cells (PBMCs) from a case-control study within a 10,049-woman population-based cohort study in Guanacaste, Costa Rica. Women in the cohort aged 46 to 74 and with HPV results at their 5th year anniversary visit were considered, and all women (n=87) with persistent HPV infections, all women (n=196) with transient HPV infections and a random sample of HPV DNA-negative women (n=261) frequency-matched to cases on age were selected for this study. A median of 3 years after the case-control matching visit, cervical cells were collected for liquid-based cytology and repeat HPV DNA genotyping. Blood was obtained from which PBMCs were extracted and cryopreserved for immunological phenotyping via flow cytometry. Significant increases in risk of HPV persistence were observed for three marker subsets indicative of immune cell activation/differentiation. Relative risk estimates were 5.4 (95%CI=2.2–13.3) for CD69+CD4+, 2.6 (95%CI=1.2–5.9) for HLADR+CD3+CD4+ and 2.3 (95%CI=1.1–4.7) for CD45RO+CD27−CD8+. A significant decrease in HPV persistence was observed for a subset marker indicative of an immature, undifferentiated memory state CD45RO+CD27+CD4+ (OR=0.36; 95%CI = 0.17–0.76). Adjustment for these markers only partially explained the previously reported association between decreased lymphoproliferative responses and persistent HPV infection. Whether phenotypic alterations observed predispose to HPV persistence or result from it should be the focus of future studies. PMID:20473864

  2. Bordetella pertussis naturally occurring isolates with altered lipooligosaccharide structure fail to fully mature human dendritic cells.

    Science.gov (United States)

    Brummelman, Jolanda; Veerman, Rosanne E; Hamstra, Hendrik Jan; Deuss, Anna J M; Schuijt, Tim J; Sloots, Arjen; Kuipers, Betsy; van Els, Cécile A C M; van der Ley, Peter; Mooi, Frits R; Han, Wanda G H; Pinelli, Elena

    2015-01-01

    Bordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Despite high vaccination coverage, outbreaks are being increasingly reported worldwide. Possible explanations include adaptation of this pathogen, which may interfere with recognition by the innate immune system. Here, we describe innate immune recognition and responses to different B. pertussis clinical isolates. By using HEK-Blue cells transfected with different pattern recognition receptors, we found that 3 out of 19 clinical isolates failed to activate Toll-like receptor 4 (TLR4). These findings were confirmed by using the monocytic MM6 cell line. Although incubation with high concentrations of these 3 strains resulted in significant activation of the MM6 cells, it was found to occur mainly through interaction with TLR2 and not through TLR4. When using live bacteria, these 3 strains also failed to activate TLR4 on HEK-Blue cells, and activation of MM6 cells or human monocyte-derived dendritic cells was significantly lower than activation induced by the other 16 strains. Mass spectrum analysis of the lipid A moieties from these 3 strains indicated an altered structure of this molecule. Gene sequence analysis revealed mutations in genes involved in lipid A synthesis. Findings from this study indicate that B. pertussis isolates that do not activate TLR4 occur naturally and that this phenotype may give this bacterium an advantage in tempering the innate immune response and establishing infection. Knowledge on the strategies used by this pathogen in evading the host immune response is essential for the improvement of current vaccines or for the development of new ones.

  3. Altered Expression of Human Mitochondrial Branched Chain Aminotransferase in Dementia with Lewy Bodies and Vascular Dementia.

    Science.gov (United States)

    Ashby, Emma L; Kierzkowska, Marta; Hull, Jonathon; Kehoe, Patrick G; Hutson, Susan M; Conway, Myra E

    2017-01-01

    Cytosolic and mitochondrial human branched chain aminotransferase (hBCATc and hBCATm, respectively) play an integral role in brain glutamate metabolism. Regional increased levels of hBCATc in the CA1 and CA4 region of Alzheimer's disease (AD) brain together with increased levels of hBCATm in frontal and temporal cortex of AD brains, suggest a role for these proteins in glutamate excitotoxicity. Glutamate toxicity is a key pathogenic feature of several neurological disorders including epilepsy associated dementia, AD, vascular dementia (VaD) and dementia with Lewy bodies (DLB). To further understand if these increases are specific to AD, the expression profiles of hBCATc and hBCATm were examined in other forms of dementia including DLB and VaD. Similar to AD, levels of hBCATm were significantly increased in the frontal and temporal cortex of VaD cases and in frontal cortex of DLB cases compared to controls, however there were no observed differences in hBCATc between groups in these areas. Moreover, multiple forms of hBCATm were observed that were particular to the disease state relative to matched controls. Real-time PCR revealed similar expression of hBCATm mRNA in frontal and temporal cortex for all cohort comparisons, whereas hBCATc mRNA expression was significantly increased in VaD cases compared to controls. Collectively our results suggest that hBCATm protein expression is significantly increased in the brains of DLB and VaD cases, similar to those reported in AD brain. These findings indicate a more global response to altered glutamate metabolism and suggest common metabolic responses that might reflect shared neurodegenerative mechanisms across several forms of dementia.

  4. Altered heart rate control in transgenic mice carrying the KCNJ6 gene of the human chromosome 21.

    Science.gov (United States)

    Lignon, Jacques M; Bichler, Zoë; Hivert, Bruno; Gannier, François E; Cosnay, Pierre; del Rio, José A; Migliore-Samour, Danièle; Malécot, Claire O

    2008-04-22

    Congenital heart defects (CHD) are common in Down syndrome (DS, trisomy 21). Recently, cardiac sympathetic-parasympathetic imbalance has also been documented in DS adults free of any CHD. The KCNJ6 gene located on human chromosome 21 encodes for the Kir3.2/GIRK2 protein subunits of G protein-regulated K(+) (K(G)) channels and could contribute to this altered cardiac regulation. To elucidate the role of its overexpression, we used homozygous transgenic (Tg(+/+)) mice carrying copies of human KCNJ6. These mice showed human Kir3.2 mRNA expression in the heart and a 2.5-fold increased translation in the atria. Phenotypic alterations were assessed by recording electrocardiogram of urethane anesthetized mice. Chronotropic responses to direct (carbachol) and indirect (methoxamine) muscarinic stimulation were enhanced in Tg(+/+) mice with respect to wild-type (WT) mice. Alternating periods of slow and fast rhythm induced by CCPA (2-chloro-N-cyclopentyl-adenosine) were amplified in Tg(+/+) mice, resulting in a reduced negative chronotropic effect. These drugs reduced the atrial P wave amplitude and area. P wave variations induced by methoxamine and CCPA were respectively increased and reduced in the Tg(+/+) mice, while PR interval and ventricular wave showed no difference between Tg(+/+) and WT. These results indicate that Tg(+/+) mice incorporating the human KCNJ6 exhibit altered Kir3.2 expression and responses to drugs that would activate K(G) channels. Moreover, these altered expression and responses are limited to sino-atrial node and atria that normally express large amounts of K(G) channels. These data suggest that KCNJ6 could play an important role in altered cardiac regulation in DS patients.

  5. Response of a Wild Edible Plant to Human Disturbance: Harvesting Can Enhance the Subsequent Yield of Bamboo Shoots.

    Science.gov (United States)

    Katayama, Noboru; Kishida, Osamu; Sakai, Rei; Hayakashi, Shintaro; Miyoshi, Chikako; Ito, Kinya; Naniwa, Aiko; Yamaguchi, Aya; Wada, Katsunori; Kowata, Shiro; Koike, Yoshinobu; Tsubakimoto, Katsuhiro; Ohiwa, Kenichi; Sato, Hirokazu; Miyazaki, Toru; Oiwa, Shinichi; Oka, Tsubasa; Kikuchi, Shinya; Igarashi, Chikako; Chiba, Shiho; Akiyama, Yoko; Takahashi, Hiroyuki; Takagi, Kentaro

    2015-01-01

    Wild edible plants, ecological foodstuffs obtained from forest ecosystems, grow in natural fields, and their productivity depends on their response to harvesting by humans. Addressing exactly how wild edible plants respond to harvesting is critical because this knowledge will provide insights into how to obtain effective and sustainable ecosystem services from these plants. We focused on bamboo shoots of Sasa kurilensis, a popular wild edible plant in Japan. We examined the effects of harvesting on bamboo shoot productivity by conducting an experimental manipulation of bamboo shoot harvesting. Twenty experimental plots were prepared in the Teshio Experimental Forest of Hokkaido University and were assigned into two groups: a harvest treatment, in which newly emerged edible bamboo shoots were harvested (n = 10); and a control treatment, in which bamboo shoots were maintained without harvesting (n = 10). In the first year of harvesting (2013), bamboo shoot productivities were examined twice; i.e., the productivity one day after harvesting and the subsequent post-harvest productivity (2-46 days after harvesting), and we observed no difference in productivity between treatments. This means that there was no difference in original bamboo shoot productivity between treatments, and that harvesting did not influence productivity in the initial year. In contrast, in the following year (2014), the number of bamboo shoots in the harvested plots was 2.4-fold greater than in the control plots. These results indicate that over-compensatory growth occurred in the harvested plots in the year following harvesting. Whereas previous research has emphasized the negative impact of harvesting, this study provides the first experimental evidence that harvesting can enhance the productivity of a wild edible plant. This suggests that exploiting compensatory growth, which really amounts to less of a decline in productivity, may be s a key for the effective use of wild edible plants.

  6. Response of a Wild Edible Plant to Human Disturbance: Harvesting Can Enhance the Subsequent Yield of Bamboo Shoots.

    Directory of Open Access Journals (Sweden)

    Noboru Katayama

    Full Text Available Wild edible plants, ecological foodstuffs obtained from forest ecosystems, grow in natural fields, and their productivity depends on their response to harvesting by humans. Addressing exactly how wild edible plants respond to harvesting is critical because this knowledge will provide insights into how to obtain effective and sustainable ecosystem services from these plants. We focused on bamboo shoots of Sasa kurilensis, a popular wild edible plant in Japan. We examined the effects of harvesting on bamboo shoot productivity by conducting an experimental manipulation of bamboo shoot harvesting. Twenty experimental plots were prepared in the Teshio Experimental Forest of Hokkaido University and were assigned into two groups: a harvest treatment, in which newly emerged edible bamboo shoots were harvested (n = 10; and a control treatment, in which bamboo shoots were maintained without harvesting (n = 10. In the first year of harvesting (2013, bamboo shoot productivities were examined twice; i.e., the productivity one day after harvesting and the subsequent post-harvest productivity (2-46 days after harvesting, and we observed no difference in productivity between treatments. This means that there was no difference in original bamboo shoot productivity between treatments, and that harvesting did not influence productivity in the initial year. In contrast, in the following year (2014, the number of bamboo shoots in the harvested plots was 2.4-fold greater than in the control plots. These results indicate that over-compensatory growth occurred in the harvested plots in the year following harvesting. Whereas previous research has emphasized the negative impact of harvesting, this study provides the first experimental evidence that harvesting can enhance the productivity of a wild edible plant. This suggests that exploiting compensatory growth, which really amounts to less of a decline in productivity, may be s a key for the effective use of wild edible

  7. Genetic and epigenetic alterations of microRNAs and implications for human cancers and other diseases.

    Science.gov (United States)

    Tuna, Musaffe; Machado, Andreia S; Calin, George A

    2016-03-01

    MicroRNAs (miRNAs) are a well-studied group of noncoding RNAs that control gene expression by interacting mainly with messenger RNA. It is known that miRNAs and their biogenesis regulatory machineries have crucial roles in multiple cell processes; thus, alterations in these genes often lead to disease, such as cancer. Disruption of these genes can occur through epigenetic and genetic alterations, resulting in aberrant expression of miRNAs and subsequently of their target genes. This review focuses on the disruption of miRNAs and their key regulatory machineries by genetic alterations, with emphasis on mutations and epigenetic changes in cancer and other diseases.

  8. Urbanization and baseline prevalence of genital infections including Candida, Trichomonas, and human papillomavirus and of a disturbed vaginal ecology as established in the Dutch Cervical Screening Program

    NARCIS (Netherlands)

    Boon, ME; Claasen, HHV; Kok, LP

    OBJECTIVE: An overgrowth of coccoid bacilli in the absence of lactobacilli (bacterial vaginosis) is considered a sign of a "disturbed" vaginal ecologic system. The aim of this study was to establish the baseline prevalence of genital infections and of a disturbed vaginal ecologic system and their

  9. Urbanization and baseline prevalence of genital infections including Candida, Trichomonas, and human papillomavirus and of a disturbed vaginal ecology as established in the Dutch Cervical Screening Program

    NARCIS (Netherlands)

    Boon, ME; Claasen, HHV; Kok, LP

    2002-01-01

    OBJECTIVE: An overgrowth of coccoid bacilli in the absence of lactobacilli (bacterial vaginosis) is considered a sign of a "disturbed" vaginal ecologic system. The aim of this study was to establish the baseline prevalence of genital infections and of a disturbed vaginal ecologic system and their re

  10. Urbanization and baseline prevalence of genital infections including Candida, Trichomonas, and human papillomavirus and of a disturbed vaginal ecology as established in the Dutch Cervical Screening Program

    NARCIS (Netherlands)

    Boon, ME; Claasen, HHV; Kok, LP

    2002-01-01

    OBJECTIVE: An overgrowth of coccoid bacilli in the absence of lactobacilli (bacterial vaginosis) is considered a sign of a "disturbed" vaginal ecologic system. The aim of this study was to establish the baseline prevalence of genital infections and of a disturbed vaginal ecologic system and their re

  11. Human-chimpanzee differences in a FZD8 enhancer alter cell-cycle dynamics in the developing neocortex.

    Science.gov (United States)

    Boyd, J Lomax; Skove, Stephanie L; Rouanet, Jeremy P; Pilaz, Louis-Jan; Bepler, Tristan; Gordân, Raluca; Wray, Gregory A; Silver, Debra L

    2015-03-16

    The human neocortex differs from that of other great apes in several notable regards, including altered cell cycle, prolonged corticogenesis, and increased size [1-5]. Although these evolutionary changes most likely contributed to the origin of distinctively human cognitive faculties, their genetic basis remains almost entirely unknown. Highly conserved non-coding regions showing rapid sequence changes along the human lineage are candidate loci for the development and evolution of uniquely human traits. Several studies have identified human-accelerated enhancers [6-14], but none have linked an expression difference to a specific organismal trait. Here we report the discovery of a human-accelerated regulatory enhancer (HARE5) of FZD8, a receptor of the Wnt pathway implicated in brain development and size [15, 16]. Using transgenic mice, we demonstrate dramatic differences in human and chimpanzee HARE5 activity, with human HARE5 driving early and robust expression at the onset of corticogenesis. Similar to HARE5 activity, FZD8 is expressed in neural progenitors of the developing neocortex [17-19]. Chromosome conformation capture assays reveal that HARE5 physically and specifically contacts the core Fzd8 promoter in the mouse embryonic neocortex. To assess the phenotypic consequences of HARE5 activity, we generated transgenic mice in which Fzd8 expression is under control of orthologous enhancers (Pt-HARE5::Fzd8 and Hs-HARE5::Fzd8). In comparison to Pt-HARE5::Fzd8, Hs-HARE5::Fzd8 mice showed marked acceleration of neural progenitor cell cycle and increased brain size. Changes in HARE5 function unique to humans thus alter the cell-cycle dynamics of a critical population of stem cells during corticogenesis and may underlie some distinctive anatomical features of the human brain.

  12. Air toxics and epigenetic effects: ozone altered microRNAs in the sputum of human subjects

    Science.gov (United States)

    Ozone (03) is a criteria air pollutant that is associated with numerous adverse health effects, including altered respiratory immune responses. Despite its deleterious health effects, possible epigenetic mechanisms underlying 03-induced health effects remain understudied. MicroRN...

  13. Autonomic disturbances in narcolepsy.

    Science.gov (United States)

    Plazzi, Giuseppe; Moghadam, Keivan Kaveh; Maggi, Leonardo Serra; Donadio, Vincenzo; Vetrugno, Roberto; Liguori, Rocco; Zoccoli, Giovanna; Poli, Francesca; Pizza, Fabio; Pagotto, Uberto; Ferri, Raffaele

    2011-06-01

    Narcolepsy is a clinical condition characterized mainly by excessive sleepiness and cataplexy. Hypnagogic hallucinations and sleep paralysis complete the narcoleptic tetrad; disrupted night sleep, automatic behaviors and weight gain are also usual complaints. Different studies focus on autonomic changes or dysfunctions among narcoleptic patients, such as pupillary abnormalities, fainting spells, erectile dysfunction, night sweats, gastric problems, low body temperature, systemic hypotension, dry mouth, heart palpitations, headache and extremities dysthermia. Even if many studies lack sufficient standardization or their results have not been replicated, a non-secondary involvement of the autonomic nervous system in narcolepsy is strongly suggested, mainly by metabolic and cardiovascular findings. Furthermore, the recent discovery of a high risk for overweight and for metabolic syndrome in narcoleptic patients represents an important warning for clinicians in order to monitor and follow them up for their autonomic functions. We review here studies on autonomic functions and clinical disturbances in narcoleptic patients, trying to shed light on the possible contribute of alterations of the hypocretin system in autonomic pathophysiology.

  14. Alteration of Cell Cycle Mediated by Zinc in Human Bronchial Epithelial Cells In Vitro

    Science.gov (United States)

    Zinc (Zn2+), a ubiquitous ambient air contaminant, presents an oxidant challenge to the human lung and is linked to adverse human health effects. To further elucidate the adaptive and apoptotic cellular responses of human airway cells to Zn2+, we performed pilot studies to examin...

  15. Alteration of Cell Cycle Mediated by Zinc in Human Bronchial Epithelial Cells In Vitro

    Science.gov (United States)

    Zinc (Zn2+), a ubiquitous ambient air contaminant, presents an oxidant challenge to the human lung and is linked to adverse human health effects. To further elucidate the adaptive and apoptotic cellular responses of human airway cells to Zn2+, we performed pilot studies to examin...

  16. Minimal change-like glomerular alterations induced by a human plasma factor

    NARCIS (Netherlands)

    Cheung, PK; Klok, PA; Bakker, WW

    1996-01-01

    Circulating factors, including the plasma protease (100KF) described previously, have been suspected to play a role in the pathogenesis of minimal change disease (MCD) for several decades. This factor was able to induce MCD-like alterations in kidney tissue in vitro, i.e. impairment of glomerular po

  17. Identification of reference genes in human myelomonocytic cells for gene expression studies in altered gravity.

    Science.gov (United States)

    Thiel, Cora S; Hauschild, Swantje; Tauber, Svantje; Paulsen, Katrin; Raig, Christiane; Raem, Arnold; Biskup, Josefine; Gutewort, Annett; Hürlimann, Eva; Unverdorben, Felix; Buttron, Isabell; Lauber, Beatrice; Philpot, Claudia; Lier, Hartwin; Engelmann, Frank; Layer, Liliana E; Ullrich, Oliver

    2015-01-01

    Gene expression studies are indispensable for investigation and elucidation of molecular mechanisms. For the process of normalization, reference genes ("housekeeping genes") are essential to verify gene expression analysis. Thus, it is assumed that these reference genes demonstrate similar expression levels over all experimental conditions. However, common recommendations about reference genes were established during 1 g conditions and therefore their applicability in studies with altered gravity has not been demonstrated yet. The microarray technology is frequently used to generate expression profiles under defined conditions and to determine the relative difference in expression levels between two or more different states. In our study, we searched for potential reference genes with stable expression during different gravitational conditions (microgravity, normogravity, and hypergravity) which are additionally not altered in different hardware systems. We were able to identify eight genes (ALB, B4GALT6, GAPDH, HMBS, YWHAZ, ABCA5, ABCA9, and ABCC1) which demonstrated no altered gene expression levels in all tested conditions and therefore represent good candidates for the standardization of gene expression studies in altered gravity.

  18. Identification of Reference Genes in Human Myelomonocytic Cells for Gene Expression Studies in Altered Gravity

    Directory of Open Access Journals (Sweden)

    Cora S. Thiel

    2015-01-01

    Full Text Available Gene expression studies are indispensable for investigation and elucidation of molecular mechanisms. For the process of normalization, reference genes (“housekeeping genes” are essential to verify gene expression analysis. Thus, it is assumed that these reference genes demonstrate similar expression levels over all experimental conditions. However, common recommendations about reference genes were established during 1 g conditions and therefore their applicability in studies with altered gravity has not been demonstrated yet. The microarray technology is frequently used to generate expression profiles under defined conditions and to determine the relative difference in expression levels between two or more different states. In our study, we searched for potential reference genes with stable expression during different gravitational conditions (microgravity, normogravity, and hypergravity which are additionally not altered in different hardware systems. We were able to identify eight genes (ALB, B4GALT6, GAPDH, HMBS, YWHAZ, ABCA5, ABCA9, and ABCC1 which demonstrated no altered gene expression levels in all tested conditions and therefore represent good candidates for the standardization of gene expression studies in altered gravity.

  19. Spatial and temporal age-related spectral alterations in benign human breast tissue

    Science.gov (United States)

    Theophilou, Georgios; Fogarty, Simon W.; Trevisan, Júlio; Strong, Rebecca J.; Heys, Kelly A.; Patel, Imran I.; Stringfellow, Helen F.; Martin-Hirsch, Pierre L.; Martin, Francis L.

    2016-02-01

    Epidemiological evidence suggests that cancers attributable to exogenous carcinogenic agents may appear decades after initiating exposures. Environmental factors including lifestyle and/or diet have been implicated in the aetiology of breast cancer. Breast tissue undergoes continuous molecular and morphological changes from the time of thelarche to menopause and thereafter. These alterations are both cyclical and longitudinal, and can be influenced by several environmental factors including exposure to oestrogens. Research into the latent period leading to breast carcinogenesis has been mostly limited to when hyperplastic lesions are present. Investigations to identify a biomarker of commitment to disease in normal breast tissue are hindered by the molecular and histological diversity of disease-free breast tissue. Benign tissue from reduction mammoplasties provides an opportunity to study biochemical differences between women of similar ages as well as alterations with advancing age. Herein, synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy was used to examine the terminal ductal lobular epithelium (TDLU) and, intra- and inter-lobular epithelium to identify spatial and temporal changes within these areas. Principal component analysis (PCA) followed by linear discriminant analysis of mid-infrared spectra revealed unambiguous inter-individual as well as age-related differences in each histological compartment interrogated. Moreover, exploratory PCA of luminal and myoepithelial cells within the TDLU indicated the presence of specific cells, potentially stem cells. Understanding alterations within benign tissue may assist in the identification of alterations in latent pre-clinical stages of breast cancer.

  20. Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism

    DEFF Research Database (Denmark)

    Jansen, S W; Akintola, A A; Roelfsema, F;

    2015-01-01

    hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring...... may favour longevity without altering energy metabolism....

  1. Beryllium alters lipopolysaccharide-mediated intracellular phosphorylation and cytokine release in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Silva, Shannon; Ganguly, Kumkum; Fresquez, Theresa M; Gupta, Goutam; McCleskey, T Mark; Chaudhary, Anu

    2009-12-01

    Beryllium exposure in susceptible individuals leads to the development of chronic beryllium disease, a lung disorder marked by release of inflammatory cytokine and granuloma formation. We have previously reported that beryllium induces an immune response even in blood mononuclear cells from healthy individuals. In this study, we investigate the effects of beryllium on lipopolysaccharide-mediated cytokine release in blood mononuclear and dendritic cells from healthy individuals. We found that in vitro treatment of beryllium sulfate inhibits the secretion of lipopolysaccharide-mediated interleukin 10, while the release of interleukin 1beta is enhanced. In addition, not all lipopolysaccharide-mediated responses are altered, as interleukin 6 release in unaffected upon beryllium treatment. Beryllium sulfate-treated cells show altered phosphotyrosine levels upon lipopolysaccharide stimulation. Significantly, beryllium inhibits the phosphorylation of signal transducer and activator of transducer 3, induced by lipopolysaccharide. Finally, inhibitors of phosphoinositide-3 kinase mimic the effects of beryllium in inhibition of interleukin 10 release, while they have no effect on interleukin 1beta secretion. This study strongly suggests that prior exposures to beryllium could alter host immune responses to bacterial infections in healthy individuals, by altering intracellular signaling.

  2. Exposure to the three structurally different PCB congeners (PCB 118, 153, and 126) results in decreased protein expression and altered steroidogenesis in the human adrenocortical carcinoma cell line H295R.

    Science.gov (United States)

    Tremoen, Nina Hårdnes; Fowler, Paul A; Ropstad, Erik; Verhaegen, Steven; Krogenæs, Anette

    2014-01-01

    Polychlorinated biphenyls (PCB), synthetic, persistent organic pollutants (POP), are detected ubiquitously, in water, soil, air, and sediments, as well as in animals and humans. PCB are associated with range of adverse health effects, such as interference with the immune system and nervous system, reproductive abnormalities, fetotoxicity, carcinogenicity, and endocrine disruption. Our objective was to determine the effects of three structurally different PCB congeners, PCB118, PCB 126, and PCB 153, each at two concentrations, on the steroidogenic capacity and proteome of human adrenocortical carcinoma cell line cultures (H295R) . After 48 h of exposure, cell viability was monitored and estradiol, testosterone, cortisol and progesterone secretion measured to quantify steroidogenic capacity of the cells. Two-dimensional (2D) gel-based proteomics was used to screen for proteome alterations in H295R cells in response to the PCB. Exposure to PCB 118 increased estradiol and cortisol secretion, while exposure to PCB 153 elevated estradiol secretion. PCB 126 was the most potent congener, increasing estradiol, cortisol, and progesterone secretion in exposed H295R cells. Seventy-three of the 711 spots analyzed showed a significant difference in normalized spot volumes between controls (vehicle only) and at least one exposure group. Fourteen of these protein spots were identified by liquid chromatography with mass spectroscopy (LC-MS/MS). Exposure to three PCB congeners with different chemical structure perturbed steroidogenesis and protein expression in the H295R in vitro model. This study represents an initial analysis of the effects on proteins and hormones in the H295R cell model, and additional studies are required in order to obtain a more complete understanding of the pathways disturbed by PCB congeners in H295R cells. Overall, alterations in protein regulation and steroid hormone synthesis suggest that exposure to PCB disturbs several cellular processes, including

  3. Isotope hydrology and baseflow geochemistry in natural and human-altered watersheds in the Inland Pacific Northwest, USA.

    Science.gov (United States)

    Sánchez-Murillo, Ricardo; Brooks, Erin S; Elliot, William J; Boll, Jan

    2015-01-01

    This study presents a stable isotope hydrology and geochemical analysis in the inland Pacific Northwest (PNW) of the USA. Isotope ratios were used to estimate mean transit times (MTTs) in natural and human-altered watersheds using the FLOWPC program. Isotope ratios in precipitation resulted in a regional meteoric water line of δ(2)H = 7.42·δ(18)O + 0.88 (n = 316; r(2) = 0.97). Isotope compositions exhibited a strong temperature-dependent seasonality. Despite this seasonal variation, the stream δ(18)O variation was small. A significant regression (τ = 0.11D(-1.09); r(2) = 0.83) between baseflow MTTs and the damping ratio was found. Baseflow MTTs ranged from 0.4 to 0.6 years (human-altered), 0.7 to 1.7 years (mining-altered), and 0.7 to 3.2 years (forested). Greater MTTs were represented by more homogenous aqueous chemistry whereas smaller MTTs resulted in more dynamic compositions. The isotope and geochemical data presented provide a baseline for future hydrological modelling in the inland PNW.

  4. Human reproductive system disturbances and pesticide exposure in Brazil Distúrbios do sistema reprodutivo humano e exposição a pesticidas no Brasil

    Directory of Open Access Journals (Sweden)

    Sergio Koifman

    2002-04-01

    Full Text Available The observation of reproductive disturbances in humans and in the wildlife has been reported in the last decade in different countries. Exposure to different chemicals possibly acting in the endocrine system or endocrine disruptors, including pesticides, has been a hypothesis raised to explain the observed changes. This paper aimed to present results of an epidemiological ecologic study carried out to explore population data on pesticides exposure in selected Brazilian states in the eighties and human reproductive outcomes in the nineties. Pearson correlation coefficients were ascertained between available data pesticides sales in eleven states in Brazil in 1985 and selected further reproductive outcomes or their surrogates. Moderate to high correlations were observed to infertility, testis, breast, prostate and ovarian cancer mortality. Despite the restrains of ecologic studies to establish cause-effect relationships, the observed results are in agreement with evidence supporting a possible association between pesticides exposure and the analyzed reproductive outcomes.A observação de distúrbios reprodutivos em seres humanos e na vida animal tem sido relatada em diferentes países na última década, sendo apontada como possível explicação para tal fenômeno, a exposição a diversas substâncias químicas com possível interferência no sistema endócrino, incluindo pesticidas. Este trabalho apresenta os resultados de um estudo epidemiológico, com delineamento ecológico explorando dados de exposição a pesticidas durante os anos oitenta, em estados brasileiros selecionados e distúrbios reprodutivos observados nos anos noventa. Foram obtidos coeficientes de correlação de Pearson entre o volume de vendas de pesticidas em onze estados brasileiros em 1985 e indicadores diretos ou substitutos da ocorrência de distúrbios reprodutivos nas mesmas localidades. Coeficientes de correlação moderados e elevados foram observados para a

  5. Mitochondrial structure alteration in human prostate cancer cells upon initial interaction with a chemopreventive agent phenethyl isothiocyanate.

    Science.gov (United States)

    Xue, Chengsen; Pasolli, Hilda A; Piscopo, Irene; Gros, Daniel J; Liu, Christina; Chen, Yamei; Chiao, Jen Wei

    2014-03-31

    Phenethyl isothiocyanate (PEITC), present naturally in cruciferous vegetables, is a chemopreventive agent. It blocks initiation and post-initiation progression of carcinogenesis. Mechanism study in human prostate cancer cells revealed that PEITC is a dual inhibitor of aberrant DNA hypermethylation and histone deacetylases, reactivating silenced genes and regulating the androgen-mediated growth of tumor cells. The identity of the cellular organelle that initially interacts with PEITC has not been fully described. Human prostate cancer LNCaP cells were exposed to PEITC and the effects on cellular fine structure examined by transmission electron microscopic studies. Alteration of mitochondrial membrane potential and cytochrome c release were evaluated as early events of apoptosis, and the TUNEL method for quantifying apoptotic cells. Mitochondria were isolated for determining their protein expression. Ultrastructural analyses have revealed condensed mitochondria and a perturbed mitochondrial cristae structure, which assumed a rounded and dilated shape within 4-hours of PEITC contact, and became more pronounced with longer PEITC exposure. They presented as the most prominent intracellular alterations in the early hours. Mitochondria structure alterations were demonstrated, for the first time, with the isothiocyanates. An increase in the number of smooth endoplasmic reticulum and vacuoles were also noted that is consistent with the presence of autophagy. Early events of apoptosis were detected, with cytochrome c released along with the appearance of mitochondrial alteration. Mitochondrial membrane potential was disrupted within 18 hours of PEITC exposure, preceding the appearance of apoptotic cells with DNA strand breaks. In parallel, the expression of the mitochondrial class III ß-tubulin in the outer membrane, which associates with the permeability transition pore, was significantly reduced as examined with isolated mitochondria. Mitochondria may represent the

  6. Shielding of the Geomagnetic Field Alters Actin Assembly and Inhibits Cell Motility in Human Neuroblastoma Cells

    OpenAIRE

    Wei-Chuan Mo; Zi-Jian Zhang; Dong-Liang Wang; Ying Liu; Bartlett, Perry F.; Rong-Qiao He

    2016-01-01

    Accumulating evidence has shown that absence of the geomagnetic field (GMF), the so-called hypomagnetic field (HMF) environment, alters the biological functions in seemingly non-magnetosensitive cells and organisms, which indicates that the GMF could be sensed by non-iron-rich and non-photo-sensing cells. The underlying mechanisms of the HMF effects on those cells are closely related to their GMF sensation but remain poorly understood so far. Previously, we found that the HMF represses expres...

  7. Alterations of consciousness and mystical-type experiences after acute LSD in humans.

    Science.gov (United States)

    Liechti, Matthias E; Dolder, Patrick C; Schmid, Yasmin

    2017-05-01

    Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking. We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg. On the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg. Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.

  8. Human giant congenital melanocytic nevus exhibits potential proteomic alterations leading to melanotumorigenesis

    Directory of Open Access Journals (Sweden)

    Kim Hyoung Kyu

    2012-08-01

    Full Text Available Abstract Background A giant congenital melanocytic nevus (GCMN is a malformation of the pigment cells. It is a distress to the patients for two reasons: one is disfigurement, and the other is the possibility of malignant changes. However, the underlying mechanisms of the development of GCMN and melanotumorigenesis in GCMN are unknown. Hence, the aim of this study was to identify the proteomic alterations and associated functional pathways in GCMN. Results Proteomic differences between GCMN (n = 3 and normal skin samples (n = 3 were analyzed by one-dimensional-liquid chromatography-tandem mass spectrometry Relative levels of the selected proteins were validated using western blot analysis. The biological processes associated with the abundance modified proteins were analyzed using bioinformatic tools. Among the 46 abundance modified proteins, expression of 4 proteins was significantly downregulated and expression of 42 proteins was significantly upregulated in GCMN compared to normal skin samples (p  Conclusion These findings suggest that GCMN exhibits potential proteomic alterations, which may play a role in melanotumorigenesis, and the significant alteration of 14-3-3 family proteins could be a key regulator of the biological pathway remodeling in GCMN.

  9. The resonant component of human physiological hand tremor is altered by slow voluntary movements.

    Science.gov (United States)

    Lakie, Martin; Vernooij, Carlijn A; Osborne, Timothy M; Reynolds, Raymond F

    2012-05-15

    Limb resonance imparts a characteristic spectrum to hand tremor. Movement will alter the resonance. We have examined the consequences of this change. Rectified forearm extensor muscle EMG and physiological hand tremor were recorded. In postural conditions the EMG spectrum is relatively flat whereas the acceleration spectrum is sharply peaked. Consequently, the gain between EMG and acceleration is maximal at the frequency where the tremor is largest (∼8 Hz). The shape of the gain curve implies mechanical resonance. Substantial alterations in posture do not significantly change the characteristics of the tremor or the shape or size of the gain curve. By contrast, slow or moderately paced voluntary wrist flexion–extension movements dramatically increase the hand tremor size and lower its peak frequency. These changes in size and frequency of the tremor cannot be attributed to changes in the EMG. Instead they reflect a very large change in the size and shape of the gain curve relating EMG to acceleration. The gain becomes larger and the peak moves to a lower frequency (∼6 Hz). We suggest that a movement-related (thixotropic) alteration in resonant properties of the wrist provides a simple explanation for these changes. The mechanism is illustrated by a model. Our new findings confirm that resonance plays a major role in wrist tremor. We also demonstrate that muscles operate very differently under postural and dynamic conditions. The different coupling between EMG and movement in posture and when moving must pose a considerable challenge for neural predictive control of skeletal muscles.

  10. Sleep disturbances after non-cardiac surgery

    DEFF Research Database (Denmark)

    Rosenberg, Jacob

    2001-01-01

    After major non-cardiac surgery sleep pattern is usually disturbed with initial suppression of rapid eye movement sleep with a subsequent rebound during the first post-operative week. Deep sleep is also suppressed for several days after the operation and subjective sleep quality is impaired....... The sleep disturbances seem to be related to the magnitude of trauma and thereby to the surgical stress response and/or post-operative opioid administration. Post-operative sleep disturbances may contribute to the development of early post-operative fatigue, episodic hypoxaemia, haemodynamic instability...... and altered mental status, all with a potential negative effect on post-operative outcome. Minimizing surgical trauma and avoiding or minimizing use of opioids for pain relief may prevent or reduce post-operative sleep disturbances. Post-operative sleep pattern represents an important research field, since...

  11. Bisphenol A and its analogs induce morphological and biochemical alterations in human peripheral blood mononuclear cells (in vitro study).

    Science.gov (United States)

    Michałowicz, Jaromir; Mokra, Katarzyna; Bąk, Agata

    2015-10-01

    Few studies have addressed the cellular effects of bisphenol S (BPS) and bisphenol AF (BPAF) on cells, and no study has been conducted to analyze the mechanism of action of bisphenols in blood cells. In this study, the effect of bisphenol A (BPA), bisphenol F (BPF), BPS and BPAF on human peripheral blood mononuclear cells (PBMCs) was analyzed. It was shown that BPA, BPF and BPAF in particular, decreased cell viability, which was associated with depletion of intracellular ATP level and alterations in PBMCs size and granulation. Bisphenols enhanced ROS (including OH˙) formation, which led to damage to lipids and proteins in PBMCs. The most significant alterations in ROS level were induced by BPF, and particularly BPAF. Moreover, it was shown that BPAF most strongly provoked lipid peroxidation, while BPA and BPS caused the greatest damage to proteins. It may be concluded that BPA and its analogs were capable of inducing oxidative stress and damage in PBMCs in the concentrations ranging from 0.06 to 0.5 μM (0.02-0.1 μg/ml), which may be present in human blood as a result of environmental exposure. Although, most of bisphenols studied decreased cell viability, size and ATP level at higher concentrations, BPAF exhibited its cytotoxic potential at low concentrations ranging from 0.3 to 3 μM (0.1-1.0 μg/ml) that may correspond to concentrations in humans following occupational exposure.

  12. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain

    DEFF Research Database (Denmark)

    Olesen, R H; Hyde, T M; Kleinman, J E

    2016-01-01

    participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African......The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc...

  13. Forest loss increases insect herbivory levels in human-altered landscapes

    Science.gov (United States)

    Dodonov, Pavel; Morante-Filho, José Carlos; Mariano-Neto, Eduardo; Cazetta, Eliana; Andrade, Edyla Ribeiro de; Rocha-Santos, Larissa; Inforzato, Igor; Gomes, Francisco Sanches; Faria, Deborah

    2016-11-01

    Insect herbivory has been observed to be affected by habitat loss and fragmentation, although the mechanisms by which these anthropogenic disturbances affect this process are not well understood. To aid in clarifying this issue, we assessed the relation between forest cover and leaf damage caused by herbivorous insects on a representative tropical forest understory plant family, the Rubiaceae. We measured leaf area loss of Rubiaceae plants in 20 forest sites located in the Brazilian Atlantic forest, and also tested whether variation in forest cover, abundance of insectivorous birds (predators) and of Rubiaceae plants (resources) could explain the observed variation in leaf damage. Herbivory levels varied between 2.6 and 12.5 percent leaf area lost and increased with decreasing forest cover, whereas the other explanatory variables did not provide additional explanatory power. Therefore, forest loss appears to be the main driver of changes in local herbivory, and ecological processes such as top-down and bottom-up control may not account for the deforestation-related increase in herbivory levels. Other mechanisms, for example leaf quality and/or the influence of the adjoining land uses, have to be explored in future studies.

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

    Directory of Open Access Journals (Sweden)

    Saura C. Sahu

    2016-01-01

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

  15. Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity

    National Research Council Canada - National Science Library

    Dolinska, Monika B; Kovaleva, Elena; Backlund, Peter; Wingfield, Paul T; Brooks, Brian P; Sergeev, Yuri V

    2014-01-01

    .... The intra-melanosomal domain of human tyrosinase (residues 19-469) and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced in T. ni larvae...

  16. Albinism-Causing Mutations in Recombinant Human Tyrosinase Alter Intrinsic Enzymatic Activity: e84494

    National Research Council Canada - National Science Library

    Monika B Dolinska; Elena Kovaleva; Peter Backlund; Paul T Wingfield; Brian P Brooks; Yuri V Sergeev

    2014-01-01

    .... Methodology/Principal Findings The intra-melanosomal domain of human tyrosinase (residues 19-469) and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced...

  17. Restoration of sand dunes along human-altered coasts: a scheme for Miramar beach, Goa

    Digital Repository Service at National Institute of Oceanography (India)

    Mascarenhas, A.

    This paper examines the state of sand dunes of a developed coast by taking the tourist beach of Miramar (Goa), India as an example. Human actions are responsible for the degradation and elimination of these geomorphic features. The associated...

  18. Detecting alterations of glucose and lipid components in human serum by near-infrared Raman spectroscopy

    OpenAIRE

    Borges,Rita de Cássia Fernandes; NAVARRO, Ricardo Scarparo; Giana,Hector Enrique; Tavares,Fernanda Grubisich; Fernandes,Adriana Barrinha; Silveira Junior, Landulfo

    2015-01-01

    Introduction Raman spectroscopy may become a tool for the analysis of glucose and triglycerides in human serum in real time. This study aimed to detect spectral differences in lipid and glucose components of human serum, thus evaluating the feasibility of Raman spectroscopy for diagnostic purposes. Methods A total of 44 samples of blood serum were collected from volunteers and submitted for clinical blood biochemical analysis. The concentrations of glucose, cholesterol, triglycerides, and low...

  19. Idiosyncratic responses of Amazonian birds to primary forest disturbance.

    Science.gov (United States)

    Moura, Nárgila G; Lees, Alexander C; Aleixo, Alexandre; Barlow, Jos; Berenguer, Erika; Ferreira, Joice; Mac Nally, Ralph; Thomson, James R; Gardner, Toby A

    2016-03-01

    As humans continue to alter tropical landscapes across the world, it is important to understand what environmental factors help determine the persistence of biodiversity in modified ecosystems. Studies on well-known taxonomic groups can offer critical insights as to the fate of biodiversity in these modified systems. Here we investigated species-specific responses of 44 forest-associated bird species with different behavioural traits to forest disturbance in 171 transects distributed across 31 landscapes in two regions of the eastern Brazilian Amazon. We investigated patterns of species occurrence in primary forests varyingly disturbed by selective-logging and fire and examined the relative importance of local, landscape and historical environmental variables in determining species occurrences. Within undisturbed and disturbed primary forest transects, we found that distance to forest edge and the biomass of large trees were the most important predictors driving the occurrence of individual species. However, we also found considerable variation in species responses to different environmental variables as well as inter-regional variation in the responses of the same species to the same environmental variables. We advocate the utility of using species-level analyses to complement community-wide responses in order to uncover highly variable and species-specific responses to environmental change that remain so poorly understood.

  20. The renal metallothionein expression profile is altered in human lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Penkowa, Milena; Andersen, Claus Bøgelund

    2008-01-01

    INTRODUCTION: Metallothionein (MT) isoforms I + II are polypeptides with potent antioxidative and anti-inflammatory properties. In healthy kidneys, MT-I+II have been described as intracellular proteins of proximal tubular cells. The aim of the present study was to investigate whether the renal MT...... alterations in renal MT-I+II expression. Our data indicate that important prognostic information can be deduced from the renal MT-I+II expression profile in systemic lupus erythematosus patients with nephritis.......-I+II expression profile is altered during lupus nephritis. METHODS: Immunohistochemistry was performed on renal biopsies from 37 patients with lupus nephritis. Four specimens of healthy renal tissue served as controls. Clinicopathological correlation studies and renal survival analyses were performed by means...... of standard statistical methods. RESULTS: Proximal tubules displaying epithelial cell MT-I+II depletion in combination with luminal MT-I+II expression were observed in 31 out of 37 of the lupus nephritis specimens, but not in any of the control sections (P = 0.006). The tubular MT score, defined as the median...

  1. The standardized psychometric assessment of altered states of consciousness (ASCs) in humans.

    Science.gov (United States)

    Dittrich, A

    1998-07-01

    The APZ questionnaire was developed in order to explore hypotheses on ASCs. First -- in a series of 11 experiments using different induction methods on N = 393 healthy subjects -- the hypothesis was tested that ASCs have major dimensions in common irrespective of the mode of their induction. In the International Study on Altered States of Consciousness (ISASC) the external validity of the experimental results was assessed. The ISASC was carried out on a total of N = 1133 subjects in six countries. The main results of the experimental studies were corroborated in the field studies. The results can be summarized as follows: the common denominator of ASCs is described by three oblique dimensions, designated as "Oceanic Boundlessness (OSE)", "Dread of Ego Dissolution (AIA)" and "Visionary Restructuralization (VUS)". The reliability and validity of the scales are satisfactory. Tested versions of the APZ scales are available in English (UK, USA), German, Italian and Portuguese. Psychometrically as yet untested versions exist in Dutch, Finnish, French, Greek, Spanish and Russian. The APZ questionnaire has become the international standard for the assessment of ASCs, thus helping to integrate research. A psychometrically improved version exists in German (OAV questionnaire). The BETA questionnaire, which measures the dimensions "Vigilance Reduction (VIR)" and "Auditive Alteration (AVE)" is also available in German. These dimensions are most likely etiology-dependent.

  2. Anal cancer in Chinese: human papillomavirus infection and altered expression of p53

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    AIM To detect the presence of HPV DNA and study the alteration of p53 expression in anal cancers in Chinese.METHODS HPV DNA was amplified by PCR. The amplified HPV DNA was classified by DBH. HPV antigen and p53 expression were respectively detected by immunohistochemistry.RESULTS HPV DNA was amplified only in one case of squamous cell carcinoma of the 72 Chinese anal cancers and further classified as HPV type 16. Others were all HPV negative. HPV antigen and p53 expression were also detected in this case. Positive stainings with anti-p53 antibody were seen in 61.2% anal cancers. There were no statistically significant differences between anal squamous cell carcinomas and adenocarcinomas and between anal adenocarcinomas and rectal adenocarcinomas. p53 protein expression was observed in the basal cells of squamous epithelium of condyloma acuminatum and morphologically normal squamous epithelium in 2 cases invaded by anal adenocarcinoma.CONCLUSION HPV infection was not associated with these cases of anal cancer. p53 alteration was a common event. Positive p53 immunostaining can not be regarded as a marker for differentiating benign from malignant lesions.

  3. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging: A Mini-Review.

    Science.gov (United States)

    Quan, Taihao; Fisher, Gary J

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This mini-review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment, which contributes to decline of human skin function.

  4. Montelukast prevents microparticle-induced inflammatory and functional alterations in human bronchial smooth muscle cells.

    Science.gov (United States)

    Fogli, Stefano; Stefanelli, Fabio; Neri, Tommaso; Bardelli, Claudio; Amoruso, Angela; Brunelleschi, Sandra; Celi, Alessandro; Breschi, Maria Cristina

    2013-10-01

    Microparticles (MPs) are membrane fragments that may play a role in the pathogenesis of chronic respiratory diseases. We aimed to investigate whether human monocytes/macrophage-derived MPs could induce a pro-inflammatory phenotype in human bronchial smooth muscle cells (BSMC) and the effect of montelukast in this setting. Experimental methods included isolation of human monocytes/macrophages and generation of monocyte-derived MPs, RT-PCR analysis of gene expression, immunoenzymatic determination of pro-inflammatory factor release, bioluminescent assay of intracellular cAMP levels and electromobility shift assay analysis of NF-κB nuclear translocation. Stimulation of human BSMC with monocyte-derived MPs induced a pro-inflammatory switch in human BSMC by inducing gene expression (COX-2 and IL-8), protein release in the supernatant (PGE2 and IL-8), and heterologous β2-adrenoceptor desensitization. The latter effect was most likely related to autocrine PGE2 since pre-treatment with COX inhibitors restored the ability of salbutamol to induce cAMP synthesis in desensitized cells. Challenge with MPs induced nuclear translocation of NF-κB and selective NF-κB inhibition decreased MP-induced cytokine release in the supernatant. Montelukast treatment prevented IL-8 release and heterologous β2-adrenoceptor desensitization in human BSMC exposed to monocyte-derived MPs by blocking NF-κB nuclear translocation. These findings provide evidence on the role of human monocyte-derived MPs in the airway smooth muscle phenotype switch as a novel potential mechanism in the progression of chronic respiratory diseases and on the protective effects by montelukast in this setting.

  5. Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Mathieu Barbier

    Full Text Available Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM in humans, suggesting that platelets play a role in the pathogenesis of this syndrome. In vitro co-cultures have shown that platelets can act as a bridge between Plasmodium falciparum-infected red blood cells (pRBC and human brain microvascular endothelial cells (HBEC and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGFβ-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM.

  6. Micro RNAs and DNA methylation are regulatory players in human cells with altered X chromosome to autosome balance

    Science.gov (United States)

    Rajpathak, Shriram N.; Deobagkar, Deepti D.

    2017-01-01

    The gene balance hypothesis predicts that an imbalance in the dosage sensitive genes affects the cascade of gene networks that may influence the fitness of individuals. The phenotypes associated with chromosomal aneuploidies demonstrate the importance of gene dosage balance. We have employed untransformed human fibroblast cells with different number of X chromosomes to assess the expression of miRNAs and autosomal genes in addition to the DNA methylation status. High throughput NGS analysis using illumina Next seq500 has detected several autosomal as well as X linked miRNAs as differentially expressed in X monosomy and trisomy cells. Two of these miRNAs (hsa-miR-125a-5p and 335-5p) are likely to be involved in regulation of the autosomal gene expression. Additionally, our data demonstrates altered expression and DNA methylation signatures of autosomal genes in X monosomy and trisomy cells. In addition to miRNAs, expression of DNMT1 which is an important epigenetic player involved in many processes including cancer, is seen to be altered. Overall, present study provides a proof for regulatory roles of micro RNAs and DNA methylation in human X aneuploidy cells opening up possible new ways for designing therapeutic strategies. PMID:28233878

  7. Altered white matter in early visual pathways of humans with amblyopia.

    Science.gov (United States)

    Allen, Brian; Spiegel, Daniel P; Thompson, Benjamin; Pestilli, Franco; Rokers, Bas

    2015-09-01

    Amblyopia is a visual disorder caused by poorly coordinated binocular input during development. Little is known about the impact of amblyopia on the white matter within the visual system. We studied the properties of six major visual white-matter pathways in a group of adults with amblyopia (n=10) and matched controls (n=10) using diffusion weighted imaging (DWI) and fiber tractography. While we did not find significant differences in diffusion properties in cortico-cortical pathways, patients with amblyopia exhibited increased mean diffusivity in thalamo-cortical visual pathways. These findings suggest that amblyopia may systematically alter the white matter properties of early visual pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. DNA methylation is altered in B and NK lymphocytes in obese and type 2 diabetic human

    DEFF Research Database (Denmark)

    Simar, David; Versteyhe, Soetkin; Donkin, Ida

    2014-01-01

    Objective Obesity is associated with low-grade inflammation and the infiltration of immune cells in insulin-sensitive tissues, leading to metabolic impairment. Epigenetic mechanisms control immune cell lineage determination, function and migration and are implicated in obesity and type 2 diabetes...... (T2D). The aim of this study was to determine the global DNA methylation profile of immune cells in obese and T2D individuals in a cell type-specific manner. Material and methods Fourteen obese subjects and 11 age-matched lean subjects, as well as 12 T2D obese subjects and 7 age-matched lean subjects.......001). Results Global DNA methylation in peripheral blood mononuclear cells, monocytes, lymphocytes or T cells was not altered in obese or T2D subjects. However, analysis of blood fractions from lean, obese, and T2D subjects showed increased methylation levels in B cells from obese and T2D subjects...

  9. Arsenic alters ATP-dependent Ca²+ signaling in human airway epithelial cell wound response.

    Science.gov (United States)

    Sherwood, Cara L; Lantz, R Clark; Burgess, Jefferey L; Boitano, Scott

    2011-05-01

    Arsenic is a natural metalloid toxicant that is associated with occupational inhalation injury and contaminates drinking water worldwide. Both inhalation of arsenic and consumption of arsenic-tainted water are correlated with malignant and nonmalignant lung diseases. Despite strong links between arsenic and respiratory illness, underlying cell responses to arsenic remain unclear. We hypothesized that arsenic may elicit some of its detrimental effects on the airway through limitation of innate immune function and, specifically, through alteration of paracrine ATP (purinergic) Ca²+ signaling in the airway epithelium. We examined the effects of acute (24 h) exposure with environmentally relevant levels of arsenic (i.e., salt and water transport, bactericide production, and wound repair). Arsenic-induced compromise of such airway defense mechanisms may be an underlying contributor to chronic lung disease.

  10. Giant axonal neuropathy alters the structure of keratin intermediate filaments in human hair.

    Science.gov (United States)

    Soomro, Asfia; Alsop, Richard J; Negishi, Atsuko; Kreplak, Laurent; Fudge, Douglas; Kuczmarski, Edward R; Goldman, Robert D; Rheinstädter, Maikel C

    2017-04-01

    Giant axonal neuropathy (GAN) follows an autosomal recessive genetic inheritance and impedes the peripheral and central nervous system due to axonal swellings that are packed with neurofilaments. The patients display a number of phenotypes, including hypotonia, muscle weakness, decreased reflexes, ataxia, seizures, intellectual disability, pale skin and often curled hair. We used X-ray diffraction and tensile testing to determine potential changes to the structure of keratin intermediate filaments (IFs) in the hair of patients with GAN. A statistically significant decrease in the 47 and the 27 Å diffraction signals were observed. Tensile tests determined that the hair was slightly stiffer, stronger and more extensible in GAN patients. These results suggest that the structure of keratin IFs in hair is altered in GAN, and the findings are compatible with an increased positional disorder of the keratin tetramers within the hair fibres. © 2017 The Author(s).

  11. Communication with Disturbance Constraints

    CERN Document Server

    Bandemer, Bernd

    2011-01-01

    The problem of communication with disturbance constraints is introduced. The rate-disturbance region is established for the single constraint case. The optimal encoding scheme turns out to be the same as the Han-Kobayashi scheme for the two user-pair interference channel. For communication with two disturbance constraints, a coding scheme and a corresponding inner bound for the deterministic case are presented. The results suggest a natural way to obtain a new inner bound on the capacity region of the interference channel with more than two user pairs.

  12. Serum vitamin D levels are not altered after controlled diesel exhaust exposures in healthy human subjects

    Science.gov (United States)

    Past research has suggested that exposure to urban air pollution may be associated with vitamin D deficiency in human populations. Vitamin D is widely known for its importance in bone growth/remodeling, muscle metabolism, and its ability to promote calcium absorption in the gut; ...

  13. Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis

    DEFF Research Database (Denmark)

    Jafari Kermani, Abbas; Qanie, Diyako; Andersen, Thomas L

    2017-01-01

    Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells...

  14. Cyclic strain alters the expression and release of angiogenic factors by human tendon cells.

    Science.gov (United States)

    Mousavizadeh, Rouhollah; Khosravi, Shahram; Behzad, Hayedeh; McCormack, Robert G; Duronio, Vincent; Scott, Alex

    2014-01-01

    Angiogenesis is associated with the tissue changes underlying chronic overuse tendinopathy. We hypothesized that repetitive, cyclic loading of human tendon cells would lead to increased expression and activity of angiogenic factors. We subjected isolated human tendon cells to overuse tensile loading using an in vitro model (1 Hz, 10% equibiaxial strain). We found that mechanically stimulated human tendon cells released factors that promoted in vitro proliferation and tube formation by human umbilical vein endothelial cells (HUVEC). In response to cyclic strain, there was a transient increase in the expression of several angiogenic genes including ANGPTL4, FGF-2, COX-2, SPHK1, TGF-alpha, VEGF-A and VEGF-C, with no change in anti-angiogenic genes (BAI1, SERPINF1, THBS1 and 2, TIMP1-3). Cyclic strain also resulted in the extracellular release of ANGPTL4 protein by tendon cells. Our study is the first report demonstrating the induction of ANGPTL4 mRNA and release of ANGPTL4 protein in response to cyclic strain. Tenocytes may contribute to the upregulation of angiogenesis during the development of overuse tendinopathy.

  15. Altered gene expression of Staphylococcus aureus upon interaction with human endothelial cells

    NARCIS (Netherlands)

    Vriesema, A.J.M.; Beekhuizen, H.; Hamdi, M.; Soufan, A.; Lammers, A.; Willekens, B.; Bakker, O.; Veltrop, M.H.A.M.; Gevel, van de J.S.; Dankert, J.; Zaat, S.A.J.

    2000-01-01

    Staphylococcus aureus is isolated from a substantial number of patients with infective endocarditis who are not known to have predisposing heart abnormalities. It has been suggested that the infection is initiated by the direct binding of S. aureus to human vascular endothelium. To determine the mut

  16. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    Science.gov (United States)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-03-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

  17. Cellular and molecular alterations in human epithelial cells transformed by high let radiation

    Science.gov (United States)

    Hei, T. K.; Piao, C. Q.; Sutter, T.; Willey, J. C.; Suzuki, K.

    An understanding of the radiobiological effects of high LET radiation is essential for human risk estimation and radiation protection. In the present study, we show that a single, 30 cGy dose of 150 keV/mum ^4He ions can malignantly transform human papillomavirus immortalized human bronchial epithelial [BEP2D] cells. Transformed cells produce progressively growing tumors in nude mice. The transformation frequency by the single dose of alpha particles is estimated to be approximately 4 x 10^-7. Based on the average cross-sectional area of BEP2D cells, it can be calculated that a mean traversal of 1.4 particles per cell is sufficient to induce tumorigenic conversion of these cells 3 to 4 months post-irradiation. Tumorigenic BEP2D cells overexpress mutated p53 tumor suppressor oncoproteins in addition to the cell cycle control gene cyclin D1 and D2. This model provides an opportunity to study the cellular and molecular changes at the various stages in radiation carcinogenesis involving human cells.

  18. Wolbachia infection does not alter attraction of the mosquito Aedes (Stegomyia) aegypti to human odours

    NARCIS (Netherlands)

    Turley, A.P.; Smallegange, R.C.; Takken, W.; Zalucki, M.P.; O'Neill, S.L.; McGraw, E.A.

    2014-01-01

    The insect endosymbiont Wolbachia pipientis (Rickettsiales: Rickettsiaceae) is undergoing field trials around the world to determine if it can reduce transmission of dengue virus from the mosquito Stegomyia aegypti to humans. Two different Wolbachia strains have been released to date. The primary

  19. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    Science.gov (United States)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-01-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development. PMID:28266608

  20. Wolbachia infection does not alter attraction of the mosquito Aedes (Stegomyia) aegypti to human odours

    NARCIS (Netherlands)

    Turley, A.P.; Smallegange, R.C.; Takken, W.; Zalucki, M.P.; O'Neill, S.L.; McGraw, E.A.

    2014-01-01

    The insect endosymbiont Wolbachia pipientis (Rickettsiales: Rickettsiaceae) is undergoing field trials around the world to determine if it can reduce transmission of dengue virus from the mosquito Stegomyia aegypti to humans. Two different Wolbachia strains have been released to date. The primary ef

  1. Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice.

    Science.gov (United States)

    Fatemi, S H; Emamian, E S; Sidwell, R W; Kist, D A; Stary, J M; Earle, J A; Thuras, P

    2002-01-01

    Epidemiological reports describe a strong association between prenatal human influenza viral infection and later development of schizophrenia. Postmodern human brain studies, however, indicate a lack of gliosis in schizophrenic brains presumably secondary to absence of glial cells during the second trimester viral infection in utero. We hypothesized that human influenza infection in day 9 pregnant mice would alter the expression of glial fibrillary acidic protein (GFAP, an important marker of gliosis, neuron migration, and reactive injury) in developing brains of postnatal days 0, 14 and 35 mice. Determination of cellular GFAP immunoreactivity (IR) expressed as cell density in cortex and hippocampus of control and experimental brains showed increases in GFAP-positive density in exposed cortical (P = 0.03 day 14 vs control) and hippocampal cells (P = 0.035 day 14, P = 0.034 day 35). Similarly, ependymal cell layer GFAP-IR cell counts showed increases with increasing brain age from day 0, to days 14 and 35 in infected groups (P = 0.037, day 14) vs controls. The GFAP-positive cells in prenatally exposed brains showed 'hypertrophy' and more stellate morphology. These results implicate a significant role of prenatal human influenza viral infection on subsequent gliosis, which persists throughout brain development in mice from birth to adolescence.

  2. Fatty Acid Esters of Phloridzin Induce Apoptosis of Human Liver Cancer Cells through Altered Gene Expression

    Science.gov (United States)

    Nair, Sandhya V. G.; Ziaullah; Rupasinghe, H. P. Vasantha

    2014-01-01

    Phloridzin (phlorizin or phloretin 2′-O-glucoside) is known for blocking intestinal glucose absorption. We have investigated the anticarcinogenic effect of phloridzin and its novel derivatives using human cancer cell lines. We have synthesised novel acylated derivatives of phloridzin with six different long chain fatty acids by regioselective enzymatic acylation using Candida Antarctica lipase B. The antiproliferative effects of the new compounds were investigated in comparison with the parent compounds, phloridzin, aglycone phloretin, the six free fatty acids and chemotherapeutic drugs (sorafenib, doxorubicin and daunorubicin) using human hepatocellular carcinoma HepG2 cells, human breast adenocarcinoma MDA-MB-231 cells and acute monocytic leukemia THP-1 cells along with normal human and rat hepatocytes. The fatty acid esters of phloridzin inhibited significantly the growth of the two carcinoma and leukemia cells while similar treatment doses were not toxic to normal human or rat hepatocytes. The antiproliferative potency of fatty esters of phloridzin was comparable to the potency of the chemotherapeutic drugs. The fatty acid esters of phloridzin inhibited DNA topoisomerases IIα activity that might induce G0/G1 phase arrest, induced apoptosis via activation of caspase-3, and decreased ATP level and mitochondrial membrane potential in HepG2 cells. Based on the high selectivity on cancer cells, decosahexaenoic acid (DHA) ester of phloridzin was selected for gene expression analysis using RT2PCR human cancer drug target array. Antiproliferative effect of DHA ester of phloridzin could be related to the down regulation of anti-apoptotic gene (BCL2), growth factor receptors (EBFR family, IGF1R/IGF2, PDGFR) and its downstream signalling partners (PI3k/AKT/mTOR, Ras/Raf/MAPK), cell cycle machinery (CDKs, TERT, TOP2A, TOP2B) as well as epigenetics regulators (HDACs). These results suggest that fatty esters of phloridzin have potential chemotherapeutic effects mediated

  3. Fatty acid esters of phloridzin induce apoptosis of human liver cancer cells through altered gene expression.

    Directory of Open Access Journals (Sweden)

    Sandhya V G Nair

    Full Text Available Phloridzin (phlorizin or phloretin 2'-O-glucoside is known for blocking intestinal glucose absorption. We have investigated the anticarcinogenic effect of phloridzin and its novel derivatives using human cancer cell lines. We have synthesised novel acylated derivatives of phloridzin with six different long chain fatty acids by regioselective enzymatic acylation using Candida Antarctica lipase B. The antiproliferative effects of the new compounds were investigated in comparison with the parent compounds, phloridzin, aglycone phloretin, the six free fatty acids and chemotherapeutic drugs (sorafenib, doxorubicin and daunorubicin using human hepatocellular carcinoma HepG2 cells, human breast adenocarcinoma MDA-MB-231 cells and acute monocytic leukemia THP-1 cells along with normal human and rat hepatocytes. The fatty acid esters of phloridzin inhibited significantly the growth of the two carcinoma and leukemia cells while similar treatment doses were not toxic to normal human or rat hepatocytes. The antiproliferative potency of fatty esters of phloridzin was comparable to the potency of the chemotherapeutic drugs. The fatty acid esters of phloridzin inhibited DNA topoisomerases IIα activity that might induce G0/G1 phase arrest, induced apoptosis via activation of caspase-3, and decreased ATP level and mitochondrial membrane potential in HepG2 cells. Based on the high selectivity on cancer cells, decosahexaenoic acid (DHA ester of phloridzin was selected for gene expression analysis using RT2PCR human cancer drug target array. Antiproliferative effect of DHA ester of phloridzin could be related to the down regulation of anti-apoptotic gene (BCL2, growth factor receptors (EBFR family, IGF1R/IGF2, PDGFR and its downstream signalling partners (PI3k/AKT/mTOR, Ras/Raf/MAPK, cell cycle machinery (CDKs, TERT, TOP2A, TOP2B as well as epigenetics regulators (HDACs. These results suggest that fatty esters of phloridzin have potential chemotherapeutic effects

  4. Depression Disturbs Germany

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The suicide of Robert Enke,the goalkeeper of the Germany national football team who had battled depression for years,stunned the country and cast depression into the national spotlight as a disturbing disease.

  5. Sudden Ionospheric Disturbances (SID)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Sudden ionospheric disturbances (SID) are caused by solar flare enhanced X-rays in the 1 to 10 angstrom range. Solar flares can produce large increases of ionization...

  6. Altered Cytokine Production By Specific Human Peripheral Blood Cell Subsets Immediately Following Spaceflight

    Science.gov (United States)

    Crucian, Brian E.; Cubbage, Michael L.; Sams, Clarence F.

    1999-01-01

    In this study, we have attempted to combine standard immunological assays with the cellular resolving power of the flow cytometer to positively identify the specific cell types involved in spaceflight-induced immune alterations. We have obtained whole blood samples from 27 astronauts collected at three timepoints (L-10, R+0 and R+3) surrounding four recent space shuttle missions. The duration of these missions ranged from 10 to 18 days. Assays performed included serum/urine cortisol, comprehensive subset phenotyping, assessment of cellular activation markers and intracellular cytokine production following mitogenic stimulation. Absolute levels of peripheral granulocytes were significantly elevated following spaceflight, but the levels of circulating lymphocytes and monocytes were unchanged. Lymphocyte subset analysis demonstrated trends towards a decreased percentage of T cells and an increased percentage of B cells. Nearly all of the astronauts exhibited an increased CD4:CD8 ratio, which was dramatic in some individuals. Assessment of memory (CD45RA+) vs. naive (CD45RO+) CD4+ T cell subsets was more ambiguous, with subjects tending to group more as a flight crew. All subjects from one mission demonstrated an increased CD45RA:CD45RO ratio, while all subjects from another Mission demonstrated a decreased ratio. While no significant trend was seen in the monocyte population as defined by scatter, a decreased percentage of the CD14+ CD16+ monocyte subset was seen following spaceflight in all subjects tested. In general, most of the cellular changes described above which were assessed at R+O and compared to L-10 trended to pre-flight levels by R+3. Although no significant differences were seen in the expression of the cellular activation markers CD69 and CD25 following exposure to microgravity, significant alterations were seen in cytokine production in response to mitogenic activation for specific subsets. T cell (CD3+) production of IL-2 was significantly decreased

  7. Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum

    Directory of Open Access Journals (Sweden)

    Jochen Hinkelbein

    2017-08-01

    Full Text Available Hypobaric hypoxia (HH during airline travel induces several (patho- physiological reactions in the human body. Whereas severe hypoxia is investigated thoroughly, very little is known about effects of moderate or short-term hypoxia, e.g. during airline flights. The aim of the present study was to analyse changes in serum protein expression and activation of signalling cascades in human volunteers staying for 30 min in a simulated altitude equivalent to airline travel. After approval of the local ethics committee, 10 participants were exposed to moderate hypoxia (simulation of 2400 m or 8000 ft for 30 min in a hypobaric pressure chamber. Before and after hypobaric hypoxia, serum was drawn, centrifuged, and analysed by two-dimensional gel electrophoresis (2-DIGE and matrix-assisted laser desorption/ionization followed by time-of-flight mass spectrometry (MALDI-TOF. Biological functions of regulated proteins were identified using functional network analysis (GeneMania®, STRING®, and Perseus® software. In participants, oxygen saturation decreased from 98.1 ± 1.3% to 89.2 ± 1.8% during HH. Expression of 14 spots (i.e., 10 proteins: ALB, PGK1, APOE, GAPDH, C1QA, C1QB, CAT, CA1, F2, and CLU was significantly altered. Bioinformatic analysis revealed an association of the altered proteins with the signalling cascades “regulation of haemostasis” (four proteins, “metabolism” (five proteins, and “leukocyte mediated immune response” (five proteins. Even though hypobaric hypoxia was short and moderate (comparable to an airliner flight, analysis of protein expression in human subjects revealed an association to immune response, protein metabolism, and haemostasis

  8. Postural stability is altered by the stimulation of pain but not warm receptors in humans

    Directory of Open Access Journals (Sweden)

    Corbeil Philippe

    2003-10-01

    -noxious stimulation (40 degrees C of the small diameter afferents is not a sufficiently intense sensory stimulation to alter the control of posture. A painful stimulation (45 degrees C of the skin thermoreceptors, however, yielded a deterioration of the postural control system. The observed deteriorating effects of the combined stimulation of nociceptors and Ia afferents (when ankle tendons were vibrated could result from the convergence of these afferents at the spinal level. This could certainly lead to the hypothesis that individuals suffering from lower limb pain present alterations of the postural control mechanisms; especially populations already at risk of falling (for example, frail elderly or populations suffering from concomitant lower limb pain and sensory deficits (for example, diabetic polyneuropathy.

  9. Nicotine-induced alterations in the expression of nicotinic receptors in primary cultures from human prenatal brain.

    Science.gov (United States)

    Hellström-Lindahl, E; Seiger A; Kjaeldgaard, A; Nordberg, A

    2001-01-01

    The nicotinic receptor proteins and gene transcripts for the different nicotinic receptor subunits exist in human prenatal brain already at 4-5 weeks of gestation. The early presence of nicotinic receptors suggests an important role for these receptors in modulating dendritic outgrowth, establishment of neuronal connections and synaptogenesis during development. When measurements of nicotinic receptors using [(3)H]epibatidine (labelling both the alpha3 and alpha4 subtype) and [(3)H]cytisine (labelling the alpha4 subtype) were performed in intact cells from the cortex, subcortical forebrain and mesencephalon (7.5-11 weeks of gestation), the highest specific binding for both ligands was detected in cells from mesencephalon, followed by subcortical forebrain and cortex. The effects of nicotine exposure were studied in primary cultures of prenatal brain (7.5-11 weeks of gestation). Treatment with nicotine (1-100 microM) for 3 days significantly increased the specific binding of [(3)H]epibatidine and [(3)H]cytisine in cortical cells but not in cells from subcortical forebrain and mesencephalon brain regions, indicating region-specific differences in the sensitivity to nicotine exposure. Relative quantification of mRNA showed that the expression of the nicotinic receptor subunits alpha3 and alpha7, but not alpha4, was increased in cortical cells after nicotine treatment. These findings support the assumption of a potential risk of disturbance in the functional role of nicotinic receptors during brain development as a consequence of maternal smoking during pregnancy.

  10. Relationship between TLR4 signalling alterations and effective human cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Germini D.

    2014-09-01

    Full Text Available Toll-like receptors (TLR, the main class of immune-sensor molecules triggering the innate immunity pathways, are known to be involved in the infection of different RNA and DNA viruses, including herpesviruses. Human cytomegalovirus (HCMV is a widespread human beta-herpesvirus that infects 80–90 % of the world’s population and it can cause severe and even fatal diseases in immunocompromised patients and it is also responsible for birth defects as a consequence of congenital infection. Aim of this review is to discuss the existing data regarding the role of TLRs in HCMV concentrating mainly on TLR4. A better understanding in this relationship could be exploited for the development of efficient early diagnosis methodologies and anti viral therapies.

  11. Securitization, alterity, and the state Human (in)security on an Amazonian frontier.

    Science.gov (United States)

    Brightman, Marc; Grotti, Vanessa

    2014-12-01

    Focusing on the region surrounding the Maroni River, which forms the border between Suriname and French Guiana, we examine how relations between different state and non-state social groups are articulated in terms of security. The region is characterised by multiple "borders" and frontiers of various kinds, the state boundary having the features of an interface or contact zone. Several key collectivities meet in this border zone: native Amazonians, tribal Maroon peoples, migrant Brazilian gold prospectors, and metropolitan French state functionaries. We explore the relationships between these different sets of actors and describe how their mutual encounters center on discourses of human and state security, thus challenging the commonly held view of the region as a stateless zone and showing that the "human security" of citizens from the perspective of the state may compete with locally salient ideas or experiences of well-being.

  12. Increasing Human Neural Stem Cell Transplantation Dose Alters Oligodendroglial and Neuronal Differentiation after Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Katja M. Piltti

    2017-06-01

    Full Text Available Multipotent human central nervous system-derived neural stem cells transplanted at doses ranging from 10,000 (low to 500,000 (very high cells differentiated predominantly into the oligodendroglial lineage. However, while the number of engrafted cells increased linearly in relationship to increasing dose, the proportion of oligodendrocytic cells declined. Increasing dose resulted in a plateau of engraftment, enhanced neuronal differentiation, and increased distal migration caudal to the transplantation sites. Dose had no effect on terminal sensory recovery or open-field locomotor scores. However, total human cell number and decreased oligodendroglial proportion were correlated with hindlimb girdle coupling errors. Conversely, greater oligodendroglial proportion was correlated with increased Ab step pattern, decreased swing speed, and increased paw intensity, consistent with improved recovery. These data suggest that transplant dose, and/or target niche parameters can regulate donor cell engraftment, differentiation/maturation, and lineage-specific migration profiles.

  13. Propionibacterium acnes inhibits FOXM1 and induces cell cycle alterations in human primary prostate cells

    DEFF Research Database (Denmark)

    Sayanjali, Behnam; Christensen, Gitte J M; Al-Zeer, Munir A;

    2016-01-01

    Propionibacterium acnes has been detected in diseased human prostate tissue, and cell culture experiments suggest that the bacterium can establish a low-grade inflammation. Here, we investigated its impact on human primary prostate epithelial cells. Microarray analysis confirmed the inflammation......-inducing capability of P. acnes but also showed deregulation of genes involved in the cell cycle. qPCR experiments showed that viable P. acnes downregulates a master regulator of cell cycle progression, FOXM1. Flow cytometry experiments revealed that P. acnes increases the number of cells in S-phase. We tested...... the hypothesis that a P. acnes-produced berninamycin-like thiopeptide is responsible for this effect, since it is related to the FOXM1 inhibitor siomycin. The thiopeptide biosynthesis gene cluster was strongly expressed; it is present in subtype IB of P. acnes, but absent from type IA, which is most abundant...

  14. Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity.

    Directory of Open Access Journals (Sweden)

    Monika B Dolinska

    Full Text Available BACKGROUND: Tyrosinase (TYR catalyzes the rate-limiting, first step in melanin production and its gene (TYR is mutated in many cases of oculocutaneous albinism (OCA1, an autosomal recessive cause of childhood blindness. Patients with reduced TYR activity are classified as OCA1B; some OCA1B mutations are temperature-sensitive. Therapeutic research for OCA1 has been hampered, in part, by the absence of purified, active, recombinant wild-type and mutant human enzymes. METHODOLOGY/PRINCIPAL FINDINGS: The intra-melanosomal domain of human tyrosinase (residues 19-469 and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced in T. ni larvae. The short trans-membrane fragment was deleted to avoid potential protein insolubility, while preserving all other functional features of the enzymes. Purified tyrosinase was obtained with a yield of >1 mg per 10 g of larval biomass. The protein was a monomeric glycoenzyme with maximum enzyme activity at 37°C and neutral pH. The two purified mutants when compared to the wild-type protein were less active and temperature sensitive. These differences are associated with conformational perturbations in secondary structure. CONCLUSIONS/SIGNIFICANCE: The intramelanosomal domains of recombinant wild-type and mutant human tyrosinases are soluble monomeric glycoproteins with activities which mirror their in vivo function. This advance allows for the structure - function analyses of different mutant TYR proteins and correlation with their corresponding human phenotypes; it also provides an important tool to discover drugs that may improve tyrosinase activity and treat OCA1.

  15. Cytogenetic and oxidative alterations after exposure of cultured human whole blood cells to lithium metaborate dehydrate.

    Science.gov (United States)

    Çelikezen, Fatih Çağlar; Toğar, Başak; Özgeriş, Fatma Betül; İzgi, Mehmet Sait; Türkez, Hasan

    2016-08-01

    Boron compounds have an ability of supporting antioxidant properties in human and animal tissues. Lithium metaborate dihydrate (LiBO2·2H2O; LMD) is commonly used in nonlinear optic materials, cellular phones and pagers. But, there are limited data on the genotoxic and antioxidant effects of LMD in cultured human whole blood cells. The aim of this study was to evaluate for the genotoxicity and antioxidant/oxidant activity of LMD on human whole blood lymphocytes (n = 5). LMD was applied at various concentrations (0-1,280 µg/ml) to cultured blood samples. Antioxidant/oxidant activity was evaluated by measuring the total oxidant status (TOS) and total antioxidant capacity levels. Micronuclei and chromosomal aberration tests were used in genotoxicity studies. Our results clearly revealed that all tested concentrations of LMD were found to be non-genotoxic when compared to that of the control group. In addition, LMD exhibited antioxidant activities at low concentrations. In addition the TOS levels were not changed at all concentrations of LMD. Consequently, our results clearly demonstrated that LMD is non-genotoxic and it has an important antioxidant potential in vitro.

  16. Propionibacterium acnes inhibits FOXM1 and induces cell cycle alterations in human primary prostate cells.

    Science.gov (United States)

    Sayanjali, Behnam; Christensen, Gitte J M; Al-Zeer, Munir A; Mollenkopf, Hans-Joachim; Meyer, Thomas F; Brüggemann, Holger

    2016-11-01

    Propionibacterium acnes has been detected in diseased human prostate tissue, and cell culture experiments suggest that the bacterium can establish a low-grade inflammation. Here, we investigated its impact on human primary prostate epithelial cells. Microarray analysis confirmed the inflammation-inducing capability of P. acnes but also showed deregulation of genes involved in the cell cycle. qPCR experiments showed that viable P. acnes downregulates a master regulator of cell cycle progression, FOXM1. Flow cytometry experiments revealed that P. acnes increases the number of cells in S-phase. We tested the hypothesis that a P. acnes-produced berninamycin-like thiopeptide is responsible for this effect, since it is related to the FOXM1 inhibitor siomycin. The thiopeptide biosynthesis gene cluster was strongly expressed; it is present in subtype IB of P. acnes, but absent from type IA, which is most abundant on human skin. A knock-out mutant lacking the gene encoding the berninamycin-like peptide precursor was unable to downregulate FOXM1 and to halt the cell cycle. Our study reveals a novel host cell-interacting activity of P. acnes.

  17. Nonthermal sensory input and altered human thermoregulation: effects of visual information depicting hot or cold environments

    Science.gov (United States)

    Takakura, Jun'ya; Nishimura, Takayuki; Choi, Damee; Egashira, Yuka; Watanuki, Shigeki

    2015-10-01

    A recent study showed that thermoregulatory-like cardiovascular responses can be invoked simply by exposure to visual information, even though the thermal environments are neutral and unchanged. However, it was not clear how such responses affect actual human body temperature regulation. We investigated whether such visually invoked physiological responses can substantively affect human core body temperature in a thermally challenging cold environment. Participants comprised 13 graduate or undergraduate students viewing different video images containing hot, cold, or no scenery, while room temperature was gradually lowered from 28 to 16 °C over 80 min. Rectal temperature, mean skin temperature, core to skin temperature gradient, and oxygen consumption were measured during the experiment. Rectal temperature was significantly lower when hot video images were presented compared to when control video images were presented. Oxygen consumption was comparable among all video images, but core to skin temperature gradient was significantly lower when hot video images were presented. This result suggests that visual information, even in the absence of thermal energy, can affect human thermodynamics and core body temperature.

  18. ALTERATION OF CHOLESTEROL SULFATE IN HUMAN SERA DURING THE COURSE OF PREGNANCY

    Institute of Scientific and Technical Information of China (English)

    林蓓; 张淑兰; 岩森正男

    2004-01-01

    Objective To determine the concentrations of cholesterol sulfate (CS) in human sera and placental villi during the course of pregnancy. And to analyze its inhibitory activity on thrombin and further characterize the functional significance of CS. Methods The concentrations of CS were determined by thin-layer chromatography (TLC) on 60 cases of normal pregnant women and 30 cases of normal placental villi. The effect of CS in human sera on the activity of thrombin was analyzed. Results The concentrations of CS in human sera gradually increased from the first to third trimester of gestation with a correlation coefficient of 0.69, and a correlation between the concentration of CS and weeks of gestation (P <0.01 ). CS was also contained in the placental villi, and its concentrations at the second and third trimester of gestations were 4. 7 and 6. 2-fold of that at the first trimester of gestation. CS inhibited the activity of thrombin. Conclusion Placental CS is one of the sources of CS in the serum, probably by shedding. From the observation that CS inhibited the activity of thrombin, the increased expression of CS may play an important role in the regulation of blood coagulation during the course of pregnancy.

  19. Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

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    McIntyre Bradley W

    2005-04-01

    Full Text Available Abstract Background Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis in human osteosarcoma would result in resistance to chemotherapy. Methods Osteosarcoma cell lines (SAOS-2 and TE-85 obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining. Results Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended. Moreover, suspended anoikis resistant TE-85 cells (TE-85ar retained their sensitivity to chemotherapy as well. Conclusion Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators.

  20. Alteration of a human intestinal microbiota under extreme life environment in the Antarctica.

    Science.gov (United States)

    Jin, Jong-Sik; Touyama, Mutsumi; Yamada, Shin; Yamazaki, Takashi; Benno, Yoshimi

    2014-01-01

    The human intestinal microbiota (HIM) settles from birth and continues to change phenotype by some factors (e.g. host's diet) throughout life. However, the effect of extreme life environment on human HIM composition is not well known. To understand HIM fluctuation under extreme life environment in humans, fecal samples were collected from six Japanese men on a long Antarctic expedition. They explored Antarctica for 3 months and collected their fecal samples at once-monthly intervals. Using terminal restriction fragment length polymorphism (T-RFLP) and real time polymerase chain reaction (PCR) analysis, the composition of HIM in six subjects was investigated. Three subjects presented restoration of HIM after the expedition compared versus before and during the expedition. Two thirds samples collected during the expedition belonged to the same cluster in dendrogram. However, all through the expedition, T-RFLP patterns showed interindividual variability. Especially, Bifidobacterium spp. showed a tendency to decrease during and restore after the expedition. A reduction of Bifidobacterium spp. was observed in five subjects the first 1 month of the expedition. Bacteroides thetaiotaomicron, which is thought to proliferate during emotional stress, significantly decreased in one subject, indicating that other factors in addition to emotional stress may affect the composition of HIM in this study. These findings could be helpful to understand the effect of extreme life environment on HIM.

  1. Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans.

    Science.gov (United States)

    Houtepen, Lotte C; Vinkers, Christiaan H; Carrillo-Roa, Tania; Hiemstra, Marieke; van Lier, Pol A; Meeus, Wim; Branje, Susan; Heim, Christine M; Nemeroff, Charles B; Mill, Jonathan; Schalkwyk, Leonard C; Creyghton, Menno P; Kahn, René S; Joëls, Marian; Binder, Elisabeth B; Boks, Marco P M

    2016-03-21

    DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene (KITLG; cg27512205) showed the strongest association with cortisol stress reactivity (P=5.8 × 10(-6)). Replication was obtained in two independent samples using either blood (N=45, P=0.001) or buccal cells (N=255, P=0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability.

  2. Nonthermal sensory input and altered human thermoregulation: effects of visual information depicting hot or cold environments.

    Science.gov (United States)

    Takakura, Jun'ya; Nishimura, Takayuki; Choi, Damee; Egashira, Yuka; Watanuki, Shigeki

    2015-10-01

    A recent study showed that thermoregulatory-like cardiovascular responses can be invoked simply by exposure to visual information, even though the thermal environments are neutral and unchanged. However, it was not clear how such responses affect actual human body temperature regulation. We investigated whether such visually invoked physiological responses can substantively affect human core body temperature in a thermally challenging cold environment. Participants comprised 13 graduate or undergraduate students viewing different video images containing hot, cold, or no scenery, while room temperature was gradually lowered from 28 to 16 °C over 80 min. Rectal temperature, mean skin temperature, core to skin temperature gradient, and oxygen consumption were measured during the experiment. Rectal temperature was significantly lower when hot video images were presented compared to when control video images were presented. Oxygen consumption was comparable among all video images, but core to skin temperature gradient was significantly lower when hot video images were presented. This result suggests that visual information, even in the absence of thermal energy, can affect human thermodynamics and core body temperature.

  3. Human hemoglobin structural and functional alterations and heme degradation upon interaction with benzene: A spectroscopic study

    Science.gov (United States)

    Hosseinzadeh, Reza; Moosavi-Movahedi, Ali Akbar

    2016-03-01

    Here, the effect of benzene on hemoglobin structure, stability and heme prosthetic group integrity was studied by different methods. These included UV-vis absorption spectrophotometry, normal and synchronous fluorescence techniques, and differential scanning calorimetry (DSC). Our results indicated that benzene has high hemolytic potential even at low concentrations. The UV-vis spectroscopic results demonstrated that benzene altered both the globin chain and the heme prosthetic group of hemoglobin increasing met- and deoxy-Hb, while decreasing oxy-Hb. However, with increasing benzene the concentration of all species decreased due to heme destruction. The spectrophotometric results show that benzene has a high potential for penetrating the hydrophobic pocket of hemoglobin. These results were consistent with the molecular docking simulation results of benzene-hHb. Aggregation and thermal denaturation studies show that the increased benzene concentration induced hemoglobin aggregation with a decrease in stability, which is consistent with the DSC results. Conventional fluorescence spectroscopy revealed that the heme degradation species were produced in the presence of benzene. The results of constant wavelength synchronous fluorescence spectroscopy (CWSFS) indicated that at least five heme-degraded species were produced. Together, our results indicated that benzene has adverse effects on hemoglobin structure and function, and heme degradation.

  4. LDLR expression and localization are altered in mouse and human cell culture models of Alzheimer's disease.

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    Jose F Abisambra

    Full Text Available BACKGROUND: Alzheimer's disease (AD is a chronic neurodegenerative disorder and the most common form of dementia. The major molecular risk factor for late-onset AD is expression of the epsilon-4 allele of apolipoprotein E (apoE, the major cholesterol transporter in the brain. The low-density lipoprotein receptor (LDLR has the highest affinity for apoE and plays an important role in brain cholesterol metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Using RT-PCR and western blotting techniques we found that over-expression of APP caused increases in both LDLR mRNA and protein levels in APP transfected H4 neuroglioma cells compared to H4 controls. Furthermore, immunohistochemical experiments showed aberrant localization of LDLR in H4-APP neuroglioma cells, Abeta-treated primary neurons, and in the PSAPP transgenic mouse model of AD. Finally, immunofluorescent staining of LDLR and of gamma- and alpha-tubulin showed a change in LDLR localization preferentially away from the plasma membrane that was paralleled by and likely the result of a disruption of the microtubule-organizing center and associated microtubule network. CONCLUSIONS/SIGNIFICANCE: These data suggest that increased APP expression and Abeta exposure alters microtubule function, leading to reduced transport of LDLR to the plasma membrane. Consequent deleterious effects on apoE uptake and function will have implications for AD pathogenesis and/or progression.

  5. Matrine alters microRNA expression profiles in SGC-7901 human gastric cancer cells.

    Science.gov (United States)

    Li, Hailong; Xie, Shoupin; Liu, Xiaojun; Wu, Hongyan; Lin, Xingyao; Gu, Jing; Wang, Huping; Duan, Yongqiang

    2014-11-01

    Matrine, a major alkaloid extracted from Sophora flavescens, has been reported to possess antitumor properties in several types of cancers, including gastric cancer. However, its mechanisms of action on gastric cancer remain poorly understood. Dysregulation of microRNAs, a class of small, non-coding, regulatory RNA molecules involved in gene expression, is strongly correlated with cancer. The aim of the present study was to demonstrate that matrine treatment altered miRNA expression in SGC7901 cells. Using miRCURY™ microarray analysis, we identified 128 miRNAs substantially exhibiting >2-fold expression changes in matrine-treated cells relative to their expression levels in untreated cells. RT-qPCR was used to show that the levels of 8 miRNAs whose target genes were clustered in the cell cycle pathway increased, while levels of 14 miRNAs whose target genes were clustered in the MAPK signaling pathway decreased. These results were consistent with those from the miRNA microarray experiment. Bioinformatical analysis revealed that the majority of 57 identified enrichment pathways were highly involved in tumorigenesis. In conclusion, the results demonstrated that matrine induces considerable changes in the miRNA expression profiles of SGC7901 cells, suggesting miRNA microarray combined with RT-qPCR validation and bioinformatical analysis provide a novel and promising approach to identify anticancer targets and the mechanisms of matrine involved.

  6. Alterations in interhemispheric functional and anatomical connectivity are associated with tobacco smoking in humans.

    Science.gov (United States)

    Viswanath, Humsini; Velasquez, Kenia M; Thompson-Lake, Daisy Gemma Yan; Savjani, Ricky; Carter, Asasia Q; Eagleman, David; Baldwin, Philip R; De La Garza, Richard; Salas, Ramiro

    2015-01-01

    Abnormal interhemispheric functional connectivity correlates with several neurologic and psychiatric conditions, including depression, obsessive-compulsive disorder, schizophrenia, and stroke. Abnormal interhemispheric functional connectivity also correlates with abuse of cannabis and cocaine. In the current report, we evaluated whether tobacco abuse (i.e., cigarette smoking) is associated with altered interhemispheric connectivity. To that end, we examined resting state functional connectivity (RSFC) using magnetic resonance imaging (MRI) in short term tobacco deprived and smoking as usual tobacco smokers, and in non-smoker controls. Additionally, we compared diffusion tensor imaging (DTI) in the same subjects to study differences in white matter. The data reveal a significant increase in interhemispheric functional connectivity in sated tobacco smokers when compared to controls. This difference was larger in frontal regions, and was positively correlated with the average number of cigarettes smoked per day. In addition, we found a negative correlation between the number of DTI streamlines in the genual corpus callosum and the number of cigarettes smoked per day. Taken together, our results implicate changes in interhemispheric functional and anatomical connectivity in current cigarette smokers.

  7. Nicotine Alters the Proteome of Two Human Pancreatic Duct Cell Lines

    Science.gov (United States)

    Paulo, Joao A

    2015-01-01

    Context Cigarette smoking is a known risk factor of pancreatic disease. Nicotine - a major cigarette tobacco component - can traffic through the circulatory system and may induce fibrosis and metastasis, hallmarks of chronic pancreatitis and pancreatic adenocarcinoma, respectively. However, at the biomolecular level, particularly in pancreatic research, the effects of nicotine remain unresolved. Methods The effects of nicotine on the proteomes of two pancreatic duct cell lines–an immortalized normal cell line (HPNE) and a cancer cell line (PanC1)- were investigated using mass spectrometry-based proteomics. For each cell line, the global proteomesof cells exposed to nicotine for 24 hrswere compared with untreated cells in triplicate using 6-plex tandem mass tag-based isobaric labeling techniques. Results Over 5,000 proteins were detectedper cell line. Of these, over 900 proteins were differentially abundant with statistical significance (corrected p-value <0.01) upon nicotine treatment, 57 of which were so in both cell lines. Amyloid precursor protein, previously observed to increase expression in pancreatic stellate cells when exposed to nicotine, was also up-regulated in both cell lines.In general, the two cell lines varied in the classes of proteins altered by nicotine treatment, supporting published evidence that nicotine may play different roles in the initiation and progression of pancreatic disease. Conclusions Understanding the underlying mechanisms associating nicotine with pancreatic function is paramount to intervention aiming to retard, arrest, or ameliorate pancreatic disease. PMID:25262714

  8. Ablation of p120-Catenin Altering the Activity of Small GTPase in Human Lung Cancer Cells

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    Nan LIU

    2009-05-01

    Full Text Available Background and objective p120-catenin (p120ctn, a member of the Armadillo gene family, has emerged as an important modulator of small GTPase activities. Therefore, it plays novel roles in tumor malignant phenotype, such as invasion and metastasis, whose mechanism are not well clarified yet. The aim of this study is to explore the roles of p120ctn on the regulation of small GTP family members in lung cancer and the effects to lung cancer invasions andmetastasis. Methods After p120ctn was knocked down by siRNA, in vivo and in vitro analysis was applied to investigate the role and possible mechanism of p120ctn in lung cancer, such as Western Blot, pull-down analysis, and nude mice models. Results p120ctn depletion inactivated RhoA, with the the activity of Cdc42 and Rac1 increased, the invasiveness of lung cancer cells was promoted both in vitro and in vivo . Conclusion p120ctn gene knockdown enhances the metastasis of lung cancer cells, probably by altering expression of small GTPase, such as inactivation of RhoA and activation of Cdc42/Rac1.

  9. Arsenic Alters ATP-Dependent Ca2+ Signaling in Human Airway Epithelial Cell Wound Response

    Science.gov (United States)

    Sherwood, Cara L.; Lantz, R. Clark; Burgess, Jefferey L.; Boitano, Scott

    2011-01-01

    Arsenic is a natural metalloid toxicant that is associated with occupational inhalation injury and contaminates drinking water worldwide. Both inhalation of arsenic and consumption of arsenic-tainted water are correlated with malignant and nonmalignant lung diseases. Despite strong links between arsenic and respiratory illness, underlying cell responses to arsenic remain unclear. We hypothesized that arsenic may elicit some of its detrimental effects on the airway through limitation of innate immune function and, specifically, through alteration of paracrine ATP (purinergic) Ca2+ signaling in the airway epithelium. We examined the effects of acute (24 h) exposure with environmentally relevant levels of arsenic (i.e., arsenic reduces purinergic Ca2+ signaling in a dose-dependent manner and results in a reshaping of the Ca2+ signaling response to localized wounds. We next examined arsenic effects on two purinergic receptor types: the metabotropic P2Y and ionotropic P2X receptors. Arsenic inhibited both P2Y- and P2X-mediated Ca2+ signaling responses to ATP. Both inhaled and ingested arsenic can rapidly reach the airway epithelium where purinergic signaling is essential in innate immune functions (e.g., ciliary beat, salt and water transport, bactericide production, and wound repair). Arsenic-induced compromise of such airway defense mechanisms may be an underlying contributor to chronic lung disease. PMID:21357385

  10. Absorption spectra and light penetration depth of normal and pathologically altered human skin

    Science.gov (United States)

    Barun, V. V.; Ivanov, A. P.; Volotovskaya, A. V.; Ulashchik, V. S.

    2007-05-01

    A three-layered skin model (stratum corneum, epidermis, and dermis) and engineering formulas for radiative transfer theory are used to study absorption spectra and light penetration depths of normal and pathologically altered skin. The formulas include small-angle and asymptotic approximations and a layer-addition method. These characteristics are calculated for wavelengths used for low-intensity laser therapy. We examined several pathologies such as vitiligo, edema, erythematosus lupus, and subcutaneous wound, for which the bulk concentrations of melanin and blood vessels or tissue structure (for subcutaneous wound) change compared with normal skin. The penetration depth spectrum is very similar to the inverted blood absorption spectrum. In other words, the depth is minimal at blood absorption maxima. The calculated absorption spectra enable the power and irradiation wavelength providing the required light effect to be selected. Relationships between the penetration depth and the diffuse reflectance coefficient of skin (unambiguously expressed through the absorption coefficient) are analyzed at different wavelengths. This makes it possible to find relationships between the light fields inside and outside the tissue.

  11. Alterations in Interhemispheric Functional and Anatomical Connectivity are Associated with Tobacco Smoking in Humans

    Directory of Open Access Journals (Sweden)

    Humsini eViswanath

    2015-03-01

    Full Text Available Abnormal interhemispheric functional connectivity correlates with several neurologic and psychiatric conditions, including depression, obsessive-compulsive disorder, schizophrenia, and stroke. Abnormal interhemispheric functional connectivity also correlates with abuse of cannabis and cocaine. In the current report, we evaluated whether tobacco abuse (i.e., cigarette smoking is associated with altered interhemispheric connectivity. To that end, we examined resting state functional connectivity using magnetic resonance imaging (MRI in short term tobacco deprived and smoking as usual tobacco smokers, and in non-smoker controls. Additionally, we compared diffusion tensor imaging (DTI in the same subjects to study differences in white matter. The data reveal a significant increase in interhemispheric functional connectivity in sated tobacco smokers when compared to controls. This difference was larger in frontal regions, and was positively correlated with the average number of cigarettes smoked per day. In addition, we found a negative correlation between the number of DTI streamlines in the genual corpus callosum and the number of cigarettes smoked per day. Taken together, our results implicate changes in interhemispheric functional and anatomical connectivity in current cigarette smokers.

  12. Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans.

    Science.gov (United States)

    Cedernaes, Jonathan; Fanelli, Flaminia; Fazzini, Alessia; Pagotto, Uberto; Broman, Jan-Erik; Vogel, Heike; Dickson, Suzanne L; Schiöth, Helgi B; Benedict, Christian

    2016-12-01

    Following binding to cannabinoid receptors, endocannabinoids regulate a variety of central nervous system processes including appetite and mood. Recent evidence suggests that the systemic release of these lipid metabolites can be altered by acute exercise and that their levels also vary across the 24-h sleep-wake cycle. The present study utilized a within-subject design (involving 16 normal-weight men) to determine whether daytime circulating endocannabinoid concentrations differ following three nights of partial sleep deprivation (4.25-h sleep opportunity, 2:45-7a.m. each night) vs. normal sleep (8.5-h sleep opportunity, 10:30p.m.-7a.m. each night), before and after an acute bout of ergometer cycling in the morning. In addition, subjective hunger and stress were measured. Pre-exercise plasma concentrations of 2-arachidonoylglycerol (2AG) were 80% higher 1.5h after awakening (vs. normal sleep, pexercise (+44%, pduration did not however modulate this exercise-induced rise. Finally, subjective stress was generally lower on the day after three nights of short sleep vs. normal sleep, especially after exercise (pmood, our results could suggest that behavioral effects of acute sleep loss, such as increased hunger and transiently improved psychological state, may partially result from activation of this signaling pathway. In contrast, more pronounced exercise-induced elevations of endocannabinoids appear to be less affected by short sleep duration. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Reduced response to IKr blockade and altered hERG1a/1b stoichiometry in human heart failure.

    Science.gov (United States)

    Holzem, Katherine M; Gomez, Juan F; Glukhov, Alexey V; Madden, Eli J; Koppel, Aaron C; Ewald, Gregory A; Trenor, Beatriz; Efimov, Igor R

    2016-07-01

    Heart failure (HF) claims 250,000 lives per year in the US, and nearly half of these deaths are sudden and presumably due to ventricular tachyarrhythmias. QT interval and action potential (AP) prolongation are hallmark proarrhythmic changes in the failing myocardium, which potentially result from alterations in repolarizing potassium currents. Thus, we aimed to examine whether decreased expression of the rapid delayed rectifier potassium current, IKr, contributes to repolarization abnormalities in human HF. To map functional IKr expression across the left ventricle (LV), we optically imaged coronary-perfused LV free wall from donor and end-stage failing human hearts. The LV wedge preparation was used to examine transmural AP durations at 80% repolarization (APD80), and treatment with the IKr-blocking drug, E-4031, was utilized to interrogate functional expression. We assessed the percent change in APD80 post-IKr blockade relative to baseline APD80 (∆APD80) and found that ∆APD80s are reduced in failing versus donor hearts in each transmural region, with 0.35-, 0.43-, and 0.41-fold reductions in endo-, mid-, and epicardium, respectively (p=0.008, 0.037, and 0.022). We then assessed hERG1 isoform gene and protein expression levels using qPCR and Western blot. While we did not observe differences in hERG1a or hERG1b gene expression between donor and failing hearts, we found a shift in the hERG1a:hERG1b isoform stoichiometry at the protein level. Computer simulations were then conducted to assess IKr block under E-4031 influence in failing and nonfailing conditions. Our results confirmed the experimental observations and E-4031-induced relative APD80 prolongation was greater in normal conditions than in failing conditions, provided that the cellular model of HF included a significant downregulation of IKr. In human HF, the response to IKr blockade is reduced, suggesting decreased functional IKr expression. This attenuated functional response is associated with

  14. Altered endoribonuclease activity of apurinic/apyrimidinic endonuclease 1 variants identified in the human population.

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    Wan Cheol Kim

    Full Text Available Apurinic/apyrimidinic endonuclease 1 (APE1 is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5' to abasic sites. APE1 also has 3'-5' DNA exonuclease and 3' DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76-85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3' of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60-80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality.

  15. Altered endoribonuclease activity of apurinic/apyrimidinic endonuclease 1 variants identified in the human population.

    Science.gov (United States)

    Kim, Wan Cheol; Ma, Conan; Li, Wai-Ming; Chohan, Manbir; Wilson, David M; Lee, Chow H

    2014-01-01

    Apurinic/apyrimidinic endonuclease 1 (APE1) is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5' to abasic sites. APE1 also has 3'-5' DNA exonuclease and 3' DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76-85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3' of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60-80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality.

  16. Preventive effects of tamarind seed coat extract on UVA-induced alterations in human skin fibroblasts.

    Science.gov (United States)

    Phetdee, Khemjira; Rakchai, Racharat; Rattanamanee, Kwanchai; Teaktong, Thanasak; Viyoch, Jarupa

    2014-01-01

    One of the most damaging actions on skin is from solar radiation, particularly from its ultraviolet (UV) component, through the formation of oxidative species. Thus, an antioxidant strategy that prevents the formation of these oxidants could form the basis of an efficacious cutaneous protectant. Many herbal materials contain antioxidant polyphenols, and this study assessed the possibility that tamarind seed coat extract could fulfill this role. An alcoholic extract of the tamarind (Tamarindus indica L.) seed coat showed stronger antioxidant activity (2,2-diphenyl-1-picrylhydrazyl inhibition, EC(50) = 12.9 μg/ml) than L-ascorbic acid (EC(50) = 22.9 μg/ml) and α-tocopherol (EC(50) = 29.3 μg/ml). In cultured fibroblasts taken from human skin, hydrogen peroxide (100-1000 μM) damaged 62-92% of the cells compared to only 35-47% when the cells were preincubated in extract (200 μg/ml) for 24 h. UVA (40 J/cm2) irradiation of human fibroblasts damaged 25% of the cells but the death rate was reduced to 10% with extract. UV irradiation increased the proportion of cells arrest in G(0)/G(1) phase (from 59% to 78%) but this was largely prevented by the extract (64%), according to flow cytometry. Intracellular total glutathione of UVA-irradiated cells pretreated with the extract increased to 10-25% compared to the non-pretreated group at 24-72 h after irradiation. Fibroblasts typically increased matrix metalloproteinase-1 secretion after photodamage, and this is prevented by the extract. This is the first report showing that tamarind seed coat extract is an antioxidant and can protect human skin fibroblasts from cellular damage produced by UVA and thus may form the foundation for an antiaging cosmetic.

  17. Dysfunctional CFTR alters the bactericidal activity of human macrophages against Pseudomonas aeruginosa.

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    Paola Del Porto

    Full Text Available Chronic inflammation of the lung, as a consequence of persistent bacterial infections by several opportunistic pathogens represents the main cause of mortality and morbidity in cystic fibrosis (CF patients. Mechanisms leading to increased susceptibility to bacterial infections in CF are not completely known, although the involvement of cystic fibrosis transmembrane conductance regulator (CFTR in microbicidal functions of macrophages is emerging. Tissue macrophages differentiate in situ from infiltrating monocytes, additionally, mature macrophages from different tissues, although having a number of common activities, exhibit variation in some molecular and cellular functions. In order to highlight possible intrinsic macrophage defects due to CFTR dysfunction, we have focused our attention on in vitro differentiated macrophages from human peripheral blood monocytes. Here we report on the contribution of CFTR in the bactericidal activity against Pseudomonas aeruginosa of monocyte derived human macrophages. At first, by real time PCR, immunofluorescence and patch clamp recordings we demonstrated that CFTR is expressed and is mainly localized to surface plasma membranes of human monocyte derived macrophages (MDM where it acts as a cAMP-dependent chloride channel. Next, we evaluated the bactericidal activity of P. aeruginosa infected macrophages from healthy donors and CF patients by antibiotic protection assays. Our results demonstrate that control and CF macrophages do not differ in the phagocytic activity when infected with P. aeruginosa. Rather, although a reduction of intracellular live bacteria was detected in both non-CF and CF cells, the percentage of surviving bacteria was significantly higher in CF cells. These findings further support the role of CFTR in the fundamental functions of innate immune cells including eradication of bacterial infections by macrophages.

  18. Altered neurotransmission in the lateral amygdala in aged human apoE4 targeted replacement mice.

    Science.gov (United States)

    Klein, Rebecca C; Acheson, Shawn K; Mace, Brian E; Sullivan, Patrick M; Moore, Scott D

    2014-09-01

    The human APOE4 allele is associated with an early age of onset and increased risk of Alzheimer's disease (AD). Apolipoprotein E is secreted as part of a high-density lipoprotein-like particle by glial cells in the brain for the primary purpose of transport of lipophilic compounds involved in the maintenance of synapses. Previous studies examining synaptic integrity in the amygdala of human apoE targeted replacement (TR) mice showed a decrease in spontaneous excitatory synaptic activity, dendritic arbor, and spine density associated with apoE4 compared with apoE3 and apoE2 in adult male mice. In the present study, we assessed how APOE genotype affects synaptic integrity of amygdala neurons by comparing electrophysiological and morphometric properties in human apoE3, E4, and E2/4 TR mice at the age of 18-20 months. In contrast to adult mice, we found that aged apoE4 TR mice exhibited the highest level of excitatory synaptic activity compared with other cohorts. Additionally, apoE4 mice had significantly greater spontaneous inhibitory activity than all other cohorts. Taken together, there was a significant interaction between genotypes when comparing inhibition relative to excitation; there was a simple main effect of frequency type with an imbalance toward inhibition in apoE4 mice but not in apoE3 or apoE2/4 mice. These results suggest that apoE isoforms differentially influence synaptic transmission throughout the life span, where aging coupled with apoE4 expression, results in an imbalance in maintaining integrity of synaptic transmission.

  19. Taxonomic and trait based recolonization dynamics of a riverine fish assemblage following a large scale human mediated disturbance: the red mud disaster in Hungary

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    Tibor Eros

    2015-12-01

    Full Text Available We examined the recovery of a fish assemblage following the catastrophic spill of highly alkaline (pH~13 red sludge into a lowland river (i to characterize taxonomic and trait based colonization of fishes in the river in the first three years of the recovery, and (ii to determine which structural and trait based variables best predicted colonization. Species richness showed comparable values to pre-disturbance state less than one year after the spill. We found only moderate changes in the dominance of the most abundant species between pre- and post-disturbance periods, and consistent changes in the relative abundance of some rare species during the post-disturbance period. Frequency of occurrence (% of the fishes in the watershed, and their relative abundance (% proved to be the most important predictor variables in colonization, whereas trait based variables had a less important role. Our study about one of the largest scale and most serious documented fish kill shows that both taxonomic and trait based structure of fish assemblages can regenerate remarkable fast in a modified river and also shows that unfortunate chemical spills provide insights into the assembly of stream fish assemblages.

  20. Postural Control Disturbances Produced By Exposure to HMD and Dome Vr Systems

    Science.gov (United States)

    Harm, D. L.; Taylor, L. C.

    2005-01-01

    Two critical and unresolved human factors issues in VR systems are: 1) potential "cybersickness", a form of motion sickness which is experienced in virtual worlds, and 2) maladaptive sensorimotor performance following exposure to VR systems. Interestingly, these aftereffects are often quite similar to adaptive sensorimotor responses observed in astronauts during and/or following space flight. Most astronauts and cosmonauts experience perceptual and sensorimotor disturbances during and following space flight. All astronauts exhibit decrements in postural control following space flight. It has been suggested that training in virtual reality (VR) may be an effective countermeasure for minimizing perceptual and/or sensorimotor disturbances. People adapt to consistent, sustained alterations of sensory input such as those produced by microgravity, and experimentally-produced stimulus rearrangements (e.g., reversing prisms, magnifying lenses, flight simulators, and VR systems). Adaptation is revealed by aftereffects including perceptual disturbances and sensorimotor control disturbances. The purpose of the current study was to compare disturbances in postural control produced by dome and head-mounted virtual environment displays. Individuals recovered from motion sickness and the detrimental effects of exposure to virtual reality on postural control within one hour. Sickness severity and initial decrements in postural equilibrium decreases over days, which suggests that subjects become dual-adapted over time. These findings provide some direction for developing training schedules for VR users that facilitate adaptation, and address safety concerns about aftereffects.

  1. Human cytomegalovirus induces alteration of β-actin mRNA and microfilaments in human embryo fibroblast cells

    Institute of Scientific and Technical Information of China (English)

    林茂芳; 魏国庆; 黄河; 蔡真

    2004-01-01

    Objective: To investigate the infection of human embryo fibroblast cell line HF cells by CMV as well as the effects of CMV on β-actin mRNA and microfilaments. Methods: HF cells shape was observed after the infection of CMV.RT-PCR assay was used to detect the mRNA expression of CMV immediate early (IE) gene, β-actin and GAPDH genes of HF cells infected by CMV. CMV particles and cell microfilaments were detected with electron microscope. Results: Shape of HF cell changed after the infection by CMV. HF cells infected by CMV could express IE mRNA and the expression of β-actin mRNA decreased in a time-and titer-dependent manner compared with the uninfected HF cells whose expression of GAPDH mRNA did not change much. CMV particles were found with electron microscope in the cells. Microfilaments were ruptured and shortened after the infection of CMV. Conclusion: CMV can not only infect human embryo fibroblast cells line HF cells and replicate in the cells, but can also affect the expression of β-actin mRNA and the microfilaments.

  2. P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating.

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    Hiroki Takeuchi

    Full Text Available Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI, a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD, in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions.

  3. GESTATIONAL DIABETES MELLITUS ALTERS APOPTOTIC AND INFLAMMATORY GENE EXPRESSION OF TROPHOBASTS FROM HUMAN TERM PLACENTA

    Science.gov (United States)

    MAGEE, Thomas R.; ROSS, Michael G.; WEDEKIND, Lauren; DESAI, Mina; KJOS, Siri; BELKACEMI, Louiza

    2014-01-01

    AIM Increased placental growth secondary to reduced apoptosis may contribute to the development of macrosomia in GDM pregnancies. We hypothesize that reduced apoptosis in GDM placentas is caused by dysregulation of apoptosis related genes from death receptors or mitochondrial pathway or both to enhance placental growth in GDM pregnancies. METHODS Newborn and placental weights from women with no pregnancy complications (controls; N=5), or with GDM (N=5) were recorded. Placental villi from both groups were either fixed for TUNEL assay, or snap frozen for gene expression analysis by apoptosis PCR microarrays and qPCR. RESULTS Maternal, placental and newborn weights were significantly higher in the GDM group vs. Controls. Apoptotic index of placentas from the GDM group was markedly lower than the Controls. At a significant threshold of 1.5, seven genes (BCL10, BIRC6, BIRC7, CASP5, CASP8P2, CFLAR, and FAS) were down regulated, and 13 genes (BCL2, BCL2L1, BCL2L11, CASP4, DAPK1, IκBκE, MCL1, NFκBIZ, NOD1, PEA15, TNF, TNFRSF25, and XIAP) were unregulated in the GDM placentas. qPCR confirmed the consistency of the PCR microarray. Using Western blotting we found significantly decreased placental pro-apoptotic FAS receptor and FAS ligand (FASL), and increased mitochondrial anti-apoptotic BCL2 post GDM insult. Notably, caspase-3, which plays a central role in the execution-phase of apoptosis, and its substrate poly (ADP-ribose) polymerase (PARP) were significantly down regulated in GDM placentas, as compared to non-diabetic Control placentas. CONCLUSION . Women with gestational diabetes (GDM) are at increased risk for having macrosomic newborns, and larger placentas with reduced apoptosis. Decreased apoptosis subsequent to alterations in apoptotic and inflammatory genes may promote elevated weight in the GDM placentas. PMID:24768206

  4. Mitochondrial and Morphologic Alterations in Native Human Corneal Endothelial Cells Associated With Diabetes Mellitus.

    Science.gov (United States)

    Aldrich, Benjamin T; Schlötzer-Schrehardt, Ursula; Skeie, Jessica M; Burckart, Kimberlee A; Schmidt, Gregory A; Reed, Cynthia R; Zimmerman, M Bridget; Kruse, Friedrich E; Greiner, Mark A

    2017-04-01

    To characterize changes in the energy-producing metabolic activity and morphologic ultrastructure of corneal endothelial cells associated with diabetes mellitus. Transplant suitable corneoscleral tissue was obtained from donors aged 50 to 75 years. We assayed 3-mm punches of endothelium-Descemet membrane for mitochondrial respiration and glycolysis activity using extracellular flux analysis of oxygen and pH, respectively. Transmission electron microscopy was used to assess qualitative and quantitative ultrastructural changes in corneal endothelial cells and associated Descemet membrane. For purposes of analysis, samples were divided into four groups based on a medical history of diabetes regardless of type: (1) nondiabetic, (2) noninsulin-dependent diabetic, (3) insulin-dependent diabetic, and (4) insulin-dependent diabetic with specified complications due to diabetes (advanced diabetic). In total, 229 corneas from 159 donors were analyzed. Insulin-dependent diabetic samples with complications due to diabetes displayed the lowest spare respiratory values compared to all other groups (P ≤ 0.002). The remaining mitochondrial respiration and glycolysis metrics did not differ significantly among groups. Compared to nondiabetic controls, the endothelium from advanced diabetic samples had alterations in mitochondrial morphology, pronounced Golgi bodies associated with abundant vesicles, accumulation of lysosomal bodies/autophagosomes, and focal production of abnormal long-spacing collagen. Extracellular flux analysis suggests that corneal endothelial cells of donors with advanced diabetes have impaired mitochondrial function. Metabolic findings are supported by observed differences in mitochondrial morphology of advanced diabetic samples but not controls. Additional studies are needed to determine the precise mechanism(s) by which mitochondria become impaired in diabetic corneal endothelial cells.

  5. Altered Proteome of Burkholderia pseudomallei Colony Variants Induced by Exposure to Human Lung Epithelial Cells.

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    Anis Rageh Al-Maleki

    Full Text Available Burkholderia pseudomallei primary diagnostic cultures demonstrate colony morphology variation associated with expression of virulence and adaptation proteins. This study aims to examine the ability of B. pseudomallei colony variants (wild type [WT] and small colony variant [SCV] to survive and replicate intracellularly in A549 cells and to identify the alterations in the protein expression of these variants, post-exposure to the A549 cells. Intracellular survival and cytotoxicity assays were performed followed by proteomics analysis using two-dimensional gel electrophoresis. B. pseudomallei SCV survive longer than the WT. During post-exposure, among 259 and 260 protein spots of SCV and WT, respectively, 19 were differentially expressed. Among SCV post-exposure up-regulated proteins, glyceraldehyde 3-phosphate dehydrogenase, fructose-bisphosphate aldolase (CbbA and betaine aldehyde dehydrogenase were associated with adhesion and virulence. Among the down-regulated proteins, enolase (Eno is implicated in adhesion and virulence. Additionally, post-exposure expression profiles of both variants were compared with pre-exposure. In WT pre- vs post-exposure, 36 proteins were differentially expressed. Of the up-regulated proteins, translocator protein, Eno, nucleoside diphosphate kinase (Ndk, ferritin Dps-family DNA binding protein and peptidyl-prolyl cis-trans isomerase B were implicated in invasion and virulence. In SCV pre- vs post-exposure, 27 proteins were differentially expressed. Among the up-regulated proteins, flagellin, Eno, CbbA, Ndk and phenylacetate-coenzyme A ligase have similarly been implicated in adhesion, invasion. Protein profiles differences post-exposure provide insights into association between morphotypic and phenotypic characteristics of colony variants, strengthening the role of B. pseudomallei morphotypes in pathogenesis of melioidosis.

  6. Prognostic implications of RB1 tumour suppressor gene alterations in the clinical outcome of human osteosarcoma: a meta-analysis.

    Science.gov (United States)

    Ren, W; Gu, G

    2017-01-01

    Primary osteosarcoma is the most frequent malignant bone cancer in children and teenagers. Genetic alterations at the retinoblastoma 1 (RB1) gene has been implicated in the development and progression of human osteosarcoma. Here, we performed a meta-analysis to examine the impact of RB1 mutations on the survival of osteosarcoma patients, the risk of metastasis and the histological response of osteosarcoma to chemotherapy. A systemic review of the Medline, Embase, Scopus and Cochrane Library yielded 12 eligible studies with 491 patients for this study. Forest plots resulting from our meta-analyses illustrate that loss of RB1 function results in a 1.62-fold increase in the mortality rate for osteosarcoma patients (RR = 1.62, 95% CI: 1.23-2.13; Z = 3.44, P = 0.0006), a significant increase in osteosarcoma metastasis (OR = 3.95, 95% CI: 1.86-8.38; Z = 3.57; P = 0.0004), and a significant reduction in the histological response of osteosarcoma to chemotherapy (OR = 0.35; 95% CI: 0.13-0.94; Z = -2.08; P = 0.038). Additionally, the nearly symmetrical funnel plot (Egger's test, t = 1.15, P = 0.288) indicates absence of publication bias regarding the meta-analysis that examined the correlation of RB1 alterations with the survival rate for osteosarcoma patients. Our findings suggest that RB1 alterations may serve as a prognostic marker for the management of osteosarcoma patients. © 2015 John Wiley & Sons Ltd.

  7. Hydrochloric acid alters the effect of L-glutamic acid on cell viability in human neuroblastoma cell cultures.

    Science.gov (United States)

    Croce, Nicoletta; Bernardini, Sergio; Di Cecca, Stefano; Caltagirone, Carlo; Angelucci, Francesco

    2013-07-15

    l-Glutamic acid (l-glutamate) is used to induce excitotoxicity and test neuroprotective compounds in cell cultures. However, because l-glutamate powder is nearly insoluble in water, many manufacturers recommend reconstituting l-glutamate in hydrochloric acid (HCl) prior to successive dilutions. Nevertheless, HCl, even at low concentrations, may alter the pH of the cell culture medium and interfere with cell activity. Thus, the aim of this study was to evaluate whether the reconstitution of l-glutamate powder in HCl alters its capacity to induce neurotoxicity in different human neuroblastoma cell lines. SH-SY5Y, IMR-32 and SK-N-BE(2) cells were exposed to various concentrations of l-glutamate, which was either reconstituted in HCl (1M) or post re-equilibrated to the pH of the culture medium (7.5). After 24 and 48h of incubation, changes in the cell viability of treated versus untreated cells were evaluated. The effect of an identical amount of HCl present in the l-glutamate dilutions on neuroblastoma cell survival was also investigated. Our data showed that the neurotoxicity of glutamate reconstituted in HCl was comparable to that of HCl alone. Moreover, the pH variations induced by glutamate or HCl in the culture medium were similar. When the pH of the glutamate stock solution was re-equilibrated, l-glutamate induced variation in cell viability to a lower extent and after a longer incubation time. This study demonstrated that HCl used to reconstitute l-glutamate powder might alter the effect of glutamate itself in neuroblastoma cell cultures. Thus, this information might be useful to scientists who use l-glutamate to induce excitotoxicity or to test neuroprotective agents.

  8. Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure

    Science.gov (United States)

    Sokolov, Mykyta; Neumann, Ronald

    2015-01-01

    Exposure to ionizing radiation (IR) is inevitable to humans in real-life scenarios; the hazards of IR primarily stem from its mutagenic, carcinogenic, and cell killing ability. For many decades, extensive research has been conducted on the human cell responses to IR delivered at a low dose/low dose (LD) rate. These studies have shown that the molecular-, cellular-, and tissue-level responses are different after low doses of IR (LDIR) compared to those observed after a short-term high-dose IR exposure (HDIR). With the advent of high-throughput technologies in the late 1990s, such as DNA microarrays, changes in gene expression have also been found to be ubiquitous after LDIR. Very limited subset of genes has been shown to be consistently up-regulated by LDIR, including CDKN1A. Further research on the biological effects and mechanisms induced by IR in human cells demonstrated that the molecular and cellular processes, including transcriptional alterations, activated by LDIR are often related to protective responses and, sometimes, hormesis. Following LDIR, some distinct responses were observed, these included bystander effects, and adaptive responses. Changes in gene expression, not only at the level of mRNA, but also miRNA, have been found to crucially underlie these effects having implications for radiation protection purposes. PMID:26729107

  9. Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Mykyta Sokolov

    2015-12-01

    Full Text Available Exposure to ionizing radiation (IR is inevitable to humans in real-life scenarios; the hazards of IR primarily stem from its mutagenic, carcinogenic, and cell killing ability. For many decades, extensive research has been conducted on the human cell responses to IR delivered at a low dose/low dose (LD rate. These studies have shown that the molecular-, cellular-, and tissue-level responses are different after low doses of IR (LDIR compared to those observed after a short-term high-dose IR exposure (HDIR. With the advent of high-throughput technologies in the late 1990s, such as DNA microarrays, changes in gene expression have also been found to be ubiquitous after LDIR. Very limited subset of genes has been shown to be consistently up-regulated by LDIR, including CDKN1A. Further research on the biological effects and mechanisms induced by IR in human cells demonstrated that the molecular and cellular processes, including transcriptional alterations, activated by LDIR are often related to protective responses and, sometimes, hormesis. Following LDIR, some distinct responses were observed, these included bystander effects, and adaptive responses. Changes in gene expression, not only at the level of mRNA, but also miRNA, have been found to crucially underlie these effects having implications for radiation protection purposes.

  10. mTORC1 Inhibition Corrects Neurodevelopmental and Synaptic Alterations in a Human Stem Cell Model of Tuberous Sclerosis.

    Science.gov (United States)

    Costa, Veronica; Aigner, Stefan; Vukcevic, Mirko; Sauter, Evelyn; Behr, Katharina; Ebeling, Martin; Dunkley, Tom; Friedlein, Arno; Zoffmann, Sannah; Meyer, Claas A; Knoflach, Frédéric; Lugert, Sebastian; Patsch, Christoph; Fjeldskaar, Fatiha; Chicha-Gaudimier, Laurie; Kiialainen, Anna; Piraino, Paolo; Bedoucha, Marc; Graf, Martin; Jessberger, Sebastian; Ghosh, Anirvan; Bischofberger, Josef; Jagasia, Ravi

    2016-04-05

    Hyperfunction of the mTORC1 pathway has been associated with idiopathic and syndromic forms of autism spectrum disorder (ASD), including tuberous sclerosis, caused by loss of either TSC1 or TSC2. It remains largely unknown how developmental processes and biochemical signaling affected by mTORC1 dysregulation contribute to human neuronal dysfunction. Here, we have characterized multiple stages of neurogenesis and synapse formation in human neurons derived from TSC2-deleted pluripotent stem cells. Homozygous TSC2 deletion causes severe developmental abnormalities that recapitulate pathological hallmarks of cortical malformations in patients. Both TSC2(+/-) and TSC2(-/-) neurons display altered synaptic transmission paralleled by molecular changes in pathways associated with autism, suggesting the convergence of pathological mechanisms in ASD. Pharmacological inhibition of mTORC1 corrects developmental abnormalities and synaptic dysfunction during independent developmental stages. Our results uncouple stage-specific roles of mTORC1 in human neuronal development and contribute to a better understanding of the onset of neuronal pathophysiology in tuberous sclerosis.

  11. Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection.

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    Yoichiro Shibata

    2012-06-01

    Full Text Available Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species.

  12. P53 alters the cytotoxicity and genotoxicity for oxidized graphene in human B-lymphoblastoid cells

    Science.gov (United States)

    Petibone, Dayton Matthew

    Widespread use of oxidized graphene nanomaterials in industry, medicine, and consumer products raises concern about potential adverse impacts on human health. The p53 tumor suppressor protein is crucial to maintaining cellular and genetic stability to prevent carcinogenesis. Here, we show that oxygen functionalized graphene (f-G) absorption and p53 functional status correlate with cytotoxicity and genotoxicity in human B-lymphoblastoid cells. Trends in f-G absorption by were dose-dependent. Cells with functional p53 exposed to f-G arrested in G0/G1 phase of the cell cycle, suppressed f-G induced reactive oxygen species (ROS), and had elevated apoptosis. While compared to p53 competent cells, the p53 deficient cells exposed to f-G accumulated in S-phase of the cell cycle, had elevated ROS levels, and evaded apoptosis. The f-G genotoxicity was evident as increased loss-of-heterozygosity mutants independent of p53 status, and structural chromosome damage in p53 deficient cells. These findings have broad implications for the safety and efficacy of oxidized graphene nanomaterials in industrial, consumer products and biomedical applications.

  13. Altered temporal dynamics of neural adaptation in the aging human auditory cortex.

    Science.gov (United States)

    Herrmann, Björn; Henry, Molly J; Johnsrude, Ingrid S; Obleser, Jonas

    2016-09-01

    Neural response adaptation plays an important role in perception and cognition. Here, we used electroencephalography to investigate how aging affects the temporal dynamics of neural adaptation in human auditory cortex. Younger (18-31 years) and older (51-70 years) normal hearing adults listened to tone sequences with varying onset-to-onset intervals. Our results show long-lasting neural adaptation such that the response to a particular tone is a nonlinear function of the extended temporal history of sound events. Most important, aging is associated with multiple changes in auditory cortex; older adults exhibit larger and less variable response magnitudes, a larger dynamic response range, and a reduced sensitivity to temporal context. Computational modeling suggests that reduced adaptation recovery times underlie these changes in the aging auditory cortex and that the extended temporal stimulation has less influence on the neural response to the current sound in older compared with younger individuals. Our human electroencephalography results critically narrow the gap to animal electrophysiology work suggesting a compensatory release from cortical inhibition accompanying hearing loss and aging.

  14. Alterations in interferon-gamma and nitric oxide levels in human echinococcosis.

    Science.gov (United States)

    Ait Aissa, S; Amri, M; Bouteldja, R; Wietzerbin, J; Touil-Boukoffa, C

    2006-05-15

    Human cystic hydatid disease is characterized by the long-term coexistence of Echinococcus granulosus and its host without effective rejection of the parasite. This parasitic helminth infection currently constitutes a major health problem in Algeria. We investigated interferon-gamma (IFN-gamma) and nitrite (NO2-) production in PBMC culture 2 supernatants from Algerian patients (n = 35), stimulated by a major antigen (antigen 5). Nitrite was also observed in 74 sera and 28 cyst fluids of patients carrying cysts in different locations. In addition, we report the detection of Nitric Oxide Synthase-2 (NOS2) in liver biopsies of patients (n = 8) by an immunochemical method using human NOS2 antibody. In vivo nitrite levels in host sera and cyst biological fluid point to a tight relation between host response and macro-parasite effects. Our in vitro results indicate a correlation between nitrite and IFN-gamma production in PBMC culture supernatants. Furthermore, by immunohistochemistry NOS2 expression was observed in hepatocytes and Küpffer cells from hydatid patients. Collectively, our data imply NO production in host defense against the extracellular parasite, probably in response to an IFN-gamma activating signal. Concomitant enhanced levels of IFN-gamma and nitrite represent useful indicators of the clinical aggressiveness of hydatidosis.

  15. Biochemically altered human erythrocytes as a carrier for targeted delivery of primaquine: an in vitro study.

    Science.gov (United States)

    Alanazi, Fars K; Harisa, Gamal El-Din I; Maqboul, Ahmad; Abdel-Hamid, Magdi; Neau, Steven H; Alsarra, Ibrahim A

    2011-04-01

    The aim of this study was to investigate human erythrocytes as a carrier for targeted drug delivery of primaquine (PQ). The process of PQ loading in human erythrocytes, as well as the effect of PQ loading on the oxidative status of erythrocytes, was also studied. At PQ concentrations of 2, 4, 6, and 8 mg/mL and an incubation time of 2 h, the ratios of the concentrations of PQ entrapped in erythrocytes to that in the incubation medium were 0.515, 0.688, 0.697 and 0.788, respectively. The maximal decline of erythrocyte reduced glutathione content was observed at 8 mg/mL of PQ compared with native erythrocytes p erythrocytes was increased in comparison with unloaded cells. Electron microscopy revealed spherocyte formation with PQ carrier erythrocytes. PQ-loaded cells showed sustained drug release over a 48 h period. Erythrocytes were loaded with PQ successfully, but there were some biochemical as well as physiological changes that resulted from the effect of PQ on the oxidative status of drug-loaded erythrocytes. These changes may result in favorable targeting of PQ-loaded cells to reticulo-endothelial organs. The relative impact of these changes remains to be explored in ongoing animal studies.

  16. Short GSM mobile phone exposure does not alter human auditory brainstem response

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    Thuróczy György

    2007-11-01

    Full Text Available Abstract Background There are about 1.6 billion GSM cellular phones in use throughout the world today. Numerous papers have reported various biological effects in humans exposed to electromagnetic fields emitted by mobile phones. The aim of the present study was to advance our understanding of potential adverse effects of the GSM mobile phones on the human hearing system. Methods Auditory Brainstem Response (ABR was recorded with three non-polarizing Ag-AgCl scalp electrodes in thirty young and healthy volunteers (age 18–26 years with normal hearing. ABR data were collected before, and immediately after a 10 minute exposure to 900 MHz pulsed electromagnetic field (EMF emitted by a commercial Nokia 6310 mobile phone. Fifteen subjects were exposed to genuine EMF and fifteen to sham EMF in a double blind and counterbalanced order. Possible effects of irradiation was analyzed by comparing the latency of ABR waves I, III and V before and after genuine/sham EMF exposure. Results Paired sample t-test was conducted for statistical analysis. Results revealed no significant differences in the latency of ABR waves I, III and V before and after 10 minutes of genuine/sham EMF exposure. Conclusion The present results suggest that, in our experimental conditions, a single 10 minute exposure of 900 MHz EMF emitted by a commercial mobile phone does not produce measurable immediate effects in the latency of auditory brainstem waves I, III and V.

  17. Insulin Is a Key Modulator of Fetoplacental Endothelium Metabolic Disturbances in Gestational Diabetes Mellitus

    Science.gov (United States)

    Sobrevia, Luis; Salsoso, Rocío; Fuenzalida, Bárbara; Barros, Eric; Toledo, Lilian; Silva, Luis; Pizarro, Carolina; Subiabre, Mario; Villalobos, Roberto; Araos, Joaquín; Toledo, Fernando; González, Marcelo; Gutiérrez, Jaime; Farías, Marcelo; Chiarello, Delia I.; Pardo, Fabián; Leiva, Andrea

    2016-01-01

    Gestational diabetes mellitus (GDM) is a disease of the mother that associates with altered fetoplacental vascular function. GDM-associated maternal hyperglycaemia result in fetal hyperglycaemia, a condition that leads to fetal hyperinsulinemia and altered L-arginine transport and synthesis of nitric oxide, i.e., endothelial dysfunction. These alterations in the fetoplacental endothelial function are present in women with GDM that were under diet or insulin therapy. Since these women and their newborn show normal glycaemia at term, other factors or conditions could be altered and/or not resolved by restoring normal level of circulating D-glucose. GDM associates with metabolic disturbances, such as abnormal handling of the locally released vasodilator adenosine, and biosynthesis and metabolism of cholesterol lipoproteins, or metabolic diseases resulting in endoplasmic reticulum stress and altered angiogenesis. Insulin acts as a potent modulator of all these phenomena under normal conditions as reported in primary cultures of cells obtained from the human placenta; however, GDM and the role of insulin regarding these alterations in this disease are poorly understood. This review focuses on the potential link between insulin and endoplasmic reticulum stress, hypercholesterolemia, and angiogenesis in GDM in the human fetoplacental vasculature. Based in reports in primary culture placental endothelium we propose that insulin is a factor restoring endothelial function in GDM by reversing ERS, hypercholesterolaemia and angiogenesis to a physiological state involving insulin activation of insulin receptor isoforms and adenosine receptors and metabolism in the human placenta from GDM pregnancies. PMID:27065887

  18. Insulin is a key modulator of fetoplacental endothelium metabolic disturbances in gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Luis eSobrevia

    2016-03-01

    Full Text Available Gestational diabetes mellitus (GDM is a disease of the mother that associates with altered fetoplacental vascular function. GDM–associated maternal hyperglycaemia result in fetal hyperglycaemia, a condition that leads to fetal hyperinsulinemia and altered L-arginine transport and synthesis of nitric oxide, i.e., endothelial dysfunction. These alterations in the fetoplacental endothelial function are present in women with GDM that were under diet or insulin therapy. Since these women and their newborn show normal glycaemia at term, other factors or conditions could be altered and/or not resolved by restoring a normal level of circulating D-glucose. GDM associates with metabolic disturbances, such as abnormal handling of the locally released vasodilator adenosine, and biosynthesis and metabolism of cholesterol lipoproteins, or metabolic diseases resulting in endoplasmic reticulum stress and altered angiogenesis. Insulin acts as a potent modulator of all these phenomena under normal conditions as reported in primary cultures of cells obtained from the human placenta; however, GDM and the role of insulin regarding these alterations in this disease are poorly understood. This review focuses on the potential link between insulin and endoplasmic reticulum stress, hypercholesterolemia, and angiogenesis in GDM in the human fetoplacental vasculature. Based in reports in primary culture placental endothelium we propose that insulin is a factor restoring endothelial function in GDM by reversing ERS, hypercholesterolaemia and angiogenesis to a physiological state involving insulin activation of insulin receptor isoforms and adenosine receptors and metabolism in the human placenta from GDM pregnancies.

  19. Human impacts on Caribbean coral reef ecosystems

    OpenAIRE

    Hardt, Marah Justine

    2007-01-01

    Fishing is one of the oldest anthropogenic disturbances in the ocean, differing from other impacts in its direct removal of biomass from the ecosystem. Despite the centuries of fishing activities, there is much we still do not understand regarding the effects of fish removal on the benthic community. I use an interdisciplinary approach to investigate the affect of human disturbance, primarily the alteration of fish communities, on major functional groups of coral reefs, over extended temporal...

  20. Recombinant Human Leptin Does Not Alter Gut Hormone Levels after Gastric Bypass but May Attenuate Sweet Cravings

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    Rushika Conroy

    2014-01-01

    Full Text Available Bariatric surgery improves glucose homeostasis and alters gut hormones partly independent of weight loss. Leptin plays a role in these processes; levels are decreased following bariatric surgery, creating a relative leptin insufficiency. We previously showed that leptin administration in a weight-reduced state after Roux-en-Y gastric bypass (RYGB caused no further weight loss. Here, we discuss the impact of leptin administration on gut hormones, glucostasis, and appetite. Weight stable women after RYGB were randomized to receive placebo or recombinant human metreleptin (0.05 mg/kg twice daily. At weeks 0 and 16, a liquid meal challenge was performed. Glucose, insulin, C-peptide, GLP-1, PYY, glucagon, and ghrelin (total, acyl, and desacyl were measured fasting and postprandially. Appetite was assessed using a visual analog scale. Mean post-op period was 53±2.3 months; mean BMI was 34.6±0.2 kg/m2. At 16 weeks, there was no significant change in weight within or between groups. Fasting PYY was significantly different between groups and the leptin group had lower sweets craving at week 16 than the placebo group (P<0.05. No other differences were observed. Leptin replacement does not alter gut hormones or glucostasis but may diminish sweet cravings compared to placebo in this population of post-RYGB women.

  1. Use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, J.D., E-mail: jennifer.cohen@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Babiarz, J.E., E-mail: joshua.babiarz@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Abrams, R.M., E-mail: rory.abrams@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Guo, L., E-mail: liang.guo@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Kameoka, S., E-mail: sei.kameoka@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Chiao, E., E-mail: eric.chiao@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Taunton, J., E-mail: taunton@cmp.ucsf.edu [Howard Hughes Medical Institute, Cellular and Molecular Pharmacology, University California San Francisco, San Francisco, CA 94158 (United States); Kolaja, K.L., E-mail: kyle.kolaja@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States)

    2011-11-15

    Sunitinib, an oral tyrosine kinase inhibitor approved to treat advanced renal cell carcinoma and gastrointestinal stroma tumor, is associated with clinical cardiac toxicity. Although the precise mechanism of sunitinib cardiotoxicity is not known, both the key metabolic energy regulator, AMP-activated protein kinase (AMPK), and ribosomal S 6 kinase (RSK) have been hypothesized as causative, albeit based on rodent models. To study the mechanism of sunitinib-mediated cardiotoxicity in a human model, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) having electrophysiological and contractile properties of native cardiac tissue were investigated. Sunitinib was cardiotoxic in a dose-dependent manner with an IC{sub 50} in the low micromolar range, observed by a loss of cellular ATP, an increase in oxidized glutathione, and induction of apoptosis in iPSC-CMs. Pretreatment of iPSC-CMs with AMPK activators AICAR or metformin, increased the phosphorylation of pAMPK-T172 and pACC-S79, but only marginally attenuated sunitinib mediated cell death. Furthermore, additional inhibitors of AMPK were not directly cytotoxic to iPSC-CMs up to 250 {mu}M concentrations. Inhibition of RSK with a highly specific, irreversible, small molecule inhibitor (RSK-FMK-MEA) did not induce cytotoxicity in iPSC-CMs below 250 {mu}M. Extensive electrophysiological analysis of sunitinib and RSK-FMK-MEA mediated conduction effects were performed. Taken together, these findings suggest that inhibition of AMPK and RSK are not a major component of sunitinib-induced cardiotoxicity. Although the exact mechanism of cardiotoxicity of sunitinib is not known, it is likely due to inhibition of multiple kinases simultaneously. These data highlight the utility of human iPSC-CMs in investigating the potential molecular mechanisms underlying drug-induced cardiotoxicity. -- Highlights: Black-Right-Pointing-Pointer Cytoxic effect of sunitinib on human stem cell derived cardiomyocytes Black

  2. TNF-α alters the inflammatory secretion profile of human first trimester placenta.

    Science.gov (United States)

    Siwetz, Monika; Blaschitz, Astrid; El-Heliebi, Amin; Hiden, Ursula; Desoye, Gernot; Huppertz, Berthold; Gauster, Martin

    2016-04-01

    Implantation and subsequent placental development depend on a well-orchestrated interaction between fetal and maternal tissues, involving a fine balanced synergistic cross-talk of inflammatory and immune-modulating factors. Tumor necrosis factor (TNF)-α has been increasingly recognized as pivotal factor for successful pregnancy, although high maternal TNF-α levels are associated with a number of adverse pregnancy conditions including gestational hypertension and gestational diabetes mellitus. This study describes effects of exogenously applied TNF-α, mimicking increased maternal TNF-α levels, on the secretion profile of inflammation associated factors in human first trimester villous placenta. Conditioned culture media from first trimester villous placental explants were analyzed by inflammation antibody arrays and ELISA after 48 h culture in the presence or absence of TNF-α. Inflammation antibody arrays identified interleukin (IL)-6, IL-8, chemokine (C-C motif) ligand 2 (CCL2), CCL4, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as the most abundantly secreted inflammation-associated factors under basal culture conditions. In the presence of TNF-α, secretion of GM-CSF, CCL5, and IL-10 increased, whereas IL-4 and macrophage CSF levels decreased compared with controls. ELISA analysis verified antibody arrays by showing significantly increased synthesis and release of GM-CSF and CCL5 by placental explants in response to TNF-α. Immunohistochemistry localized GM-CSF in the villous trophoblast compartment, whereas CCL5 was detected in maternal platelets adhering to perivillous fibrin deposits on the villous surface. mRNA-based in situ padlock probe approach localized GM-CSF and CCL5 transcripts in the villous trophoblast layer and the villous stroma. Results from this study suggest that the inflammatory secretion profile of human first trimester placenta shifts towards increased levels of GM-CSF, CCL5, and IL10 in response to elevated maternal

  3. Genistein inhibits invasive potential of human hepatocellular carcinoma by altering cell cycle, apoptosis, and angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Yan Gu; Chen-Fang Zhu; Hitoshi Iwamoto; Ji-Sheng Chen

    2005-01-01

    AIM: To study the in vitro and in vivo inhibitory effects of genistein on invasive potential of Bel 7402 hepatocellular carcinoma (HCC) cells and to explore the underlying mechanism.METHODS: Bel 7402 HCC cells were exposed to genistein. The invasive activity of tumor cells was assayed in transwell cell culture chamber. p125FAK expression and cell cycle were evaluated by a functional assay. Cell apoptosis analysis was performed with TUNEL method. In addition, bilateral subrenal capsule xenograft transplantation of HCC was performed in 10 nude mice.Genistein was injected and the invasion of HCC into the renal parenchyma was observed. Microvessels with immunohistochemical staining were detected.RESULTS: Genistein significantly inhibited the growth of Bel 7402 cells, the inhibitory rate of tumor cells was 26 -42%. The invasive potential of Bel 7402 cells in vitro was significantly inhibited, the inhibitory rate was 11-28%. Genistein caused G2/M cell cycle arrest, S phase decreased significantly. The occurrence of apoptosis in genistein group increased significantly. The expression of p125FAK in 5 μg/mL genistein group (15.26±0.16%)and 10 μg/mL genistein group (12.89±0.36%) was significantly lower than that in the control group (19.75± 1.12%,P<0.05). Tumor growth in genistein-treated nude mice was significantly retarded in comparison to control mice, the inhibitory rate of tumor growth was about 20%. Genistein also significantly inhibited the invasion of Bel 7402 cells into the renal parenchyma of nude mice with xenograft transplant. The positive unit value of microvessels in genistein-treated group (10.422±0.807)was significantly lower than that in control group (22.330 ± 5.696, P< 0.01).CONCLUSION: Genistein can effectively inhibit the invasive potential of Bel 7402 HCC cells by altering cell cycle, apoptosis and angiogenesis, inhibition of focal adhesion kinase may play a significant role in this process.

  4. Altered gravity modulates 5-lipoxygenase in human erythroleukemia K562 cells.

    Science.gov (United States)

    Maccarrone, M; Putti, S; Finazzi Agro, A

    1998-07-01

    Mammalian lipoxygenases catalyse the first committed step in the so-called "arachidonate cascade", leading to the production of potent bioactive molecules, such as leukotrienes, lipoxins and hepoxilins. Leukotrienes interact with G protein-couple receptors involved in neuronal plasticity and T lymphocyte activation, lipoxins activate leukocytes, hepoxilines control the insulin release and stimulate the phospholipase C. Lipoxygenase (linoleate:oxygen oxidoreductase; E.C. 1.13.11.34; 5-LOX) are responsible for lymphocyte maturation and programmed death (apoptosis) of neuronal cells. Therefore, 5-LOX might be Space relevant, because among the most striking effects of Space enviroment are indeed those on T lymphocyte activation, neuronal cell growth and suspectedly apoptosis. In this study, the possible effects of the force of gravity on the activity and expression of 5-LOX have been investigated by subjecting human erythroleukemia K562 cells to simulated hypogravity or hypergravity.

  5. Genome-wide transcriptomic alterations induced by ethanol treatment in human dental pulp stem cells (DPSCs

    Directory of Open Access Journals (Sweden)

    Omar Khalid

    2014-12-01

    Full Text Available Human dental pulp stem cells (DPSCs isolated from adult dental pulp are multipotent mesenchymal stem cells that can be directed to differentiate into osteogenic/odontogenic cells and also trans-differentiate into neuronal cells. The utility of DPSC has been explored in odontogenic differentiation for tooth regeneration. Alcohol abuse appears to lead to periodontal disease, tooth decay and mouth sores that are potentially precancerous. Persons who abuse alcohol are at high risk of having seriously deteriorated teeth, gums and compromised oral health in general. It is currently unknown if alcohol exposure has any impact on adult stem cell maintenance, stem cell fate determination and plasticity, and stem cell niche environment. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO under GSE57255. Our data provide transcriptomic changes that are occurring by EtOH treatment of DPSCs at 24-hour and 48-hour time point.

  6. Exposure to Music Alters Cell Viability and Cell Motility of Human Nonauditory Cells in Culture

    Directory of Open Access Journals (Sweden)

    Nathalia R. Lestard

    2016-01-01

    Full Text Available Although music is part of virtually all cultures in the world, little is known about how it affects us. Since the beginning of this century several studies suggested that the response to music, and to sound in general, is complex and might not be exclusively due to emotion, given that cell types other than auditory hair cells can also directly react to audible sound. The present study was designed to better understand the direct effects of acoustic vibrations, in the form of music, in human cells in culture. Our results suggest that the mechanisms of cell growth arrest and/or cell death induced by acoustic vibrations are similar for auditory and nonauditory cells.

  7. Amphetamine Sensitization Alters Reward Processing in the Human Striatum and Amygdala

    Science.gov (United States)

    O’Daly, Owen G.; Joyce, Daniel; Tracy, Derek K.; Azim, Adnan; Stephan, Klaas E.; Murray, Robin M.; Shergill, Sukhwinder S.

    2014-01-01

    Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS) has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD) signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders. PMID:24717936

  8. Amphetamine sensitization alters reward processing in the human striatum and amygdala.

    Directory of Open Access Journals (Sweden)

    Owen G O'Daly

    Full Text Available Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.

  9. Short-term high dose of quercetin and resveratrol alters aging markers in human kidney cells

    Directory of Open Access Journals (Sweden)

    Fatemeh Abharzanjani

    2017-01-01

    Full Text Available Background: Hyperglycemia-mediated oxidative stress implicates in etiology of kidney cell aging and diabetic nephropathy. We evaluated the effects of different doses of resveratrol and quercetin and their combination therapy on aging marker in human kidney cell culture under hyperglycemia condition. Methods: Human embryonic kidney cell (HEK-293 was cultured in Dulbecco's Modified Eagle Medium (DMEM containing 100 mM (18 mg/L for 24 h. The cells were treated with resveratrol (2.5, 5, 10 μm, quercetin (3, 6, 12 μm, and combination of these (R 2.5 μm, Q 3 μm and (R 5 μm, Q 6 μm and (R 10 μm, Q 12 μm for 48 h, and then, cells were lysed to access RNA and lysate. Results: The analysis of data showed that beta-galactosidase enzyme gene expression as an aging marker in all treatment groups has reduced in a dose-dependent manner. Gene expression of Sirtuin1 and thioredoxin (Trx in all treated groups in comparison to control group increased in a dose-dependent fashion. Trx interacting protein (TXNIP gene expression decreased in a dose-dependent manner in all treated groups, especially in resveratrol and combination therapy. Conclusions: According to the results of this research, quercetin, resveratrol, and especially combination treatments with increased expression levels of antioxidants, can reduce aging markers in HEK cell line in hyperglycemia conditions. These results lead us to use flavonoids such as resveratrol for anti-aging potential.

  10. Combined facial heating and inhalation of hot air do not alter thermoeffector responses in humans.

    Science.gov (United States)

    Wingo, Jonathan E; Low, David A; Keller, David M; Kimura, Kenichi; Crandall, Craig G

    2015-09-01

    The influence of thermoreceptors in human facial skin on thermoeffector responses is equivocal; furthermore, the presence of thermoreceptors in the respiratory tract and their involvement in thermal homeostasis has not been elucidated. This study tested the hypothesis that hot air directed on the face and inhaled during whole body passive heat stress elicits an earlier onset and greater sensitivity of cutaneous vasodilation and sweating than that directed on an equal skin surface area away from the face. Six men and two women completed two trials separated by ∼1 wk. Part