Exposure Through Runoff and Ground Water Contamination Differentially Impact Behavior and Physiology of Crustaceans in Fluvial Systems.

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Steele, Alexandra N; Belanger, Rachelle M; Moore, Paul A

2018-06-19

Chemical pollutants enter aquatic systems through numerous pathways (e.g., surface runoff and ground water contamination), thus associating these contaminant sources with varying hydrodynamic environments. The hydrodynamic environment shapes the temporal and spatial distribution of chemical contaminants through turbulent mixing. The differential dispersal of contaminants is not commonly addressed in ecotoxicological studies and may have varying implications for organism health. The purpose of this study is to understand how differing routes of exposure to atrazine alter social behaviors and physiological responses of aquatic organisms. This study used agonistic encounters in crayfish Orconectes virilis as a behavioral assay to investigate impact of sublethal concentrations of atrazine (0, 40, 80, and 160 µg/L) delivered by methods mimicking ground water and surface runoff influx into flow-through exposure arenas for a total of 23 h. Each experimental animal participated in a dyadic fight trial with an unexposed opponent. Fight duration and intensity were analyzed. Experimental crayfish hepatopancreas and abdominal muscle tissue samples were analyzed for cytochrome P450 and acetylcholinesterase levels to discern mechanism of detoxification and mode of action of atrazine. Atrazine delivered via runoff decreased crayfish overall fight intensity and contrastingly ground water delivery increased overall fight intensity. The behavioral differences were mirrored by increases in cytochrome P450 activity, whereas no differences were found in acetylcholinesterase activity. This study demonstrates that method of delivery into fluvial systems has differential effects on both behavior and physiology of organisms and emphasizes the need for the consideration of delivery pathway in ecotoxicological studies and water-impairment standards.

Differential response of olfactory sensory neuron populations to copper ion exposure in zebrafish

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Lazzari, Maurizio, E-mail: maurizio.lazzari@unibo.it; Bettini, Simone; Milani, Liliana; Maurizii, Maria Gabriella; Franceschini, Valeria

2017-02-15

Highlights: • Copper exposure affects ciliated olfactory receptors more than microvillar cells. • Crypt olfactory sensory neurons are not affected by copper exposure. • Copper exposure induces an increase in the amount of sensory epithelium. - Abstract: The peripheral olfactory system of fish is in direct contact with the external aqueous environment, so dissolved contaminants can easily impair sensory functions and cause neurobehavioral injuries. The olfactory epithelium of fish is arranged in lamellae forming a rosette in the olfactory cavity and contains three main types of olfactory sensory neurons (OSNs): ciliated (cOSNs) and microvillous olfactory sensory neurons (mOSNs), common to all vertebrates, and a third minor group of olfactory neurons, crypt cells, absent in tetrapods. Since copper is a ubiquitously diffusing olfactory toxicant and a spreading contaminant in urban runoff, we investigated the effect of low copper concentration on the three different OSNs in the olfactory epithelium of zebrafish, a model system widely used in biological research. Image analysis was applied for morphometry and quantification of immunohistochemically detected OSNs. Copper exposure resulted in an evident decrease in olfactory epithelium thickness. Moreover, after exposure, the lamellae of the dorsal and ventral halves of the olfactory rosettes showed a different increase in their sensory areas, suggesting a lateral migration of new cells into non-sensory regions. The results of the present study provide clear evidence of a differential response of the three neural cell populations of zebrafish olfactory mucosa after 96 h of exposure to copper ions at the sublethal concentration of 30 μg L{sup −1}. Densitometric values of cONS, immunostained with anti-G {sub αolf}, decreased of about 60% compared to the control. When the fish were transferred to water without copper addition and examined after 3, 10 and 30 days, we observed a partial restoration of anti-G {sub �

Differential response of olfactory sensory neuron populations to copper ion exposure in zebrafish

International Nuclear Information System (INIS)

Lazzari, Maurizio; Bettini, Simone; Milani, Liliana; Maurizii, Maria Gabriella; Franceschini, Valeria

2017-01-01

Highlights: • Copper exposure affects ciliated olfactory receptors more than microvillar cells. • Crypt olfactory sensory neurons are not affected by copper exposure. • Copper exposure induces an increase in the amount of sensory epithelium. - Abstract: The peripheral olfactory system of fish is in direct contact with the external aqueous environment, so dissolved contaminants can easily impair sensory functions and cause neurobehavioral injuries. The olfactory epithelium of fish is arranged in lamellae forming a rosette in the olfactory cavity and contains three main types of olfactory sensory neurons (OSNs): ciliated (cOSNs) and microvillous olfactory sensory neurons (mOSNs), common to all vertebrates, and a third minor group of olfactory neurons, crypt cells, absent in tetrapods. Since copper is a ubiquitously diffusing olfactory toxicant and a spreading contaminant in urban runoff, we investigated the effect of low copper concentration on the three different OSNs in the olfactory epithelium of zebrafish, a model system widely used in biological research. Image analysis was applied for morphometry and quantification of immunohistochemically detected OSNs. Copper exposure resulted in an evident decrease in olfactory epithelium thickness. Moreover, after exposure, the lamellae of the dorsal and ventral halves of the olfactory rosettes showed a different increase in their sensory areas, suggesting a lateral migration of new cells into non-sensory regions. The results of the present study provide clear evidence of a differential response of the three neural cell populations of zebrafish olfactory mucosa after 96 h of exposure to copper ions at the sublethal concentration of 30 μg L"−"1. Densitometric values of cONS, immunostained with anti-G _α_o_l_f, decreased of about 60% compared to the control. When the fish were transferred to water without copper addition and examined after 3, 10 and 30 days, we observed a partial restoration of anti-G _�

Differential Exposure to Hazardous Air Pollution in the United States: A Multilevel Analysis of Urbanization and Neighborhood Socioeconomic Deprivation

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Frank C. Curriero

2012-06-01

Full Text Available Population exposure to multiple chemicals in air presents significant challenges for environmental public health. Air quality regulations distinguish criteria air pollutants (CAPs (e.g., ozone, PM2.5 from hazardous air pollutants (HAPs—187 chemicals which include carcinogens and others that are associated with respiratory, cardiovascular, neurological and numerous other non-cancer health effects. Evidence of the public’s cumulative exposure and the health effects of HAPs are quite limited. A multilevel model is used to assess differential exposure to HAP respiratory, neurological, and cancer hazards (2005 related to the Townsend Index of Socioeconomic Deprivation (TSI, after adjustment for regional population size and economic activity, and local population density. We found significant positive associations between tract TSI and respiratory and cancer HAP exposure hazards, and smaller effects for neurological HAPs. Tracts in the top quintile of TSI have between 38%–60% higher HAP exposure than the bottom quintile; increasing population size from the bottom quintile to the top quintile modifies HAP exposure hazard related to TSI, increasing cancer HAP exposure hazard by 6% to 20% and increasing respiratory HAP exposure hazard by 12% to 27%. This study demonstrates the value of social epidemiological methods for analyzing differential exposure and advancing cumulative risk assessment.

Differential exposure to hazardous air pollution in the United States: a multilevel analysis of urbanization and neighborhood socioeconomic deprivation.

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Young, Gary S; Fox, Mary A; Trush, Michael; Kanarek, Norma; Glass, Thomas A; Curriero, Frank C

2012-06-01

Population exposure to multiple chemicals in air presents significant challenges for environmental public health. Air quality regulations distinguish criteria air pollutants (CAPs) (e.g., ozone, PM2.5) from hazardous air pollutants (HAPs)-187 chemicals which include carcinogens and others that are associated with respiratory, cardiovascular, neurological and numerous other non-cancer health effects. Evidence of the public's cumulative exposure and the health effects of HAPs are quite limited. A multilevel model is used to assess differential exposure to HAP respiratory, neurological, and cancer hazards (2005) related to the Townsend Index of Socioeconomic Deprivation (TSI), after adjustment for regional population size and economic activity, and local population density. We found significant positive associations between tract TSI and respiratory and cancer HAP exposure hazards, and smaller effects for neurological HAPs. Tracts in the top quintile of TSI have between 38%-60% higher HAP exposure than the bottom quintile; increasing population size from the bottom quintile to the top quintile modifies HAP exposure hazard related to TSI, increasing cancer HAP exposure hazard by 6% to 20% and increasing respiratory HAP exposure hazard by 12% to 27%. This study demonstrates the value of social epidemiological methods for analyzing differential exposure and advancing cumulative risk assessment.

Effects of radiofrequency exposure emitted from a GSM mobile phone on proliferation, differentiation, and apoptosis of neural stem cells

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Eghlidospour, Mahsa; Ghanbari, Amir

2017-01-01

Due to the importance of neural stem cells (NSCs) in plasticity of the nervous system and treating neurodegenerative diseases, the main goal of this study was to evaluate the effects of radiofrequency radiation emitted from a GSM 900-MHz mobile phone with different exposure duration on proliferation, differentiation and apoptosis of adult murine NSCs in vitro. We used neurosphere assay to evaluate NSCs proliferation, and immunofluorescence assay of neural cell markers to examine NSCs differentiation. We also employed alamarBlue and caspase 3 apoptosis assays to assess harmful effects of mobile phone on NSCs. Our results showed that the number and size of resulting neurospheres and also the percentage of cells differentiated into neurons decreased significantly with increasing exposure duration to GSM 900-MHz radiofrequency (RF)-electromagnetic field (EMF). In contrast, exposure to GSM 900-MHz RF-EMF at different durations did not influence cell viability and apoptosis of NSCs and also their astrocytic differentiation. It is concluded that accumulating dose of GSM 900-MHz RF-EMF might have devastating effects on NSCs proliferation and neurogenesis requiring more causations in terms of using mobile devices. PMID:28713615

Transient Exposure to Ethanol during Zebrafish Embryogenesis Results in Defects in Neuronal Differentiation: An Alternative Model System to Study FASD

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Joya, Xavier; Garcia-Algar, Oscar; Vall, Oriol; Pujades, Cristina

2014-01-01

Background The exposure of the human embryo to ethanol results in a spectrum of disorders involving multiple organ systems, including the impairment of the development of the central nervous system (CNS). In spite of the importance for human health, the molecular basis of prenatal ethanol exposure remains poorly understood, mainly to the difficulty of sample collection. Zebrafish is now emerging as a powerful organism for the modeling and the study of human diseases. In this work, we have assessed the sensitivity of specific subsets of neurons to ethanol exposure during embryogenesis and we have visualized the sensitive embryonic developmental periods for specific neuronal groups by the use of different transgenic zebrafish lines. Methodology/Principal Findings In order to evaluate the teratogenic effects of acute ethanol exposure, we exposed zebrafish embryos to ethanol in a given time window and analyzed the effects in neurogenesis, neuronal differentiation and brain patterning. Zebrafish larvae exposed to ethanol displayed small eyes and/or a reduction of the body length, phenotypical features similar to the observed in children with prenatal exposure to ethanol. When neuronal populations were analyzed, we observed a clear reduction in the number of differentiated neurons in the spinal cord upon ethanol exposure. There was a decrease in the population of sensory neurons mainly due to a decrease in cell proliferation and subsequent apoptosis during neuronal differentiation, with no effect in motoneuron specification. Conclusion Our investigation highlights that transient exposure to ethanol during early embryonic development affects neuronal differentiation although does not result in defects in early neurogenesis. These results establish the use of zebrafish embryos as an alternative research model to elucidate the molecular mechanism(s) of ethanol-induced developmental toxicity at very early stages of embryonic development. PMID:25383948

Transient exposure to ethanol during zebrafish embryogenesis results in defects in neuronal differentiation: an alternative model system to study FASD.

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Xavier Joya

Full Text Available The exposure of the human embryo to ethanol results in a spectrum of disorders involving multiple organ systems, including the impairment of the development of the central nervous system (CNS. In spite of the importance for human health, the molecular basis of prenatal ethanol exposure remains poorly understood, mainly to the difficulty of sample collection. Zebrafish is now emerging as a powerful organism for the modeling and the study of human diseases. In this work, we have assessed the sensitivity of specific subsets of neurons to ethanol exposure during embryogenesis and we have visualized the sensitive embryonic developmental periods for specific neuronal groups by the use of different transgenic zebrafish lines.In order to evaluate the teratogenic effects of acute ethanol exposure, we exposed zebrafish embryos to ethanol in a given time window and analyzed the effects in neurogenesis, neuronal differentiation and brain patterning. Zebrafish larvae exposed to ethanol displayed small eyes and/or a reduction of the body length, phenotypical features similar to the observed in children with prenatal exposure to ethanol. When neuronal populations were analyzed, we observed a clear reduction in the number of differentiated neurons in the spinal cord upon ethanol exposure. There was a decrease in the population of sensory neurons mainly due to a decrease in cell proliferation and subsequent apoptosis during neuronal differentiation, with no effect in motoneuron specification.Our investigation highlights that transient exposure to ethanol during early embryonic development affects neuronal differentiation although does not result in defects in early neurogenesis. These results establish the use of zebrafish embryos as an alternative research model to elucidate the molecular mechanism(s of ethanol-induced developmental toxicity at very early stages of embryonic development.

Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In Vitro and its Perturbation by Low-Dose Bisphenol A Exposure.

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Esther L Calderon-Gierszal

Full Text Available Studies using rodent and adult human prostate stem-progenitor cell models suggest that developmental exposure to the endocrine disruptor Bisphenol-A (BPA can predispose to prostate carcinogenesis with aging. Unknown at present is whether the embryonic human prostate is equally susceptible to BPA during its natural developmental window. To address this unmet need, we herein report the construction of a pioneer in vitro human prostate developmental model to study the effects of BPA. The directed differentiation of human embryonic stem cells (hESC into prostatic organoids in a spatial system was accomplished with precise temporal control of growth factors and steroids. Activin-induced definitive endoderm was driven to prostate specification by combined exposure to WNT10B and FGF10. Matrigel culture for 20-30 days in medium containing R-Spondin-1, Noggin, EGF, retinoic acid and testosterone was sufficient for mature prostate organoid development. Immunofluorescence and gene expression analysis confirmed that organoids exhibited cytodifferentiation and functional properties of the human prostate. Exposure to 1 nM or 10 nM BPA throughout differentiation culture disturbed early morphogenesis in a dose-dependent manner with 1 nM BPA increasing and 10 nM BPA reducing the number of branched structures formed. While differentiation of branched structures to mature organoids seemed largely unaffected by BPA exposure, the stem-like cell population increased, appearing as focal stem cell nests that have not properly entered lineage commitment rather than the rare isolated stem cells found in normally differentiated structures. These findings provide the first direct evidence that low-dose BPA exposure targets hESC and perturbs morphogenesis as the embryonic cells differentiate towards human prostate organoids, suggesting that the developing human prostate may be susceptible to disruption by in utero BPA exposures.

Assessment of health risks from exposure to ionizing radiation

International Nuclear Information System (INIS)

Beebe, G.W.

1982-01-01

Rapid development in the assessment of health risks from exposure to ionizing radiation has produced an impressive array of risk differentials of presumed biologic significance. In the human data these differentials involve: (1) the variety of cancer, especially its size; (2) host factors, especially age; (3) time following exposure; (4) magnitude of dose; and (5) type of radiation. From experimental work we may presume that dose-rate also plays a role, especially for sparsely ionizing radiation. Current research is extending the scope of differentials with respect to these and other variables, including cell type and concomitant environmental risk factors, and testing dose-response models suggested by experimental and theoretical work. As facts to be explained, differentials in risk may lead to hypotheses to be explored experimentally and improve our understanding of how ionizing radiation causes cancer. 74 references

Microarray applications to understand the impact of exposure to environmental contaminants in wild dolphins (Tursiops truncatus).

Science.gov (United States)

Mancia, Annalaura; Abelli, Luigi; Kucklick, John R; Rowles, Teresa K; Wells, Randall S; Balmer, Brian C; Hohn, Aleta A; Baatz, John E; Ryan, James C

2015-02-01

It is increasingly common to monitor the marine environment and establish geographic trends of environmental contamination by measuring contaminant levels in animals from higher trophic levels. The health of an ecosystem is largely reflected in the health of its inhabitants. As an apex predator, the common bottlenose dolphin (Tursiops truncatus) can reflect the health of near shore marine ecosystems, and reflect coastal threats that pose risk to human health, such as legacy contaminants or marine toxins, e.g. polychlorinated biphenyls (PCBs) and brevetoxins. Major advances in the understanding of dolphin biology and the unique adaptations of these animals in response to the marine environment are being made as a result of the development of cell-lines for use in in vitro experiments, the production of monoclonal antibodies to recognize dolphin proteins, the development of dolphin DNA microarrays to measure global gene expression and the sequencing of the dolphin genome. These advances may play a central role in understanding the complex and specialized biology of the dolphin with regard to how this species responds to an array of environmental insults. This work presents the creation, characterization and application of a new molecular tool to better understand the complex and unique biology of the common bottlenose dolphin and its response to environmental stress and infection. A dolphin oligo microarray representing 24,418 unigene sequences was developed and used to analyze blood samples collected from 69 dolphins during capture-release health assessments at five geographic locations (Beaufort, NC, Sarasota Bay, FL, Saint Joseph Bay, FL, Sapelo Island, GA and Brunswick, GA). The microarray was validated and tested for its ability to: 1) distinguish male from female dolphins; 2) differentiate dolphins inhabiting different geographic locations (Atlantic coasts vs the Gulf of Mexico); and 3) study in detail dolphins resident in one site, the Georgia coast, known to

Differential effect of exposure-based therapy and cognitive therapy on post-traumatic stress disorder symptom clusters: A randomized controlled trial.

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Horesh, Danny; Qian, Meng; Freedman, Sara; Shalev, Arieh

2017-06-01

A question remains regarding differential effects of exposure-based versus non-exposure-based therapies on specific post-traumatic stress disorder (PTSD) symptom clusters. Traumatized emergency room patients were randomized to receive prolonged exposure (PE) or cognitive therapy (CT) without exposure. PE/CT had no differential effect on individual symptom clusters, and change in total PTSD score remained significant even after controlling for the reductions in all three symptom clusters. In addition, baseline levels of PTSD avoidance/intrusion/hyperarousal did not moderate the effects of PE and CT on total PTSD symptom scores. Taken together, these findings challenge the notion that PE and CT are specifically, and differentially, useful in treating one particular PTSD symptom cluster. Despite their different theoretical backgrounds and techniques, the notion that PE and CT (without exposure) target different PTSD symptoms was not confirmed in this study. Thus, both interventions may in fact be equally effective for treating intrusion, avoidance and hyperarousal symptoms. Baseline levels of avoidance, intrusion and hyperarousal may not be good a priori indicators for PTSD treatment selection. The effect of PE and CT on PTSD as a whole does not seem to depend on a reduction in any specific symptom cluster. These findings indicate that exposure and non-exposure interventions may lead to similar results in terms of reductions in specific PTSD symptoms. It is quite possible that individual PTSD clusters may respond to therapy in an inter-related fashion, with one cluster affecting the other. © 2016 The British Psychological Society.

Prospective risk factors for adolescent PTSD: sources of differential exposure and differential vulnerability.

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Milan, Stephanie; Zona, Kate; Acker, Jenna; Turcios-Cotto, Viana

2013-02-01

There are two types of risk factors for developing PTSD: factors that increase the likelihood of experiencing a potentially traumatizing event and factors that increase the likelihood of developing symptoms following such events. Using prospective data over a two-year period from a large, diverse sample of urban adolescents (n = 1242, Mean age = 13.5), the current study differentiates these two sources of risk for developing PTSD in response to violence exposure. Five domains of potential risk and protective factors were examined: community context (e.g., neighborhood poverty), family risk (e.g., family conflict), behavioral maladjustment (e.g., internalizing symptoms), cognitive vulnerabilities (e.g., low IQ), and interpersonal problems (e.g., low social support). Time 1 interpersonal violence history, externalizing behaviors, and association with deviant peers were the best predictors of subsequent violence, but did not further increase the likelihood of PTSD in response to violence. Race/ethnicity, thought disorder symptoms, and social problems were distinctly predictive of the development of PTSD following violence exposure. Among youth exposed to violence, Time 1 risk factors did not predict specific event features associated with elevated PTSD rates (e.g., parent as perpetrator), nor did interactions between Time 1 factors and event features add significantly to the prediction of PTSD diagnosis. Findings highlight areas for refinement in adolescent PTSD symptom measures and conceptualization, and provide direction for more targeted prevention and intervention efforts.

Increasing the understanding of chemical concepts: The effectiveness of multiple exposures

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Bius, Janet H.

Chemistry is difficult because it has multilevels of knowledge with each level presenting challenges in vocabulary, abstract thinking, and symbolic language. Students have to be able to transfer between levels to understand the concepts and the theoretical models of chemistry. The cognitive theories of constructivism and cognitive-load theory are used to explain the difficulties novice learners have with the subject of chemistry and methods to increase success for students. The relationship between external representations, misconceptions and topics on the success of students are addressed. If students do not know the formalisms associated with chemical diagrams and graphs, the representations will decrease student success. Misconceptions can be formed when new information is interpreted based on pre-existing knowledge that is faulty. Topics with large amount of interacting elements that must be processed simultaneously are considered difficult to understand. New variables were created to measure the number of times a student is exposed to a chemical concept. Each variable was coded according to topic and learning environment, which are the lecture and laboratory components of the course, homework assignments and textbook examples. The exposure variables are used to measure the success rate of students on similar exam questions. Question difficulty scales were adapted for this project from those found in the chemical education literature. The exposure variables were tested on each level of the difficulty scales to determine their effect at decreasing the cognitive demand of these questions. The subjects of this study were freshmen science majors at a large Midwest university. The effects of the difficulty scales and exposure variables were measured for those students whose exam scores were in the upper one-fourth percentile, for students whose test scores were in the middle one-half percentile, and the lower one-fourth percentile are those students that scored the

Effects of in ovo exposure of Imazalil and Atrazine on sexual differentiation in chick gonads

Energy Technology Data Exchange (ETDEWEB)

Yamashita, J.; Ikeda, M. [Univ. of Shizuoka, Shizuoka (Japan); Matsushita, S.; Iwasawa, T.; Ikeya, M. [Shizuoka Swine and Poultry Experiment Station, Kikugawa (Japan)

2004-09-15

numerous anti-fungal chemicals. These chemicals have shown to reversibly (although not necessarily competitively) inhibit aromatase activity in human placental microsomes. It is reported that imazalil and difenoconazole inhibit aromatase activity in human adrenocortical carcinoma cell line H295R. Atrazine is the most commonly used herbicide in the word. There are several reports about the adverse effects of atrazine exposure. Atrazine induced hermaphroditism in African clawed frogs and demasculinized the larynx in male frogs. Plasma testosterone concentration in male frogs was decreased by atrazine exposure, and plasma estradiol concentration in rats was increased by atrazine exposure. Atrazine also increased aromatase activity in human adrenocortical carcinoma cell line H295R by inducing aromatase mRNA. In this study, the effects of in ovo exposure to an aromatase-inhibiting chemical (imazalil) and an aromatase-activating chemical (atrazine) on the sexual differentiation of chick gonad were investigated.

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

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Nazia Chaudhuri

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

Differential protein expression of hepatic cells associated with MeHg exposure: deepening into the molecular mechanisms of toxicity

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Cuello, Susana; Madrid, Yolanda; Luque-Garcia, Jose L.; Camara, Carmen [Complutense University of Madrid, Department of Analytical Chemistry, Faculty of Chemistry, Madrid (Spain); Ramos, Sonia [Institute of Food Science, Technology and Nutrition, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid (Spain)

2012-08-15

Understanding the molecular mechanisms underlying MeHg toxicity and the way in which this molecule interacts with living organisms is a critical point since MeHg represents a well-known risk to ecosystems and human health. We used a quantitative proteomic approach based on stable isotopic labeling by amino acids in cell culture in combination with SDS-PAGE and nanoflow LC-ESI-LTQ for analyzing the differential protein expression of hepatic cells associated to MeHg exposure. Seventy-eight proteins were found de-regulated by more than 1.5-fold. We identified a number of proteins involved in different essential biological processes including apoptosis, mitochondrial dysfunction, cellular trafficking and energy production. Among these proteins, we found several molecules whose de-regulation has been already related to MeHg exposure, thus confirming the usefulness of our discovery approach, and new ones that helped to gain a deeper insight into the biomolecular mechanisms related to MeHg-induced toxicity. Overexpression of several HSPs and the proteasome 26S subunit itself showed the proteasome system as a molecular target of toxic MeHg. As for the interaction networks, the top ranked was the nucleic acid metabolism, where many of the identified de-regulated proteins are involved. (orig.)

Diclofenac and triamcinolone acetonide impair tenocytic differentiation and promote adipocytic differentiation of mesenchymal stem cells.

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Fredriksson, Maritha; Li, Yan; Stålman, Anders; Haldosén, Lars-Arne; Felländer-Tsai, Li

2013-09-02

Tendinopathies are often empirically treated with oral/topical nonsteroidal anti-inflammatory medications and corticosteroid injections despite their unclear effects on tendon regeneration. Recent studies indicate that tendon progenitors exhibit stem cell-like properties, i.e., differentiation to osteoblasts, adipocytes, and chondrocytes, in addition to tenocytes. Our present study aims at understanding the effects of triamcinolone acetonide and diclofenac on tenocytic differentiation of mesenchymal stem cells. The murine fibroblast C3H10T1/2 cell line was induced to tenocytic differentiation by growth differentiation factor-7. Cell proliferation and differentiation with the exposure of different concentrations of triamcinolone acetonide and diclofenac were measured by WST-1 assay and real-time polymerase chain reaction analysis, respectively. Cell proliferation was decreased in a concentration-dependent manner when exposed to triamcinolone acetonide and diclofenac. In addition to tenocytic differentiation, adipocyte formation was observed, both at gene expression and microscopic level, when the cells were exposed to triamcinolone acetonide or high concentrations of diclofenac. Our results indicate that triamcinolone acetonide and diclofenac might alter mesenchymal stem cell differentiation in a nonfavorable way regarding tendon regeneration; therefore, these medications should be used with more caution clinically.

Detection of Radiation-Exposure Biomarkers by Differential Mobility Prefiltered Mass Spectrometry (DMS-MS).

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Coy, Stephen L; Krylov, Evgeny V; Schneider, Bradley B; Covey, Thomas R; Brenner, David J; Tyburski, John B; Patterson, Andrew D; Krausz, Kris W; Fornace, Albert J; Nazarov, Erkinjon G

2010-04-15

Technology to enable rapid screening for radiation exposure has been identified as an important need, and, as a part of a NIH / NIAD effort in this direction, metabolomic biomarkers for radiation exposure have been identified in a recent series of papers. To reduce the time necessary to detect and measure these biomarkers, differential mobility spectrometry - mass spectrometry (DMS-MS) systems have been developed and tested. Differential mobility ion filters preselect specific ions and also suppress chemical noise created in typical atmospheric-pressure ionization sources (ESI, MALDI, and others). Differential-mobility-based ion selection is based on the field dependence of ion mobility, which, in turn, depends on ion characteristics that include conformation, charge distribution, molecular polarizability, and other properties, and on the transport gas composition which can be modified to enhance resolution. DMS-MS is able to resolve small-molecule biomarkers from nearly-isobaric interferences, and suppresses chemical noise generated in the ion source and in the mass spectrometer, improving selectivity and quantitative accuracy. Our planar DMS design is rapid, operating in a few milliseconds, and analyzes ions before fragmentation. Depending on MS inlet conditions, DMS-selected ions can be dissociated in the MS inlet expansion, before mass analysis, providing a capability similar to MS/MS with simpler instrumentation. This report presents selected DMS-MS experimental results, including resolution of complex test mixtures of isobaric compounds, separation of charge states, separation of isobaric biomarkers (citrate and isocitrate), and separation of nearly-isobaric biomarker anions in direct analysis of a bio-fluid sample from the radiation-treated group of a mouse-model study. These uses of DMS combined with moderate resolution MS instrumentation indicate the feasibility of field-deployable instrumentation for biomarker evaluation.

Developmental exposure to bisphenol A (BPA) alters sexual differentiation in painted turtles (Chrysemys picta)

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Jandegian, Caitlin M.; Deem, Sharon L.; Bhandari, Ramji K.; Holliday, Casey M.; Nicks, Diane; Rosenfeld, Cheryl S.; Selcer, Kyle; Tillitt, Donald E.; vom Saal, Fredrick S.; Velez, Vanessa; Yang, Ying; Holliday, Dawn K.

2015-01-01

Environmental chemicals can disrupt endocrine signaling and adversely impact sexual differentiation in wildlife. Bisphenol A (BPA) is an estrogenic chemical commonly found in a variety of habitats. In this study, we used painted turtles (Chrysemys picta), which have temperature-dependent sex determination (TSD), as an animal model for ontogenetic endocrine disruption by BPA. We hypothesized that BPA would override TSD and disrupt sexual development. We incubated farm-raised turtle eggs at the male-producing temperature (26 °C), randomly assigned individuals to treatment groups: control, vehicle control, 17β-estradiol (E2, 20 ng/g-egg) or 0.01, 1.0, 100 μg BPA/g-egg and harvested tissues at hatch. Typical female gonads were present in 89% of the E2-treated “males”, but in none of the control males (n = 35). Gonads of BPA-exposed turtles had varying amounts of ovarian-like cortical (OLC) tissue and disorganized testicular tubules in the medulla. Although the percentage of males with OLCs increased with BPA dose (BPA-low = 30%, BPA-medium = 33%, BPA-high = 39%), this difference was not significant (p = 0.85). In all three BPA treatments, SOX9 patterns revealed disorganized medullary testicular tubules and β-catenin expression in a thickened cortex. Liver vitellogenin, a female-specific liver protein commonly used as an exposure biomarker, was not induced by any of the treatments. Notably, these results suggest that developmental exposure to BPA disrupts sexual differentiation in painted turtles. Further examination is necessary to determine the underlying mechanisms of sex reversal in reptiles and how these translate to EDC exposure in wild populations.

Time series models of environmental exposures: Good predictions or good understanding.

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Barnett, Adrian G; Stephen, Dimity; Huang, Cunrui; Wolkewitz, Martin

2017-04-01

Time series data are popular in environmental epidemiology as they make use of the natural experiment of how changes in exposure over time might impact on disease. Many published time series papers have used parameter-heavy models that fully explained the second order patterns in disease to give residuals that have no short-term autocorrelation or seasonality. This is often achieved by including predictors of past disease counts (autoregression) or seasonal splines with many degrees of freedom. These approaches give great residuals, but add little to our understanding of cause and effect. We argue that modelling approaches should rely more on good epidemiology and less on statistical tests. This includes thinking about causal pathways, making potential confounders explicit, fitting a limited number of models, and not over-fitting at the cost of under-estimating the true association between exposure and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of electronic tongue for differentiation of tomato taste by cultivar, harvest maturity, and chilling or heating exposure

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The objective of this research was to evaluate whether an electronic-tongue (etongue) could differentiate “taste” profiles of tomato fruit between different cultivars, harvest maturities, and postharvest chilling or heating exposure. The four cultivars included: two common commercial cultivars, ‘Tyg...

Differential environmental exposure among non-Indigenous Canadians as a function of sex/gender and race/ethnicity variables: a scoping review.

Science.gov (United States)

Chakravartty, Dolon; Wiseman, Clare L S; Cole, Donald C

2014-11-21

To determine the extent, range and types of studies of differential environmental chemical exposures among non-Indigenous Canadians as a function of sex/gender and race/ethnicity. Computerized database searches were performed from November to December 2013 using Medline, Embase, CAB Abstracts, Proquest and Scopus to identify relevant studies of environmental exposures among non-Indigenous adults aged ≥18 years in Canada published between 1993 and 2013. Articles were identified for full-text review based on a screening of titles and abstracts and were excluded during this initial review if they focused on environmental exposures in the following populations: 1) Indigenous populations, 2) individuals <15 years of age, 3) pregnant women and associated negative birth outcomes, or 4) non-Canadian populations. Articles were also excluded if the primary focus was on exposures to environmental tobacco smoke, non-chemical occupational hazards, infectious diseases, noise and/or radiation. A full-text review of 78 identified articles systematically assessed how sex/gender and race/ethnicity were considered. Although 59% of studies stratified results by sex, less than half of these offered any explanation of differential exposures. Eighteen of the 78 studies (23%) used terms related to race/ethnicity in their participant descriptions. Of the studies that conducted subgroup analyses of exposure results by race/ethnicity (n=15), a total of 8 also included subgroup analysis by sex. Overall, 3 of the 78 (3%) articles reviewed analyzed environmental exposures as a function of sex/gender and race/ethnicity. The role of sex/gender and race/ethnicity in influencing environmental exposure levels among non-Indigenous Canadians has not been adequately addressed to date.

Transcriptome analyses of sex differential gene expression in brains of rare minnow (Gobiocypris rarus and effects of tributyltin exposure

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Ji-liang Zhang

2018-06-01

Full Text Available RNA-sequencing was used to identify sex-biased gene expression in brains of rare minnow (Gobiocypris rarus by comparing transcriptomic profiles between females and males. Furthermore, transcriptomic responses to 10 ng/L tributyltin (TBT in both male and female brains were also investigated to understand whether TBT affects the identified sex-biased genes. Differentially expressed genes (DEGs were identified using the IDEG6 web tool. In this article, we presented male- and female-biased DEGs, and up-regulated and down-regulated DEGs after TBT exposure. The raw reads data supporting the present analyses has been deposited in NCBI Sequence Read Archive (SRA, http://www.ncbi.nlm.nih.gov/Traces/sra with accession number PRJNA376634. The data presented in this article are related to the research article entitled “Transcriptomic analyses of sexual dimorphism of rare minnow (G. rarus brains and effects of tributyltin exposure” (doi: 10.1016/j.ecoenv.2018.02.049.

Juvenile exposure to vinclozolin shifts sex ratios and impairs reproductive capacity of zebrafish.

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Lor, Yer; Revak, Andrew; Weigand, Jenna; Hicks, Elisabeth; Howard, David R; King-Heiden, Tisha C

2015-12-01

Exposure to endocrine disruptors during critical periods of development can impact the sustainability of wild fish populations. Anti-androgenic compounds have received less attention, but are capable of modulating gonad differentiation and maturation, and impairing reproduction in fish. The fungicide vinclozolin (VZ) has been shown to impair reproduction in adult fish, but less is known about its effects following exposure earlier in development. Here we show that waterborne exposure to 400μg VZ/L during critical periods of sex differentiation (21-35 days post fertilization) permanently shifts sex ratios towards females, and alters the maturation of the gonad. Both fecundity and fertility were reduced, even when oogenesis and spermatogenesis recover and sperm motility is not altered. These results demonstrate the need to better understand the impacts of early exposure to anti-androgenic compounds on fish. Copyright © 2015 Elsevier Inc. All rights reserved.

Improving Student Understanding of Magmatic Differentiation Using an M&M Magma Chamber

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Wirth, K. R.

2003-12-01

Many students, especially those in introductory geology courses, have difficulty developing a deep understanding of the processes of magmatic differentiation. In particular, students often struggle to understand Bowen's reaction series and fractional crystallization. The process of fractional crystallization by gravity settling can be illustrated using a model magma chamber consisting of M&M's. In this model, each major cation (e.g., Si, Ti, Al, Fe, Mg, Ca, Na, K) is represented by a different color M&M; other kinds of differently colored or shaped pieces could also be used. Appropriate numbers of each color M&M are combined to approximate the cation proportions of a basaltic magma. Students then fractionate the magma by moving M&M's to the bottom of the magma chamber forming a series of cumulus layers; the M&M's are removed in the stoichiometric proportions of cations in the crystallizing minerals (e.g., olivine, pyroxene, feldspars, quartz, magnetite, ilmenite). Students observe the changing cation composition (proportions of colors of M&M's) in the cumulus layers and in the magma chamber and graph the results using spreadsheet software. More advanced students (e.g., petrology course) can classify the cumulates and resulting liquid after each crystallization step, and they can compare the model system with natural magmatic systems (e.g., absence of important fractionating phases, volatiles). Students who have completed this exercise generally indicate a positive experience and demonstrate increased understanding of Bowen's reaction series and fractionation processes. They also exhibit greater familiarity with mineral stoichiometry, classification, solid-solution in minerals, element behavior (e.g., incompatibility), and chemical variation diagrams. Other models (e.g., paths of equilibrium and fractional crystallization on phase diagrams) can also be used to illustrate differentiation processes in upper level courses (e.g., mineralogy and petrology).

MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure

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Kosten, Ilona J.; Spiekstra, Sander W. [Department of Dermatology, VU University Medical Center, Amsterdam (Netherlands); Gruijl, Tanja D. de [Department of Dermatology Medical Oncology, VU University Medical Center, Amsterdam (Netherlands); Gibbs, Susan, E-mail: s.gibbs@acta.nl [Department of Dermatology, VU University Medical Center, Amsterdam (Netherlands); Department of Oral Cell Biology, Academic Center for Dentistry (ACTA), Amsterdam (Netherlands)

2015-08-15

After allergen or irritant exposure, Langerhans cells (LC) undergo phenotypic changes and exit the epidermis. In this study we describe the unique ability of MUTZ-3 derived Langerhans cells (MUTZ-LC) to display similar phenotypic plasticity as their primary counterparts when incorporated into a physiologically relevant full-thickness skin equivalent model (SE-LC). We describe differences and similarities in the mechanisms regulating LC migration and plasticity upon allergen or irritant exposure. The skin equivalent consisted of a reconstructed epidermis containing primary differentiated keratinocytes and CD1a{sup +} MUTZ-LC on a primary fibroblast-populated dermis. Skin equivalents were exposed to a panel of allergens and irritants. Topical exposure to sub-toxic concentrations of allergens (nickel sulfate, resorcinol, cinnamaldehyde) and irritants (Triton X-100, SDS, Tween 80) resulted in LC migration out of the epidermis and into the dermis. Neutralizing antibody to CXCL12 blocked allergen-induced migration, whereas anti-CCL5 blocked irritant-induced migration. In contrast to allergen exposure, irritant exposure resulted in cells within the dermis becoming CD1a{sup −}/CD14{sup +}/CD68{sup +} which is characteristic of a phenotypic switch of MUTZ-LC to a macrophage-like cell in the dermis. This phenotypic switch was blocked with anti-IL-10. Mechanisms previously identified as being involved in LC activation and migration in native human skin could thus be reproduced in the in vitro constructed skin equivalent model containing functional LC. This model therefore provides a unique and relevant research tool to study human LC biology in situ under controlled in vitro conditions, and will provide a powerful tool for hazard identification, testing novel therapeutics and identifying new drug targets. - Highlights: • MUTZ-3 derived Langerhans cells integrated into skin equivalents are fully functional. • Anti-CXCL12 blocks allergen-induced MUTZ-LC migration. �

Presenteeism and absenteeism: differentiated understanding of related phenomena.

Science.gov (United States)

Gosselin, Eric; Lemyre, Louise; Corneil, Wayne

2013-01-01

In the past it was assumed that work attendance equated to performance. It now appears that health-related loss of productivity can be traced equally to workers showing up at work as well as to workers choosing not to. Presenteeism in the workplace, showing up for work while sick, seems now more prevalent than absenteeism. These findings are forcing organizations to reconsider their approaches regarding regular work attendance. Given this, and echoing recommendations in the literature, this study seeks to identify the main behavioral correlates of presenteeism and absenteeism in the workplace. Comparative analysis of the data from a representative sample of executives from the Public Service of Canada enables us to draw a unique picture of presenteeism and absenteeism with regards not only to the impacts of health disorders but also to the demographic, organizational, and individual factors involved. Results provide a better understanding of the similarities and differences between these phenomena, and more specifically, of the differentiated influence of certain variables. These findings provide food for thought and may pave the way to the development of new organizational measures designed to manage absenteeism without creating presenteeism.

In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats disrupts brain sexual differentiation

International Nuclear Information System (INIS)

Ikeda, Masahiko; Mitsui, Tetsuo; Setani, Kaoru; Tamura, Masashi; Kakeyama, Masaki; Sone, Hideko; Tohyama, Chiharu; Tomita, Takako

2005-01-01

The effects of in utero and lactational exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on brain sexual differentiation were investigated. TCDD was orally administered to pregnant Holtzman rats on gestation day (GD) 15, and the activity of brain aromatase, a key enzyme for sexual differentiation, was measured in offspring on postnatal day (PND) 2. Changes in sexual dimorphisms of saccharin preference and the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) were examined in adult offspring. In controls, litter means of brain aromatase activity were higher in males than in females. In utero exposure to 200 ng/kg TCDD significantly decreased the sex ratio of aromatase activity (male/female) on PND 2. Offspring were weaned on PND28 and the saccharin test was started on PND84. In controls, saccharin (0.25%) intake (g/kg body weight) was significantly higher in female offspring than in males. In utero exposure to 200 ng/kg TCDD significantly increased saccharin intake in male offspring compared with control males, whereas 800 ng/kg TCDD had no effect. Neither dose of TCDD influenced saccharin intake of female offspring. In controls, SDN-POA volume was significantly greater in males than in females at 14 weeks of age. Exposure to 200 ng/kg TCDD significantly decreased SDN-POA volume in males, whereas 800 ng/kg TCDD had no effect. Neither doses of TCDD influenced the SDN-POA volume in female offspring. These results suggest that in utero and lactational TCDD exposure dose-dependently induces demasculinization in male offspring by inhibiting brain aromatase activity in the hypothalamus-preoptic area during central nervous system development

Exposure to low level GSM 935 MHz radiofrequency fields does not induce apoptosis in proliferating or differentiated murine neuroblastoma cells

International Nuclear Information System (INIS)

Moquet, J.; Ainsbury, E.; Bouffler, S.; Lloyd, D.

2008-01-01

The aim of this study was to investigate whether radiofrequency (RF) fields characteristic of mobile phones at non-thermal levels can induce apoptosis in murine neuroblastoma (N2a) cells in both proliferating and differentiated states. Cells were exposed continuously for 24 h to one of the three 935-MHz RF signals: global system for mobile communication (GSM) basic, GSM talk and a continuous wave, unmodulated signal; all at a specific energy absorption rate of 2 W kg -1 . The measured increase in temperature of the cells due to the RF fields was around 0.06 deg. C. At a number of time points between 0 and 48 h post-exposure, the cells were assessed for apoptosis under a fluorescence microscope using three independent assays: Annexin V, caspase activation and in situ end-labelling. No statistically significant differences in apoptosis levels were observed between the exposed and sham-exposed cells using the three assays at any time point post-exposure. These data suggest that RF exposures, characteristic of GSM mobile phones, do not significantly affect the apoptosis levels in proliferating and differentiated murine neuroblastoma cell line N2a. (authors)

Differential microRNA expression in the prefrontal cortex of mouse offspring induced by glyphosate exposure during pregnancy and lactation.

Science.gov (United States)

Ji, Hua; Xu, Linhao; Wang, Zheng; Fan, Xinli; Wu, Lihui

2018-03-01

Glyphosate is the active ingredient in numerous herbicide formulations. The role of glyphosate in neurotoxicity has been reported in human and animal models. However, the detailed mechanism of the role of glyphosate in neuronal development remains unknown. Recently, several studies have reported evidence linking neurodevelopmental disorders (NDDs) with gestational glyphosate exposure. The current group previously identified microRNAs (miRNAs) that are associated with the etiology of NDDs, but their expression levels in the developing brain following glyphosate exposure have not been characterized. In the present study, miRNA expression patterns were evaluated in the prefrontal cortex (PFC) of 28 postnatal day mouse offspring following glyphosate exposure during pregnancy and lactation. An miRNA microarray detected 55 upregulated and 19 downregulated miRNAs in the PFC of mouse offspring, and 20 selected deregulated miRNAs were further evaluated by quantitative polymerase chain reaction (PCR). A total of 11 targets of these selected deregulated miRNAs were analyzed using bioinformatics. Gene Ontology (GO) terms associated with the relevant miRNAs included neurogenesis (GO:0050769), neuron differentiation (GO:0030182) and brain development (GO:0007420). The genes Cdkn1a, Numbl, Notch1, Fosl1 and Lef1 are involved in the Wnt and Notch signaling pathways, which are closely associated with neural development. PCR arrays for the mouse Wnt and Notch signaling pathways were used to validate the effects of glyphosate on the expression pattern of genes involved in the Wnt and Notch pathways. Nr4a2 and Wnt7b were downregulated, while Dkk1, Dixdc1, Runx1, Shh, Lef-1 and Axin2 were upregulated in the PFC of mice offspring following glyphosate exposure during pregnancy and lactation. These results indicated abnormalities of the Wnt/β-catenin and Notch pathways. These findings may be of particular interest for understanding the mechanism of glyphosate-induced neurotoxicity, as

AUTOMOTIVE DIESEL MAINTENANCE 1. UNIT XXII, I--MAINTAINING THE FUEL SYSTEM (PART I)--CUMMINS DIESEL ENGINE, II--UNDERSTANDING THE DIFFERENTIAL.

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Minnesota State Dept. of Education, St. Paul. Div. of Vocational and Technical Education.

THIS MODULE OF A 30-MODULE COURSE IS DESIGNED TO DEVELOP AN UNDERSTANDING OF THE FUNCTION AND MAINTENANCE OF THE DIESEL ENGINE FUEL SYSTEM AND DIFFERENTIAL DRIVE UNITS USED IN DIESEL POWERED VEHICLES. TOPICS ARE (1) FUEL SYSTEM COMPARISONS, (2) FUEL SYSTEM SUPPLY COMPONENTS, (3) FUEL SUPPLY SECTION MAINTENANCE, (4) FUNCTION OF THE DIFFERENTIAL,…

Exposures Related to House Dust Microbiota in a U.S. Farming Population.

Science.gov (United States)

Lee, Mi Kyeong; Carnes, Megan U; Butz, Natasha; Azcarate-Peril, M Andrea; Richards, Marie; Umbach, David M; Thorne, Peter S; Beane Freeman, Laura E; Peddada, Shyamal D; London, Stephanie J

2018-06-01

Environmental factors can influence the house dust microbiota, which may impact health outcomes. Little is known about how farming exposures impact the indoor microbiota. We aimed to identify exposures related to bacterial communities in house dust in a U.S. farming population. We used 16S rRNA amplicon sequencing to characterize bacterial communities in vacuumed dust samples from the bedrooms of a subset of 879 households of farmers and farmers' spouses enrolled in the Agricultural Lung Health Study (ALHS), a case-control study of asthma nested within the Agricultural Health Study (AHS) in North Carolina and Iowa. Information on current farming (past 12 mo), including both crop and animal farming, and other potential microbial sources was obtained via questionnaires. We used linear regression to evaluate associations between exposures and bacterial diversity within each sample, analysis of similarity (ANOSIM), and permutational multivariate analysis of variance (PERMANOVA) to identify exposures related to diversity between samples, and analysis of composition of microbiome to examine whether exposures related to diversity were also related to differential abundance of specific operational taxonomic units (OTUs). Current farming was positively associated with bacterial diversity in house dust, with or without adjustment for nonfarm exposures related to diversity, including presence of indoor pets, home condition, and season of dust collection. Many taxa exhibited differential abundance related to farming. Some taxa in the phyla Chloroflexi and Verrucomicrobia were associated [false discovery rate (FDR)<0.05] with farming but not with other nonfarm factors. Many taxa correlated with the concentration of house dust of endotoxin, commonly studied as a general marker of exposure to the farming environment. In this farming population, house dust microbiota differed by current farming status. Understanding the determinants of the indoor microbiota is the first step

Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates capacity of hematopoietic stem cells to undergo lymphocyte differentiation

International Nuclear Information System (INIS)

Ahrenhoerster, Lori S.; Tate, Everett R.; Lakatos, Peter A.; Wang, Xuexia; Laiosa, Michael D.

2014-01-01

The process of hematopoiesis, characterized by long-term self-renewal and multi-potent lineage differentiation, has been shown to be regulated in part by the ligand-activated transcription factor known as the aryl hydrocarbon receptor (AHR). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a ubiquitous contaminant and the most potent AHR agonist, also modulates regulation of adult hematopoietic stem and progenitor cell (HSC/HPC) homeostasis. However, the effect of developmental TCDD exposure on early life hematopoiesis has not been fully explored. Given the inhibitory effects of TCDD on hematopoiesis and lymphocyte development, we hypothesized that in utero exposure to TCDD would alter the functional capacity of fetal HSC/HPCs to complete lymphocyte differentiation. To test this hypothesis, we employed a co-culture system designed to facilitate the maturation of progenitor cells to either B or T lymphocytes. Furthermore, we utilized an innovative limiting dilution assay to precisely quantify differences in lymphocyte differentiation between HSC/HPCs obtained from fetuses of dams exposed to 3 μg/kg TCDD or control. We found that the AHR is transcribed in yolk sac hematopoietic cells and is transcriptionally active as early as gestational day (GD) 7.5. Furthermore, the number of HSC/HPCs present in the fetal liver on GD 14.5 was significantly increased in fetuses whose mothers were exposed to TCDD throughout pregnancy. Despite this increase in HSC/HPC cell number, B and T lymphocyte differentiation is decreased by approximately 2.5 fold. These findings demonstrate that inappropriate developmental AHR activation in HSC/HPCs adversely impacts lymphocyte differentiation and may have consequences for lymphocyte development in the bone marrow and thymus later in life

Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates capacity of hematopoietic stem cells to undergo lymphocyte differentiation

Energy Technology Data Exchange (ETDEWEB)

Ahrenhoerster, Lori S.; Tate, Everett R.; Lakatos, Peter A. [Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee (United States); Program in Environmental and Occupational Health, Milwaukee, WI 53211 (United States); Wang, Xuexia [Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee (United States); Program in Biostatistics, Milwaukee, WI 53211 (United States); Laiosa, Michael D., E-mail: laiosa@uwm.edu [Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee (United States); Program in Environmental and Occupational Health, Milwaukee, WI 53211 (United States)

2014-06-01

The process of hematopoiesis, characterized by long-term self-renewal and multi-potent lineage differentiation, has been shown to be regulated in part by the ligand-activated transcription factor known as the aryl hydrocarbon receptor (AHR). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a ubiquitous contaminant and the most potent AHR agonist, also modulates regulation of adult hematopoietic stem and progenitor cell (HSC/HPC) homeostasis. However, the effect of developmental TCDD exposure on early life hematopoiesis has not been fully explored. Given the inhibitory effects of TCDD on hematopoiesis and lymphocyte development, we hypothesized that in utero exposure to TCDD would alter the functional capacity of fetal HSC/HPCs to complete lymphocyte differentiation. To test this hypothesis, we employed a co-culture system designed to facilitate the maturation of progenitor cells to either B or T lymphocytes. Furthermore, we utilized an innovative limiting dilution assay to precisely quantify differences in lymphocyte differentiation between HSC/HPCs obtained from fetuses of dams exposed to 3 μg/kg TCDD or control. We found that the AHR is transcribed in yolk sac hematopoietic cells and is transcriptionally active as early as gestational day (GD) 7.5. Furthermore, the number of HSC/HPCs present in the fetal liver on GD 14.5 was significantly increased in fetuses whose mothers were exposed to TCDD throughout pregnancy. Despite this increase in HSC/HPC cell number, B and T lymphocyte differentiation is decreased by approximately 2.5 fold. These findings demonstrate that inappropriate developmental AHR activation in HSC/HPCs adversely impacts lymphocyte differentiation and may have consequences for lymphocyte development in the bone marrow and thymus later in life.

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

International Nuclear Information System (INIS)

Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

2015-01-01

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner. �

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

Energy Technology Data Exchange (ETDEWEB)

Menelaou, Evdokia; Paul, Latoya T. [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Perera, Surangi N. [Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States); Svoboda, Kurt R., E-mail: svobodak@uwm.edu [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States)

2015-04-01

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner. �

Differential proteomic expression of human placenta and fetal development following e-waste lead and cadmium exposure in utero

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Xu, Long; Ge, Jingjing; Huo, Xia; Zhang, Yuling [Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041 (China); Lau, Andy T.Y. [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041 (China); Xu, Xijin, E-mail: xuxj@stu.edu.cn [Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041 (China)

2016-04-15

ABSTRACT: Prenatal exposure to lead (Pb) and cadmium (Cd) has been associated with a series of physiological problems resulting in fetal growth restriction. We aimed to investigate the effects of Pb and Cd exposure on placental function and the potential mechanisms involved in fetal development. Placental specimens and questionnaires were collected from an e-waste area and a reference area in China. Two-dimensional electrophoresis combined with MALDI-TOF-MS/MS and molecular network relationship were performed to analyze differentially expressed proteins using a compositing sample pool. Compared with the reference group, the exposed group exhibited significantly higher levels of placental Pb and Cd (p < 0.01), shorter body length and higher gestational age (p < 0.01). After bivariate adjustment in a linear regression model, decreases of 205.05 g in weight and 0.44 cm in body length were associated with a 10 ng/g wt increase in placental Cd. Pb showed a negative trend but lacked statistical significance. Proteomic analysis showed 32 differentially-expressed proteins and were predominantly involved in protein translocation, cytoskeletal structure, and energy metabolism. Fumarate hydratase was down-regulated in the exposed placenta tissues and validated by ELISA. Alterations in placental proteome suggest that imbalances in placental mitochondria respiration might be a vital pathway targeting fetal growth restriction induced by exposure to Cd. - Highlights: • The placental Pb and Cd levels were higher in the e-waste polluted area. • Proteome in placenta tissues was performed by two-dimensional gel electrophoresis. • Cd exposure in the placenta was associated with the reduced fetal development. • 32 proteins covered in translocation, energy metabolism and cytoskeletal structure. • Dysregulated mitochondrial respiration may act in the Cd-reduced fetal development.

Differential proteomic expression of human placenta and fetal development following e-waste lead and cadmium exposure in utero

International Nuclear Information System (INIS)

Xu, Long; Ge, Jingjing; Huo, Xia; Zhang, Yuling; Lau, Andy T.Y.; Xu, Xijin

2016-01-01

ABSTRACT: Prenatal exposure to lead (Pb) and cadmium (Cd) has been associated with a series of physiological problems resulting in fetal growth restriction. We aimed to investigate the effects of Pb and Cd exposure on placental function and the potential mechanisms involved in fetal development. Placental specimens and questionnaires were collected from an e-waste area and a reference area in China. Two-dimensional electrophoresis combined with MALDI-TOF-MS/MS and molecular network relationship were performed to analyze differentially expressed proteins using a compositing sample pool. Compared with the reference group, the exposed group exhibited significantly higher levels of placental Pb and Cd (p < 0.01), shorter body length and higher gestational age (p < 0.01). After bivariate adjustment in a linear regression model, decreases of 205.05 g in weight and 0.44 cm in body length were associated with a 10 ng/g wt increase in placental Cd. Pb showed a negative trend but lacked statistical significance. Proteomic analysis showed 32 differentially-expressed proteins and were predominantly involved in protein translocation, cytoskeletal structure, and energy metabolism. Fumarate hydratase was down-regulated in the exposed placenta tissues and validated by ELISA. Alterations in placental proteome suggest that imbalances in placental mitochondria respiration might be a vital pathway targeting fetal growth restriction induced by exposure to Cd. - Highlights: • The placental Pb and Cd levels were higher in the e-waste polluted area. • Proteome in placenta tissues was performed by two-dimensional gel electrophoresis. • Cd exposure in the placenta was associated with the reduced fetal development. • 32 proteins covered in translocation, energy metabolism and cytoskeletal structure. • Dysregulated mitochondrial respiration may act in the Cd-reduced fetal development.

PERINATAL EXPOSURE TO THE PHTHALATES DEHP, BBP AND DINP, BUT NOT DEP, DMP OR DOTP ALTERS SEXUAL DIFFERENTIATION OF THE MALE RAT

Science.gov (United States)

In mammals, exposure to antiandrogenic chemicals during sexual differentiation can produce malformations of the reproductive tract. Perinatal administration of AR antagonists like vinclozolin and procymidone or chemicals like di (2-bis) ethylhexyl phthalate (DEHP), that inhibit ...

Childhood adversity and adult depression among the incarcerated: differential exposure and vulnerability by race/ethnicity and gender.

Science.gov (United States)

Roxburgh, Susan; MacArthur, Kelly Rhea

2014-08-01

The relationship between childhood adversity and adult depression is well-established but less is known about the association between childhood adversity and adult depression among the incarcerated. In this paper, we examine differential exposure and vulnerability to childhood adversity by race/ethnicity and gender on adult depression among the incarcerated in the United States. We address three research questions: does exposure to childhood adverse experiences vary by race/ethnicity and gender? Is there an association between these childhood adverse events and depression and does the strength of the association vary by the specific adverse experiences? And does vulnerability to childhood adversity vary by gender and race/ethnicity? Using the 2004 Survey of Inmates in State and Federal Correctional Facilities (SI-SFCF), we measure four key childhood adverse events - parental/caretaker substance abuse, physical assault, having been placed in foster care, and sexual assault. We use ordinary least squares regression and a series of interaction effect analyses to examine differential exposure and vulnerability to the four childhood adverse experiences by race/ethnicity and gender. Incarcerated women are more likely to report parental substance abuse, but all inmates/prisoners are similarly vulnerable to this experience. For the other three adverse experiences measured, we find that there are important racial/ethnic and gender differences in both exposure and vulnerability. African American men and women are more vulnerable to the effects of physical and sexual victimization than White and Hispanic men and women. Women are much more likely to be exposed to sexual victimization, but men who report this experience are significantly more depressed. Hispanic women and White men and women are more likely to report foster care, but all inmates/prisoners who report foster care experiences are significantly more depressed than other inmates/prisoners, with the exception of

Differential pulmonary and cardiac effects of pulmonary exposure to a panel of particulate matter-associated metals

International Nuclear Information System (INIS)

Wallenborn, J. Grace; Schladweiler, Mette J.; Richards, Judy H.; Kodavanti, Urmila P.

2009-01-01

Biological mechanisms underlying the association between particulate matter (PM) exposure and increased cardiovascular health effects are under investigation. Water-soluble metals reaching systemic circulation following pulmonary exposure are likely exerting a direct effect. However, it is unclear whether specific PM-associated metals may be driving this. We hypothesized that exposure to equimolar amounts of five individual PM-associated metals would cause differential pulmonary and cardiac effects. We exposed male WKY rats (14 weeks old) via a single intratracheal instillation (IT) to saline or 1 μmol/kg body weight of zinc, nickel, vanadium, copper, or iron in sulfate form. Responses were analyzed 4, 24, 48, or 96 h after exposure. Pulmonary effects were assessed by bronchoalveolar lavage fluid levels of total cells, macrophages, neutrophils, protein, albumin, and activities of lactate dehydrogenase, γ-glutamyl transferase, and n-acetyl glucosaminidase. Copper induced earlier pulmonary injury/inflammation, while zinc and nickel produced later effects. Vanadium or iron exposure induced minimal pulmonary injury/inflammation. Zinc, nickel, or copper increased serum cholesterol, red blood cells, and white blood cells at different time points. IT of nickel and copper increased expression of metallothionein-1 (MT-1) in the lung. Zinc, nickel, vanadium, and iron increased hepatic MT-1 expression. No significant changes in zinc transporter-1 (ZnT-1) expression were noted in the lung or liver; however, zinc increased cardiac ZnT-1 at 24 h, indicating a possible zinc-specific cardiac effect. Nickel exposure induced an increase in cardiac ferritin 96 h after IT. This data set demonstrating metal-specific cardiotoxicity is important in linking metal-enriched anthropogenic PM sources with adverse health effects.

Understanding and Predicting Effect of Sodium Exposure on Microstructure of Grade 91 Steel

Energy Technology Data Exchange (ETDEWEB)

Li, Meimei [Argonne National Lab. (ANL), Argonne, IL (United States); Natesan, K. [Argonne National Lab. (ANL), Argonne, IL (United States); Chen, Wei-Ying [Argonne National Lab. (ANL), Argonne, IL (United States)

2017-08-01

This report provides an update on the understanding of the effect of sodium exposures on microstructure and tensile properties of Grade 91 (G91) steel in support of the design and operation of G91 components in sodium-cooled fast reactors (SFRs). The report is a Level 3 deliverable in FY17 (M3AT-17AN1602018), under the Work Package AT-17AN160201, “SFR Materials Testing” performed by the Argonne National Laboratory (ANL), as part of the Advanced Reactor Technologies Program.

Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells

DEFF Research Database (Denmark)

Dreyer-Andersen, Nanna; Almeida, Ana Sofia; Jensen, Pia

2018-01-01

Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem...... cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting...... in Parkinson's disease....

New Horizons in Enhancing the Proliferation and Differentiation of Neural Stem Cells Using Stimulatory Effects of the Short Time Exposure to Radiofrequency Radiation.

Science.gov (United States)

Eghlidospour, M; Mortazavi, S M J; Yousefi, F; Mortazavi, S A R

2015-09-01

Mobile phone use and wireless communication technology have grown explosively over the past decades. This rapid growth has caused widespread global concern about the potential detrimental effects of this technology on human health. Stem cells generate specialized cell types of the tissue in which they reside through normal differentiation pathways. Considering the undeniable importance of stem cells in modern medicine, numerous studies have been performed on the effects of ionizing and non-ionizing radiation on cellular processes such as: proliferation, differentiation, cell cycle and DNA repair processes. We have conducted extensive studies on beneficial (stimulatory) or detrimental biological effects of exposure to different sources of electromagnetic fields such as mobile phones, mobile phone base stations, mobile phone jammers, radar systems, magnetic resonance imaging (MRI) systems and dentistry cavitrons over the past years. In this article, recent studies on the biological effects of non-ionizing electromagnetic radiation in the range of radiofrequency (RF) on some important features of stem cells such as their proliferation and differentiation are reviewed. Studies reviewed in this paper indicate that the stimulatory or inhibitory effects of RF radiation on the proliferation and differentiation of stem cells depend on various factors such as the biological systems, experiment conditions, the frequency and intensity of RF and the duration of exposure.

Differential Gene Expression in Explanted Human Retinal Pigment Epithelial Cells 24-Hours Post-Exposure to 532 nm, 3.0 ns Pulsed Laser Light and 1064 nm, 170 ps Pulsed Laser Light 12-Hours Post-Exposure: Results Compendium

National Research Council Canada - National Science Library

Obringer, John

2004-01-01

.... We assessed the sublethal insult to human retinal pigment epithelial cells using a cadaver organ donor explant system for genes differentially expressed 12 and 24 hours post- exposure using gene...

Extremely Low-Frequency Electromagnetic Fields Promote In Vitro Neuronal Differentiation and Neurite Outgrowth of Embryonic Neural Stem Cells via Up-Regulating TRPC1

Science.gov (United States)

Ma, Qinlong; Chen, Chunhai; Deng, Ping; Zhu, Gang; Lin, Min; Zhang, Lei; Xu, Shangcheng; He, Mindi; Lu, Yonghui; Duan, Weixia; Pi, Huifeng; Cao, Zhengwang; Pei, Liping; Li, Min; Liu, Chuan; Zhang, Yanwen; Zhong, Min; Zhou, Zhou; Yu, Zhengping

2016-01-01

Exposure to extremely low-frequency electromagnetic fields (ELF-EMFs) can enhance hippocampal neurogenesis in adult mice. However, little is focused on the effects of ELF-EMFs on embryonic neurogenesis. Here, we studied the potential effects of ELF-EMFs on embryonic neural stem cells (eNSCs). We exposed eNSCs to ELF-EMF (50 Hz, 1 mT) for 1, 2, and 3 days with 4 hours per day. We found that eNSC proliferation and maintenance were significantly enhanced after ELF-EMF exposure in proliferation medium. ELF-EMF exposure increased the ratio of differentiated neurons and promoted the neurite outgrowth of eNSC-derived neurons without influencing astrocyes differentiation and the cell apoptosis. In addition, the expression of the proneural genes, NeuroD and Ngn1, which are crucial for neuronal differentiation and neurite outgrowth, was increased after ELF-EMF exposure. Moreover, the expression of transient receptor potential canonical 1 (TRPC1) was significantly up-regulated accompanied by increased the peak amplitude of intracellular calcium level induced by ELF-EMF. Furthermore, silencing TRPC1 expression eliminated the up-regulation of the proneural genes and the promotion of neuronal differentiation and neurite outgrowth induced by ELF-EMF. These results suggest that ELF-EMF exposure promotes the neuronal differentiation and neurite outgrowth of eNSCs via up-regulation the expression of TRPC1 and proneural genes (NeuroD and Ngn1). These findings also provide new insights in understanding the effects of ELF-EMF exposure on embryonic brain development. PMID:26950212

Sex-Dependent Effects of Developmental Lead Exposure on the Brain

Science.gov (United States)

Singh, Garima; Singh, Vikrant; Sobolewski, Marissa; Cory-Slechta, Deborah A.; Schneider, Jay S.

2018-01-01

The role of sex as an effect modifier of developmental lead (Pb) exposure has until recently received little attention. Lead exposure in early life can affect brain development with persisting influences on cognitive and behavioral functioning, as well as, elevated risks for developing a variety of diseases and disorders in later life. Although both sexes are affected by Pb exposure, the incidence, manifestation, and severity of outcomes appears to differ in males and females. Results from epidemiologic and animal studies indicate significant effect modification by sex, however, the results are not consistent across studies. Unfortunately, only a limited number of human epidemiological studies have included both sexes in independent outcome analyses limiting our ability to draw definitive conclusions regarding sex-differentiated outcomes. Additionally, due to various methodological differences across studies, there is still not a good mechanistic understanding of the molecular effects of lead on the brain and the factors that influence differential responses to Pb based on sex. In this review, focused on prenatal and postnatal Pb exposures in humans and animal models, we discuss current literature supporting sex differences in outcomes in response to Pb exposure and explore some of the ideas regarding potential molecular mechanisms that may contribute to sex-related differences in outcomes from developmental Pb exposure. The sex-dependent variability in outcomes from developmental Pb exposure may arise from a combination of complex factors, including, but not limited to, intrinsic sex-specific molecular/genetic mechanisms and external risk factors including sex-specific responses to environmental stressors which may act through shared epigenetic pathways to influence the genome and behavioral output. PMID:29662502

Sex-Dependent Effects of Developmental Lead Exposure on the Brain

Directory of Open Access Journals (Sweden)

Garima Singh

2018-03-01

Full Text Available The role of sex as an effect modifier of developmental lead (Pb exposure has until recently received little attention. Lead exposure in early life can affect brain development with persisting influences on cognitive and behavioral functioning, as well as, elevated risks for developing a variety of diseases and disorders in later life. Although both sexes are affected by Pb exposure, the incidence, manifestation, and severity of outcomes appears to differ in males and females. Results from epidemiologic and animal studies indicate significant effect modification by sex, however, the results are not consistent across studies. Unfortunately, only a limited number of human epidemiological studies have included both sexes in independent outcome analyses limiting our ability to draw definitive conclusions regarding sex-differentiated outcomes. Additionally, due to various methodological differences across studies, there is still not a good mechanistic understanding of the molecular effects of lead on the brain and the factors that influence differential responses to Pb based on sex. In this review, focused on prenatal and postnatal Pb exposures in humans and animal models, we discuss current literature supporting sex differences in outcomes in response to Pb exposure and explore some of the ideas regarding potential molecular mechanisms that may contribute to sex-related differences in outcomes from developmental Pb exposure. The sex-dependent variability in outcomes from developmental Pb exposure may arise from a combination of complex factors, including, but not limited to, intrinsic sex-specific molecular/genetic mechanisms and external risk factors including sex-specific responses to environmental stressors which may act through shared epigenetic pathways to influence the genome and behavioral output.

Understanding the Impact of Exposure Patterns on Risks from Combined Exposures to Multiple Chemicals

Science.gov (United States)

The talk was invited so there is no formal abstract. However, the focus of the talk is on the use of exposure information in the evaluation of risks from combined exposures to chemicals. The talk presents a bit of history and several case studies. All empirical data presented hav...

Abstract methods in partial differential equations

CERN Document Server

Carroll, Robert W

2012-01-01

Detailed, self-contained treatment examines modern abstract methods in partial differential equations, especially abstract evolution equations. Suitable for graduate students with some previous exposure to classical partial differential equations. 1969 edition.

Investigating Epigenetic Effects of Prenatal Exposure to Toxic Metals in Newborns: Challenges and Benefits.

Science.gov (United States)

Nye, Monica D; Fry, Rebecca C; Hoyo, Cathrine; Murphy, Susan K

2014-01-01

Increasing evidence suggest that epigenetic alterations can greatly impact human health, and that epigenetic mechanisms (DNA methylation, histone modifications, and microRNAs) may be particularly relevant in responding to environmental toxicant exposure early in life. The epigenome plays a vital role in embryonic development, tissue differentiation and disease development by controlling gene expression. In this review we discuss what is currently known about epigenetic alterations in response to prenatal exposure to inorganic arsenic (iAs) and lead (Pb), focusing specifically on their effects on DNA methylation. We then describe how epigenetic alterations are being studied in newborns as potential biomarkers of in utero environmental toxicant exposure, and the benefits and challenges of this approach. In summary, the studies highlighted herein indicate how epigenetic mechanisms are impacted by early life exposure to iAs and Pb, and the research that is being done to move towards understanding the relationships between toxicant-induced epigenetic alterations and disease development. Although much remains unknown, several groups are working to understand the correlative and causal effects of early life toxic metal exposure on epigenetic changes and how these changes may result in later development of disease.

Rethinking pedagogy for second-order differential equations: a simplified approach to understanding well-posed problems

Science.gov (United States)

Tisdell, Christopher C.

2017-07-01

Knowing an equation has a unique solution is important from both a modelling and theoretical point of view. For over 70 years, the approach to learning and teaching 'well posedness' of initial value problems (IVPs) for second- and higher-order ordinary differential equations has involved transforming the problem and its analysis to a first-order system of equations. We show that this excursion is unnecessary and present a direct approach regarding second- and higher-order problems that does not require an understanding of systems.

Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

Energy Technology Data Exchange (ETDEWEB)

Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel; Chapman, Shira; Bloch-Shilderman, Eugenia; Grauer, Ettie, E-mail: ettieg@iibr.gov.il

2016-11-01

Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. In all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.

Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

International Nuclear Information System (INIS)

Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel; Chapman, Shira; Bloch-Shilderman, Eugenia; Grauer, Ettie

2016-01-01

Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. In all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.

Co-Culture with Human Osteoblasts and Exposure to Extremely Low Frequency Pulsed Electromagnetic Fields Improve Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells

Directory of Open Access Journals (Sweden)

Sabrina Ehnert

2018-03-01

Full Text Available Human adipose-derived mesenchymal stem cells (Ad-MSCs have been proposed as suitable option for cell-based therapies to support bone regeneration. In the bone environment, Ad-MSCs will receive stimuli from resident cells that may favor their osteogenic differentiation. There is recent evidence that this process can be further improved by extremely low frequency pulsed electromagnetic fields (ELF-PEMFs. Thus, the project aimed at (i investigating whether co-culture conditions of human osteoblasts (OBs and Ad-MSCs have an impact on their proliferation and osteogenic differentiation; (ii whether this effect can be further improved by repetitive exposure to two specific ELF-PEMFs (16 and 26 Hz; (iii and the effect of these ELF-PEMFs on human osteoclasts (OCs. Osteogenic differentiation was improved by co-culturing OBs and Ad-MSCs when compared to the individual mono-cultures. An OB to Ad-MSC ratio of 3:1 had best effects on total protein content, alkaline phosphatase (AP activity, and matrix mineralization. Osteogenic differentiation was further improved by both ELF-PEMFs investigated. Interestingly, only repetitive exposure to 26 Hz ELF-PEMF increased Trap5B activity in OCs. Considering this result, a treatment with gradually increasing frequency might be of interest, as the lower frequency (16 Hz could enhance bone formation, while the higher frequency (26 Hz could enhance bone remodeling.

Exposure to carbon ions triggers pro-inflammatory signals, changes in homeostasis and epidermal tissue organization to a similar extent as photons

Directory of Open Access Journals (Sweden)

Palma eSimoniello

2016-01-01

Full Text Available The increasing application of charged particles in radiotherapy requires a deeper understanding of early and late side effects occurring in skin, which is exposed in all radiation treatments. We measured cellular and molecular changes related to the early inflammatory response of human skin irradiated with carbon ions, in particular cell death induction and changes in differentiation and proliferation of epidermal cells during the first days after exposure.Model systems for human skin from healthy donors of different complexity, i.e. keratinocytes, co-culture of skin cells, 3D skin equivalent and skin explants, were used to investigate the alterations induced by carbon ions (spread-out Bragg-peak, dose averaged LET 100 keV/µm in comparison to X-ray and UV-B exposure. After exposure to ionizing radiation, in none of the model systems apoptosis/necrosis was observed. Carbon ions triggered inflammatory signalling and accelerated differentiation of keratinocytes to a similar extent as X-rays at the same doses. High doses of carbon ions were more effective than X-rays in reducing proliferation and inducing abnormal differentiation. In contrast, changes identified following low dose exposure (≤ 0.5 Gy were induced more effectively after X-ray exposure, i.e. enhanced proliferation and change in the polarity of basal cells.

Modelling effects of diquat under realistic exposure patterns in genetically differentiated populations of the gastropod Lymnaea stagnalis.

Science.gov (United States)

Ducrot, Virginie; Péry, Alexandre R R; Lagadic, Laurent

2010-11-12

Pesticide use leads to complex exposure and response patterns in non-target aquatic species, so that the analysis of data from standard toxicity tests may result in unrealistic risk forecasts. Developing models that are able to capture such complexity from toxicity test data is thus a crucial issue for pesticide risk assessment. In this study, freshwater snails from two genetically differentiated populations of Lymnaea stagnalis were exposed to repeated acute applications of environmentally realistic concentrations of the herbicide diquat, from the embryo to the adult stage. Hatching rate, embryonic development duration, juvenile mortality, feeding rate and age at first spawning were investigated during both exposure and recovery periods. Effects of diquat on mortality were analysed using a threshold hazard model accounting for time-varying herbicide concentrations. All endpoints were significantly impaired at diquat environmental concentrations in both populations. Snail evolutionary history had no significant impact on their sensitivity and responsiveness to diquat, whereas food acted as a modulating factor of toxicant-induced mortality. The time course of effects was adequately described by the model, which thus appears suitable to analyse long-term effects of complex exposure patterns based upon full life cycle experiment data. Obtained model outputs (e.g. no-effect concentrations) could be directly used for chemical risk assessment.

Differential equations for dummies

CERN Document Server

Holzner, Steven

2008-01-01

The fun and easy way to understand and solve complex equations Many of the fundamental laws of physics, chemistry, biology, and economics can be formulated as differential equations. This plain-English guide explores the many applications of this mathematical tool and shows how differential equations can help us understand the world around us. Differential Equations For Dummies is the perfect companion for a college differential equations course and is an ideal supplemental resource for other calculus classes as well as science and engineering courses. It offers step-by-step techniques, practical tips, numerous exercises, and clear, concise examples to help readers improve their differential equation-solving skills and boost their test scores.

Differential effects of magnetic field exposure from domestic power supply on loco motor and exploratory behavior of an adult rat

International Nuclear Information System (INIS)

Anandavadivel, A.; Caleo, M.

2011-01-01

In the present study, we have examined the low intense magnetic field exposed on adult rats to understand effect of several behavioral parameters. The rats are tested in the open field and spontaneous alternation task after either a single or chronic exposure to the magnetic field. We found that magnetic field exposure had no effect on locomotor behavior in the adult. However, the exploratory behavior of adult rats in the open field was significantly affected. Indeed, we found a consistent increase in behavior performance viz. exploration time and number of exploration events in rats exposed to magnetic field. Our results demonstrate behavioral changes after magnetic field exposure in adult subjects. This also suggests possible deleterious effects of magnetic field exposure in the brain. (author)

Association of direct exposure to terrorism, media exposure to terrorism, and other trauma with emotional and behavioral problems in preschool children.

Science.gov (United States)

Wang, Yanping; Nomura, Yoko; Pat-Horenczyk, Ruth; Doppelt, Osnat; Abramovitz, Robert; Brom, Daniel; Chemtob, Claude

2006-12-01

This study examined the differential impact of various types of trauma exposure on emotional and behavioral problems in preschool children. Participants were 95 mothers of 1- to 4-year-old children in Israel. Results suggested a differential pattern of associations between the types of trauma exposure (i.e., direct exposure to terrorism, media exposure to terrorism, and other trauma) and children's internalizing and externalizing problems. This line of research is important for the identification of risk factors and the development of effective prevention and intervention strategies to promote resilience in preschool children exposed to specific type(s) of trauma.

Arsenic inhibits hedgehog signaling during P19 cell differentiation

Energy Technology Data Exchange (ETDEWEB)

Liu, Jui Tung [Environmental Toxicology Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Bain, Lisa J., E-mail: lbain@clemson.edu [Environmental Toxicology Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Department of Biological Sciences, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States)

2014-12-15

Arsenic is a toxicant found in ground water around the world, and human exposure mainly comes from drinking water or from crops grown in areas containing arsenic in soils or water. Epidemiological studies have shown that arsenic exposure during development decreased intellectual function, reduced birth weight, and altered locomotor activity, while in vitro studies have shown that arsenite decreased muscle and neuronal cell differentiation. The sonic hedgehog (Shh) signaling pathway plays an important role during the differentiation of both neurons and skeletal muscle. The purpose of this study was to investigate whether arsenic can disrupt Shh signaling in P19 mouse embryonic stem cells, leading to changes muscle and neuronal cell differentiation. P19 embryonic stem cells were exposed to 0, 0.25, or 0.5 μM of sodium arsenite for up to 9 days during cell differentiation. We found that arsenite exposure significantly reduced transcript levels of genes in the Shh pathway in both a time and dose-dependent manner. This included the Shh ligand, which was decreased 2- to 3-fold, the Gli2 transcription factor, which was decreased 2- to 3-fold, and its downstream target gene Ascl1, which was decreased 5-fold. GLI2 protein levels and transcriptional activity were also reduced. However, arsenic did not alter GLI2 primary cilium accumulation or nuclear translocation. Moreover, additional extracellular SHH rescued the inhibitory effects of arsenic on cellular differentiation due to an increase in GLI binding activity. Taken together, we conclude that arsenic exposure affected Shh signaling, ultimately decreasing the expression of the Gli2 transcription factor. These results suggest a mechanism by which arsenic disrupts cell differentiation. - Highlights: • Arsenic exposure decreases sonic hedgehog pathway-related gene expression. • Arsenic decreases GLI2 protein levels and transcriptional activity in P19 cells. • Arsenic exposure does not alter the levels of SHH

Socioeconomic and urban-rural differentials in exposure to air pollution and mortality burden in England.

Science.gov (United States)

Milojevic, Ai; Niedzwiedz, Claire L; Pearce, Jamie; Milner, James; MacKenzie, Ian A; Doherty, Ruth M; Wilkinson, Paul

2017-10-06

Socioeconomically disadvantaged populations often have higher exposures to particulate air pollution, which can be expected to contribute to differentials in life expectancy. We examined socioeconomic differentials in exposure and air pollution-related mortality relating to larger scale (5 km resolution) variations in background concentrations of selected pollutants across England. Ozone and particulate matter (sub-divided into PM 10 , PM 2.5 , PM 2.5-10 , primary, nitrate and sulphate PM 2.5 ) were simulated at 5 km horizontal resolution using an atmospheric chemistry transport model (EMEP4UK). Annual mean concentrations of these pollutants were assigned to all 1,202,578 residential postcodes in England, which were classified by urban-rural status and socioeconomic deprivation based on the income and employment domains of the 2010 English Index of Multiple Deprivation for the Lower-level Super Output Area of residence. We used life table methods to estimate PM 2.5 -attributable life years (LYs) lost in both relative and absolute terms. Concentrations of the most particulate fractions, but not of nitrate PM 2.5 or ozone, were modestly higher in areas of greater socioeconomic deprivation. Relationships between pollution level and socioeconomic deprivation were non-linear and varied by urban-rural status. The pattern of PM 2.5 concentrations made only a small contribution to the steep socioeconomic gradient in LYs lost due to PM 2.5 per 10 3 population, which primarily was driven by the steep socioeconomic gradient in underlying mortality rates. In rural areas, the absolute burden of air pollution-related LYs lost was lowest in the most deprived deciles. Air pollution shows modest socioeconomic patterning at 5 km resolution in England, but absolute attributable mortality burdens are strongly related to area-level deprivation because of underlying mortality rates. Measures that cause a general reduction in background concentrations of air pollution may modestly

Ordinary differential equations

CERN Document Server

Greenberg, Michael D

2014-01-01

Features a balance between theory, proofs, and examples and provides applications across diverse fields of study Ordinary Differential Equations presents a thorough discussion of first-order differential equations and progresses to equations of higher order. The book transitions smoothly from first-order to higher-order equations, allowing readers to develop a complete understanding of the related theory. Featuring diverse and interesting applications from engineering, bioengineering, ecology, and biology, the book anticipates potential difficulties in understanding the various solution steps

Human immunotoxicologic markers of chemical exposures: preliminary validation studies.

Science.gov (United States)

Wartenberg, D; Laskin, D; Kipen, H

1993-01-01

The circulating cells of the immune system are sensitive to environmental contaminants, and effects are often manifested as changes in the cell surface differentiation antigens of affected populations of cells, particularly lymphocytes. In this investigation, we explore the likelihood that variation in the expression of the surface markers of immune cells can be used as an index of exposure to toxic chemicals. We recruited 38 healthy New Jersey men to study pesticides effects: 19 orchard farmers (high exposure); 13 berry farmers (low exposure); and 6 hardware store owners (no exposure). Immunophenotyping was performed assaying the following cell surface antigens: CD2, CD4, CD8, CD14, CD20, CD26, CD29, CD45R, CD56, and PMN. Data were analyzed using univariate and multivariate methods. There were no significant differences among the groups with respect to routine medical histories, physical examinations, or routine laboratory parameters. No striking differences between groups were seen in univariate tests. Multivariate tests suggested some differences among groups and limited ability to correctly classify individuals based on immunophenotyping results. Immunophenotyping represents a fruitful area of research for improved exposure classification. Work is needed both on mechanistic understanding of the patterns observed and on the statistical interpretation of these patterns.

Differential psychological impact of internet exposure on Internet addicts.

Directory of Open Access Journals (Sweden)

Michela Romano

Full Text Available The study explored the immediate impact of internet exposure on the mood and psychological states of internet addicts and low internet-users. Participants were given a battery of psychological tests to explore levels of internet addiction, mood, anxiety, depression, schizotypy, and autism traits. They were then given exposure to the internet for 15 min, and re-tested for mood and current anxiety. Internet addiction was associated with long-standing depression, impulsive nonconformity, and autism traits. High internet-users also showed a pronounced decrease in mood following internet use compared to the low internet-users. The immediate negative impact of exposure to the internet on the mood of internet addicts may contribute to increased usage by those individuals attempting to reduce their low mood by re-engaging rapidly in internet use.

Differential psychological impact of internet exposure on Internet addicts.

Science.gov (United States)

Romano, Michela; Osborne, Lisa A; Truzoli, Roberto; Reed, Phil

2013-01-01

The study explored the immediate impact of internet exposure on the mood and psychological states of internet addicts and low internet-users. Participants were given a battery of psychological tests to explore levels of internet addiction, mood, anxiety, depression, schizotypy, and autism traits. They were then given exposure to the internet for 15 min, and re-tested for mood and current anxiety. Internet addiction was associated with long-standing depression, impulsive nonconformity, and autism traits. High internet-users also showed a pronounced decrease in mood following internet use compared to the low internet-users. The immediate negative impact of exposure to the internet on the mood of internet addicts may contribute to increased usage by those individuals attempting to reduce their low mood by re-engaging rapidly in internet use.

Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect

International Nuclear Information System (INIS)

Gerecke, Donald R.; Chen Minjun; Isukapalli, Sastry S.; Gordon, Marion K.; Chang, Y.-C.; Tong Weida; Androulakis, Ioannis P.; Georgopoulos, Panos G.

2009-01-01

Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal-epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine-cytokine receptor interaction, cell adhesion molecules (CAMs), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysis to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor I, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors

Intuitive Understanding of Solutions of Partially Differential Equations

Science.gov (United States)

Kobayashi, Y.

2008-01-01

This article uses diagrams that help the observer see how solutions of the wave equation and heat conduction equation are obtained. The analytical approach cannot necessarily show the mechanisms of the key to the solution without transforming the differential equation into a more convenient form by separation of variables. The visual clues based…

Disruption of apoptosis pathways involved in zebrafish gonad differentiation by 17α-ethinylestradiol and fadrozole exposures

International Nuclear Information System (INIS)

Luzio, Ana; Matos, Manuela; Santos, Dércia; Fontaínhas-Fernandes, António A.; Monteiro, Sandra M.

2016-01-01

Highlights: • Apoptosis in females is avoided by anti-apoptotic pathways and in males is essential to the “juvenile ovary” failure. • BIRC5 is central to the regulation of zebrafish spermatogenesis. • EE2 did not change sex ratios, but Fadrozole induced masculinization with a significant increase in male proportion. • The few females identified after exposure to Fadrozole may have avoided sex reversal by increasing anti-apoptotic proteins. • EE2 increased the pro-apoptotic genes/proteins in males, promoting gonad differentiation. - Abstract: Zebrafish (Danio rerio) sex determination seems to involve genetic factors (GSD) but also environmental factors (ESD), such as endocrine disrupting chemicals (EDCs) that are known to mimic endogenous hormones and disrupt gonad differentiation. Apoptosis has also been proposed to play a crucial role in zebrafish gonad differentiation. Nevertheless, the interactions between EDCs and apoptosis have received little attention. Thus, this study aimed to assess if and which apoptotic pathways are involved in zebrafish gonad differentiation and how EDCs may interfere with this process. With these purposes, zebrafish were exposed to 17α-ethinylestradiol (EE_2, 4 ng/L) and fadrozole (Fad, 50 μg/L) from 2 h to 35 days post-fertilization (dpf). Afterwards, a gene expression analysis by qRT-PCR and a stereological analysis, based on systematic sampling and protein immunohistochemistry, were performed. The death receptors (FAS; TRADD), anti-apoptotic (BCL-2; MDM2), pro-apoptotic (CASP-2 and −6) and cell proliferation (BIRC5/survivin; JUN) genes and proteins were evaluated. In general, apoptosis was inhibited in females through the involvement of anti-apoptotic pathways, while in males apoptosis seemed to be crucial to the failure of the “juvenile ovary” development and the induction of testes transformation. The JUN protein was shown to be necessary in juvenile ovaries, while the BIRC5 protein seemed to be involved in

Disruption of apoptosis pathways involved in zebrafish gonad differentiation by 17α-ethinylestradiol and fadrozole exposures

Energy Technology Data Exchange (ETDEWEB)

Luzio, Ana, E-mail: aluzio@utad.pt [Centre for the Research and Technology of Agro-Environmental and Biological Sciences, CITAB, Departamento de Biologia e Ambiente (DeBA), University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); Life Sciences and Environment School, University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); Matos, Manuela [University of Lisbon, Faculty of Sciences, BioISI– Biosystems & Integrative Sciences Institute, Campo Grande, 1749-016 Lisbon (Portugal); Department of Genetics and Biotechnology, Life Sciences and Environment School (ECVA), University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); Santos, Dércia [Life Sciences and Environment School, University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); Fontaínhas-Fernandes, António A.; Monteiro, Sandra M. [Centre for the Research and Technology of Agro-Environmental and Biological Sciences, CITAB, Departamento de Biologia e Ambiente (DeBA), University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); Life Sciences and Environment School, University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); and others

2016-08-15

Highlights: • Apoptosis in females is avoided by anti-apoptotic pathways and in males is essential to the “juvenile ovary” failure. • BIRC5 is central to the regulation of zebrafish spermatogenesis. • EE2 did not change sex ratios, but Fadrozole induced masculinization with a significant increase in male proportion. • The few females identified after exposure to Fadrozole may have avoided sex reversal by increasing anti-apoptotic proteins. • EE2 increased the pro-apoptotic genes/proteins in males, promoting gonad differentiation. - Abstract: Zebrafish (Danio rerio) sex determination seems to involve genetic factors (GSD) but also environmental factors (ESD), such as endocrine disrupting chemicals (EDCs) that are known to mimic endogenous hormones and disrupt gonad differentiation. Apoptosis has also been proposed to play a crucial role in zebrafish gonad differentiation. Nevertheless, the interactions between EDCs and apoptosis have received little attention. Thus, this study aimed to assess if and which apoptotic pathways are involved in zebrafish gonad differentiation and how EDCs may interfere with this process. With these purposes, zebrafish were exposed to 17α-ethinylestradiol (EE{sub 2}, 4 ng/L) and fadrozole (Fad, 50 μg/L) from 2 h to 35 days post-fertilization (dpf). Afterwards, a gene expression analysis by qRT-PCR and a stereological analysis, based on systematic sampling and protein immunohistochemistry, were performed. The death receptors (FAS; TRADD), anti-apoptotic (BCL-2; MDM2), pro-apoptotic (CASP-2 and −6) and cell proliferation (BIRC5/survivin; JUN) genes and proteins were evaluated. In general, apoptosis was inhibited in females through the involvement of anti-apoptotic pathways, while in males apoptosis seemed to be crucial to the failure of the “juvenile ovary” development and the induction of testes transformation. The JUN protein was shown to be necessary in juvenile ovaries, while the BIRC5 protein seemed to be involved

Differential Psychological Impact of Internet Exposure on Internet Addicts

OpenAIRE

Romano, Michela; Osborne, Lisa A.; Truzoli, Roberto; Reed, Phil

2013-01-01

The study explored the immediate impact of internet exposure on the mood and psychological states of internet addicts and low internet-users. Participants were given a battery of psychological tests to explore levels of internet addiction, mood, anxiety, depression, schizotypy, and autism traits. They were then given exposure to the internet for 15 min, and re-tested for mood and current anxiety. Internet addiction was associated with long-standing depression, impulsive nonconformity, and aut...

Structurally distinct polycyclic aromatic hydrocarbons induce differential transcriptional responses in developing zebrafish

International Nuclear Information System (INIS)

Goodale, Britton C.; Tilton, Susan C.; Corvi, Margaret M.; Wilson, Glenn R.; Janszen, Derek B.; Anderson, Kim A.; Waters, Katrina M.; Tanguay, Robert L.

2013-01-01

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. These multi-ring chemicals differentially activate the aryl hydrocarbon receptor (AHR) in a structurally dependent manner, and induce toxicity via both AHR-dependent and -independent mechanisms. PAH exposure is known to induce developmental malformations in zebrafish embryos, and recent studies have shown cardiac toxicity induced by compounds with low AHR affinity. Unraveling the potentially diverse molecular mechanisms of PAH toxicity is essential for understanding the hazard posed by complex PAH mixtures present in the environment. We analyzed transcriptional responses to PAH exposure in zebrafish embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR) at concentrations that induced developmental malformations by 120 h post-fertilization (hpf). Whole genome microarray analysis of mRNA expression at 24 and 48 hpf identified genes that were differentially regulated over time and in response to the three PAH structures. PAH body burdens were analyzed at both time points using GC–MS, and demonstrated differences in PAH uptake into the embryos. This was important for discerning dose-related differences from those that represented unique molecular mechanisms. While BAA misregulated the least number of transcripts, it caused strong induction of cyp1a and other genes known to be downstream of the AHR, which were not induced by the other two PAHs. Analysis of functional roles of misregulated genes and their predicted regulatory transcription factors also distinguished the BAA response from regulatory networks disrupted by DBT and PYR exposure. These results indicate that systems approaches can be used to classify the toxicity of PAHs based on the networks perturbed following exposure, and may provide a path for unraveling the toxicity of complex PAH mixtures. - Highlights: • Defined global mRNA expression

Conceptual Challenges of the Systemic Approach in Understanding Cell Differentiation.

Science.gov (United States)

Paldi, Andras

2018-01-01

The cells of a multicellular organism are derived from a single zygote and genetically identical. Yet, they are phenotypically very different. This difference is the result of a process commonly called cell differentiation. How the phenotypic diversity emerges during ontogenesis or regeneration is a central and intensely studied but still unresolved issue in biology. Cell biology is facing conceptual challenges that are frequently confused with methodological difficulties. How to define a cell type? What stability or change means in the context of cell differentiation and how to deal with the ubiquitous molecular variations seen in the living cells? What are the driving forces of the change? We propose to reframe the problem of cell differentiation in a systemic way by incorporating different theoretical approaches. The new conceptual framework is able to capture the insights made at different levels of cellular organization and considered previously as contradictory. It also provides a formal strategy for further experimental studies.

Contribution of non integer integro-differential operators (NIDO) to the geometrical understanding of Riemann's conjecture-(II)

International Nuclear Information System (INIS)

Le Mehaute, Alain; El Kaabouchi, Abdelaziz; Nivanen, Laurent

2008-01-01

Advances in fractional analysis suggest a new way for the physics understanding of Riemann's conjecture. It asserts that, if s is a complex number, the non trivial zeros of zeta function 1/(ζ(s)) =Σ n=1 ∞ (μ(n))/(n s ) in the gap [0, 1], is characterized by s=1/2 (1+2iθ). This conjecture can be understood as a consequence of 1/2-order fractional differential characteristics of automorph dynamics upon opened punctuated torus with an angle at infinity equal to π/4. This physical interpretation suggests new opportunities for revisiting the cryptographic methodologies

The biology of human psychosexual differentiation.

Science.gov (United States)

Gooren, Louis

2006-11-01

Most attempts to identify biological underpinnings of gender identity and sexual orientation in humans have investigated effects of sex steroids, so pivotal in the differentiation of the genitalia, showing strong parallels between animals and the human. The information on humans is derived from the so-called 'experiments of nature', clinical entities with a lesser-than-normal androgen exposure in XY subjects and a higher than normal androgen exposure in XX subjects. Prenatal androgenization appears to predispose to a male gender identity development, but apparently not decisively since 40-50% of 46,XY intersexed children with a history of prenatal androgen exposure do not develop a male gender identity. Obviously, male-to-female transsexuals, with a normal androgen exposure prenatally (there is no serious evidence to the contrary) develop a female gender identity, through unknown biological mechanisms apparently overriding the effects of prenatal androgens. The latest studies in 46, XX subjects exposed to prenatal androgens show that prenatal androgenization of 46,XX fetuses leads to marked masculinization of later gender-related behavior but does not lead to gender confusion/dysphoria. The example of female-to-male transsexuals, without evidence of prenatal androgen exposure, indicates that a male gender identity can develop without a significant androgen stimulus. So we are far away from any comprehensive understanding of hormonal imprinting on gender identity formation. Brain studies in homosexuals have not held up in replication studies or are in need of replication in transsexuals. Genetic studies and the fraternal birth order hypothesis provide indications of familial clustering of homosexuality but in many homosexuals these genetic patterns cannot be identified. The biological explanations advanced for the birth order hypothesis lack any experimental support.

Understanding and responding the students in learning mathematics through the differentiated instruction

Science.gov (United States)

Hapsari, T.; Darhim; Dahlan, J. A.

2018-05-01

This research discusses the differentiated instruction, a mathematic learning which is as expected by the students in connection with the differentiated instruction itself, its implementation, and the students’ responses. This research employs a survey method which involves 62 students as the research respondents. The mathematics learning types required by the students and their responses to the differentiated instruction are examined through questionnaire and interview. The mathematics learning types in orderly required by the students, from the highest frequency cover the easily understood instructions, slowly/not rushing teaching, fun, not complicated, interspersed with humour, various question practices, not too serious, and conducive class atmosphere for the instructions. Implementing the differentiated instruction is not easy. The teacher should be able to constantly assess the students, s/he should have good knowledge of relevant materials and instructions, and properly prepare the instructions, although it is time-consuming. The differentiated instruction is implemented on the instructions of numerical pattern materials. The strategies implemented are flexible grouping, tiered assignment, and compacting. The students positively respond the differentiated learning instruction that they become more motivated and involved in the instruction.

Exposure to early adversity: Points of cross-species translation that can lead to improved understanding of depression.

Science.gov (United States)

Andersen, Susan L

2015-05-01

The relationship between developmental exposure to adversity and affective disorders is reviewed. Adversity discussed herein includes physical and sexual abuse, neglect, or loss of a caregiver in humans. While these stressors can occur at any point during development, the unique temporal relationship to specific depressive symptoms was the focus of discussion. Further influences of stress exposure during sensitive periods can vary by gender and duration of abuse as well. Data from animal studies are presented to provide greater translational and causal understanding of how sensitive periods, different types of psychosocial stressors, and sex interact to produce depressive-like behaviors. Findings from maternal separation, isolation rearing, chronic variable stress, and peer-peer rearing paradigms clarify interpretation about how various depressive behaviors are influenced by age of exposure. Depressive behaviors are broken down into the following categories: mood and affect, anhedonia, energy, working memory, sleep-wake, appetite changes, suicide, and general malaise. Cross-species evidence from humans, nonhuman primates, rats, and mice within each of these categories is discussed. In conclusion, sensitive periods for affective-related behaviors (anxiety, mood, and controllability) occur earlier in life, while other aspects of depression are associated with adversity later during adolescence.

Early prenatal androgen exposure reduces testes size and sperm concentration in sheep without altering neuroendocrine differentiation and masculine sexual behavior.

Science.gov (United States)

Scully, C M; Estill, C T; Amodei, R; McKune, A; Gribbin, K P; Meaker, M; Stormshak, F; Roselli, C E

2018-01-01

Prenatal androgens are largely responsible for growth and differentiation of the genital tract and testis and for organization of the control mechanisms regulating male reproductive physiology and behavior. The aim of the present study was to evaluate the impact of inappropriate exposure to excess testosterone (T) during the first trimester of fetal development on the reproductive function, sexual behavior, and fertility potential of rams. We found that biweekly maternal T propionate (100 mg) treatment administered from Day 30-58 of gestation significantly decreased (P < 0.05) postpubertal scrotal circumference and sperm concentration. Prenatal T exposure did not alter ejaculate volume, sperm motility and morphology or testis morphology. There was, however, a trend for more T-exposed rams than controls to be classified as unsatisfactory potential breeders during breeding soundness examinations. Postnatal serum T concentrations were not affected by prenatal T exposure, nor was the expression of key testicular genes essential for spermatogenesis and steroidogenesis. Basal serum LH did not differ between treatment groups, nor did pituitary responsiveness to GnRH. T-exposed rams, like control males, exhibited vigorous libido and were sexually attracted to estrous females. In summary, these results suggest that exposure to exogenous T during the first trimester of gestation can negatively impact spermatogenesis and compromise the reproductive fitness of rams. Copyright © 2017 Elsevier Inc. All rights reserved.

Understanding the relationship between repetition priming and mere exposure.

Science.gov (United States)

Butler, Laurie T; Berry, Dianne C

2004-11-01

Over the last two decades interest in implicit memory, most notably repetition priming, has grown considerably. During the same period, research has also focused on the mere exposure effect. Although the two areas have developed relatively independently, a number of studies has described the mere exposure effect as an example of implicit memory. Tacit in their comparisons is the assumption that the effect is more specifically a demonstration of repetition priming. Having noted that this assumption has attracted relatively little attention, this paper reviews current evidence and shows that it is by no means conclusive. Although some evidence is suggestive of a common underlying mechanism, even a modified repetition priming (perceptual fluency/attribution) framework cannot accommodate all of the differences between the two phenomena. Notwithstanding this, it seems likely that a version of this theoretical framework still offers the best hope of a comprehensive explanation for the mere exposure effect and its relationship to repetition priming. As such, the paper finishes by offering some initial guidance as to ways in which the perceptual fluency/attribution framework might be extended, as well as outlining important areas for future research.

Differential Immunotoxicity Induced by Two Different Windows of Developmental Trichloroethylene Exposure

Directory of Open Access Journals (Sweden)

Kathleen M. Gilbert

2014-01-01

Full Text Available Developmental exposure to environmental toxicants may induce immune system alterations that contribute to adult stage autoimmune disease. We have shown that continuous exposure of MRL+/+ mice to trichloroethylene (TCE from gestational day (GD 0 to postnatal day (PND 49 alters several aspects of CD4+ T cell function. This window of exposure corresponds to conception-adolescence/young adulthood in humans. More narrowly defining the window of TCE developmental exposure causes immunotoxicity that would establish the stage at which avoidance and/or intervention would be most effective. The current study divided continuous TCE exposure into two separate windows, namely, gestation only (GD0 to birth (PND0 and early-life only (PND0-PND49. The mice were examined for specific alterations in CD4+ T cell function at PND49. One potentially long-lasting effect of developmental exposure, alterations in retrotransposon expression indicative of epigenetic alterations, was found in peripheral CD4+ T cells from both sets of developmentally exposed mice. Interestingly, certain other effects, such as alterations in thymus cellularity, were only found in mice exposed to TCE during gestation. In contrast, expansion of memory/activation cell subset of peripheral CD4+ T cells were only found in mice exposed to TCE during early life. Different windows of developmental TCE exposure can have different functional consequences.

The influence of high intensity terahertz radiation on mammalian cell adhesion, proliferation and differentiation.

Science.gov (United States)

Williams, Rachel; Schofield, Amy; Holder, Gareth; Downes, Joan; Edgar, David; Harrison, Paul; Siggel-King, Michele; Surman, Mark; Dunning, David; Hill, Stephen; Holder, David; Jackson, Frank; Jones, James; McKenzie, Julian; Saveliev, Yuri; Thomsen, Neil; Williams, Peter; Weightman, Peter

2013-01-21

Understanding the influence of exposure of biological systems to THz radiation is becoming increasingly important. There is some evidence to suggest that THz radiation can influence important activities within mammalian cells. This study evaluated the influence of the high peak power, low average power THz radiation produced by the ALICE (Daresbury Laboratory, UK) synchrotron source on human epithelial and embryonic stem cells. The cells were maintained under standard tissue culture conditions, during which the THz radiation was delivered directly into the incubator for various exposure times. The influence of the THz radiation on cell morphology, attachment, proliferation and differentiation was evaluated. The study demonstrated that there was no difference in any of these parameters between irradiated and control cell cultures. It is suggested that under these conditions the cells are capable of compensating for any effects caused by exposure to THz radiation with the peak powers levels employed in these studies.

Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation

Directory of Open Access Journals (Sweden)

Mary Prahl

2016-10-01

Full Text Available Abstract Background In malaria-endemic areas, the first exposure to malaria antigens often occurs in utero when the fetal immune system is poised towards the development of tolerance. Children exposed to placental malaria have an increased risk of clinical malaria in the first few years of life compared to unexposed children. Recent work has suggested the potential of pregnancy-associated malaria to induce immune tolerance in children living in malaria-endemic areas. A study was completed to evaluate the effect of malaria exposure during pregnancy on fetal immune tolerance and effector responses. Methods Using cord blood samples from a cohort of mother-infant pairs followed from early in pregnancy until delivery, flow cytometry analysis was completed to assess the relationship between pregnancy-associated malaria and fetal cord blood CD4 and dendritic cell phenotypes. Results Cord blood FoxP3+ Treg counts were higher in infants born to mothers with Plasmodium parasitaemia early in pregnancy (12–20 weeks of gestation; p = 0.048, but there was no association between Treg counts and the presence of parasites in the placenta at the time of delivery (by loop-mediated isothermal amplification (LAMP; p = 0.810. In contrast, higher frequencies of activated CD4 T cells (CD25+FoxP3−CD127+ were observed in the cord blood of neonates with active placental Plasmodium infection at the time of delivery (p = 0.035. This population exhibited evidence of effector memory differentiation, suggesting priming of effector T cells in utero. Lastly, myeloid dendritic cells were higher in the cord blood of infants with histopathologic evidence of placental malaria (p < 0.0001. Conclusion Together, these data indicate that in utero exposure to malaria drives expansion of both regulatory and effector T cells in the fetus, and that the timing of this exposure has a pivotal role in determining the polarization of the fetal immune response.

Minority and Immigrant Youth Exposure to Community Violence: The Differential Effects of Family Management and Peers.

Science.gov (United States)

Antunes, Maria João Lobo; Ahlin, Eileen M

2018-02-01

Experiences with neighborhood violence can produce negative consequences in youth, including stress, anxiety, and deviant behavior. Studies report that immigrant and minority youth are more likely to be exposed to violence but less likely to perpetrate it. Similarly, research shows parenting practices are differentially adopted by Blacks, Whites, and Hispanics. Although family management strategies can often act as a barrier to the detrimental effects of exposure to community violence (ETV-C), there is a paucity of investigation on how Hispanic subgroups (e.g., Puerto Rican, Mexican) and immigrant families employ such practices in protecting their children against victimization and violence in the community. Applying an ecological framework, we use data from the Project on Human Development in Chicago Neighborhoods to examine the role of parenting and peer relationships on youth ETV-C, across race/ethnicity and immigrant generational status. Our sample is drawn from Cohorts 9, 12, and 15, and is over 40% Hispanic-Latino. We investigate the differences in within and outside the home family management strategies in terms of both race/ethnicity and immigrant generational status. Our work also seeks to determine the effects of race/ethnicity and immigrant status on youth ETV-C, while examining the influence of family management and peer relations. Results indicate that the adoption of family management practices is not homogeneous across Hispanic subgroups or immigrant generational status, and parenting practices seem to mediate the relationship between these characteristics and exposure to violence. Variations in parenting practices underscore the need to disentangle the cultural plurality of racial/ethnic grouping and how immigrant generational status influences parenting choices that protect children from exposure to violence in the community.

Osteoblastic cells: differentiation and trans-differentiation

DEFF Research Database (Denmark)

Kassem, Moustapha; Abdallah, Basem; Saeed, Hamid

2008-01-01

The osteoblast is the bone forming cell and is derived from mesenchymal stem cells (MSC) present among the bone marrow stroma. MSC are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts and adipocytes. Understanding the mechanisms underlying osteoblast different...

Prenatal exposure to anticonvulsants and psychosexual development

NARCIS (Netherlands)

Dessens, A. B.; Cohen-Kettenis, P. T.; Mellenbergh, G. J.; vd Poll, N.; Koppe, J. G.; Boer, K.

1999-01-01

Animal studies have shown that prenatal exposure to the anticonvulsant drugs phenobarbital and phenytoin alters steroid hormone levels which consequently leads to disturbed sexual differentiation. In this study, possible sequelae of prenatal exposure to these anticonvulsants on gender development in

Differential Rationality and Personal Development.

Science.gov (United States)

Fincher, Cameron

This publication discusses differential rationality; it asserts that the development of institutions, professions, and individuals involves the differentiation of forms and styles of thinking and knowing that are, in various ways, idiosyncratic. Based on this understanding, differential rationality can be seen as a developmental construct that…

Repeated morphine treatment influences operant and spatial learning differentially

Institute of Scientific and Technical Information of China (English)

Mei-Na WANG; Zhi-Fang DONG; Jun CAO; Lin XU

2006-01-01

Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning.Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.

The role of socioeconomic factors in Black-White health inequities across the life course: Point-in-time measures, long-term exposures, and differential health returns.

Science.gov (United States)

Boen, Courtney

2016-12-01

Research links Black-White health disparities to racial differences in socioeconomic status (SES), but understanding of the role of SES in racial health gaps has been restricted by reliance on static measures of health and socioeconomic well-being that mask the dynamic quality of these processes and ignore the racialized nature of the SES-health connection. Utilizing twenty-three years of longitudinal data from the Panel Study of Income Dynamics (1984-2007), this study uses multilevel growth curve models to examine how multiple dimensions of socioeconomic well-being-including long-term economic history and differential returns to SES-contribute to the life course patterning of Black-White health disparities across two critical markers of well-being: body mass index (N = 9057) and self-rated health (N = 11,329). Findings indicate that long-term SES exerts a significant influence on both body mass index and self-rated health, net of point-in-time measures, and that Black-White health gaps are smallest in models that adjust for both long-term and current SES. I also find that Blacks and Whites receive differential health returns to increases in SES, which suggests that other factors-such as neighborhood segregation and exposure racial discrimination-may restrict Blacks from converting increases in SES into health improvements in the same way as Whites. Together, these processes contribute to the life course patterning of Black-White health gaps and raise concerns about previous misestimation of the role of SES in racial health disparities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prenatal exposure of mice to diethylstilbestrol disrupts T-cell differentiation by regulating Fas/Fas ligand expression through estrogen receptor element and nuclear factor-κB motifs.

Science.gov (United States)

Singh, Narendra P; Singh, Udai P; Nagarkatti, Prakash S; Nagarkatti, Mitzi

2012-11-01

Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effect of prenatal exposure to DES on thymocyte differentiation involving apoptotic pathways. Prenatal DES exposure caused thymic atrophy, apoptosis, and up-regulation of Fas and Fas ligand (FasL) expression in thymocytes. To examine the mechanism underlying DES-mediated regulation of Fas and FasL, we performed luciferase assays using T cells transfected with luciferase reporter constructs containing full-length Fas or FasL promoters. There was significant luciferase induction in the presence of Fas or FasL promoters after DES exposure. Further analysis demonstrated the presence of several cis-regulatory motifs on both Fas and FasL promoters. When DES-induced transcription factors were analyzed, estrogen receptor element (ERE), nuclear factor κB (NF-κB), nuclear factor of activated T cells (NF-AT), and activator protein-1 motifs on the Fas promoter, as well as ERE, NF-κB, and NF-AT motifs on the FasL promoter, showed binding affinity with the transcription factors. Electrophoretic mobility-shift assays were performed to verify the binding affinity of cis-regulatory motifs of Fas or FasL promoters with transcription factors. There was shift in mobility of probes (ERE or NF-κB2) of both Fas and FasL in the presence of nuclear proteins from DES-treated cells, and the shift was specific to DES because these probes failed to shift their mobility in the presence of nuclear proteins from vehicle-treated cells. Together, the current study demonstrates that prenatal exposure to DES triggers significant alterations in apoptotic molecules expressed on thymocytes, which may affect T-cell differentiation and cause long-term effects on the immune functions.

Effects of Long-term exposure of Gelatinated and Non-gelatinated Cadmium Telluride Quantum Dots on Differentiated PC12 cells

LENUS (Irish Health Repository)

Prasad, Babu R

2012-01-20

Abstract Background The inherent toxicity of unmodified Quantum Dots (QDs) is a major hindrance to their use in biological applications. To make them more potent as neuroprosthetic and neurotherapeutic agents, thioglycolic acid (TGA) capped CdTe QDs, were coated with a gelatine layer and investigated in this study with differentiated pheochromocytoma 12 (PC12) cells. The QD - cell interactions were investigated after incubation periods of up to 17 days by MTT and APOTOX-Glo Triplex assays along with using confocal microscopy. Results Long term exposure (up to 17 days) to gelatinated TGA-capped CdTe QDs of PC12 cells in the course of differentiation and after neurites were grown resulted in dramatically reduced cytotoxicity compared to non-gelatinated TGA-capped CdTe QDs. Conclusion The toxicity mechanism of QDs was identified as caspase-mediated apoptosis as a result of cadmium leaking from the core of QDs. It was therefore concluded that the gelatine capping on the surface of QDs acts as a barrier towards the leaking of toxic ions from the core QDs in the long term (up to 17 days).

The report of medical exposures in diagnostic radiology. Pt. 1. The questionnaire of medical exposure and standard radiation exposure

International Nuclear Information System (INIS)

Sasakawa, Yasuhiro; Matsumura, Yoshitaka; Iwasaki, Takanobu; Segawa, Hiroo; Yasuda, Sadatoshi; Kusuhara, Toshiaki

1997-01-01

We had made reports of patient radiation exposure for doctors to judge adaptation of medical radiation rightly. By these reports the doctors can be offered data of exposure dose and somatic effect. First, we sent out questionnaires so that we grasped the doctor's understanding about radiation exposure. Consequently we understood that the doctors had demanded data of exposure dose and somatic effect. Secondly, by the result of questionnaires we made the tables of exposure dose about radiological examination. As a result we have be able to presume exposure dose about high radiation sensitive organization as concrete figures. (author)

Differential effects of 5-HTTLPR genotypes on mood, memory, and attention bias following acute tryptophan depletion and stress exposure.

Science.gov (United States)

Firk, Christine; Markus, C Rob

2009-05-01

Polymorphisms of the serotonin transporter gene (5-HTTLPR) may be associated with increased vulnerability to acute tryptophan depletion (ATD) and depression vulnerability especially following stressful life events. The aim of the present study was to investigate the effects of ATD in subjects with different 5-HTTLPR profiles before and after stress exposure on affective and cognitive-attentional changes. Eighteen subjects with homozygotic short alleles (S'/S') and 17 subjects with homozygotic long alleles (L'/L') of the 5-HTTLPR participated in a double-blind, placebo-controlled, crossover design to measure the effects of ATD on mood, memory, and attention before and after acute stress exposure. ATD lowered mood in all subjects independent of genotype. In S'/S' genotypes, mild acute stress increased depressive mood and in L'/L' genotypes increased feelings of vigor. Furthermore, S'/S' genotypes differed from L'/L' genotypes on measures of attention independent of treatment and memory following ATD. Polymorphisms of the 5-HTTLPR differentially affect responses to mild stress and ATD, suggesting greater vulnerability of S'/S' carriers to serotonergic manipulations and supporting increased depression vulnerability.

Diverse effects of lead nitrate on the proliferation, differentiation, and gene expression of stem cells isolated from a dental origin.

Science.gov (United States)

Abdullah, Mariam; Rahman, Fazliny Abd; Gnanasegaran, Nareshwaran; Govindasamy, Vijayendran; Abu Kasim, Noor Hayaty; Musa, Sabri

2014-01-01

Lead (Pb(2+)) exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb(2+) toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb(2+) concentrations (160, 80, 40, 20, and 10 µM) for 24 hours to identify the adverse effects of Pb(2+) on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb(2+) treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb(2+) continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1) and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb(2+) exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.

Diverse Effects of Lead Nitrate on the Proliferation, Differentiation, and Gene Expression of Stem Cells Isolated from a Dental Origin

Directory of Open Access Journals (Sweden)

Mariam Abdullah

2014-01-01

Full Text Available Lead (Pb2+ exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb2+ toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb2+ concentrations (160, 80, 40, 20, and 10 µM for 24 hours to identify the adverse effects of Pb2+ on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb2+ treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb2+ continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1 and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb2+ exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.

Compensating Differentials for Sexual Harassment

OpenAIRE

Joni Hersch

2011-01-01

Workplace sexual harassment is illegal, but many workers report that they have been sexually harassed. Exposure to the risk of sexual harassment may decrease productivity, which would reduce wages. Alternatively, workers may receive a compensating differential for exposure to sexual harassment, which would increase wages. Data on claims of sexual harassment filed with the Equal Employment Opportunity Commission are used to calculate the first measures of sexual harassment risks by industry, a...

Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis.

Science.gov (United States)

Yüksel, Melih; Power, Jeffrey J; Ribbe, Jan; Volkmann, Thorsten; Maier, Berenike

2016-01-01

In the stationary phase, Bacillus subtilis differentiates stochastically and transiently into the state of competence for transformation (K-state). The latter is associated with growth arrest, and it is unclear how the ability to develop competence is stably maintained, despite its cost. To quantify the effect differentiation has on the competitive fitness of B. subtilis, we characterized the competition dynamics between strains with different probabilities of entering the K-state. The relative fitness decreased with increasing differentiation probability both during the stationary phase and during outgrowth. When exposed to antibiotics inhibiting cell wall synthesis, transcription, and translation, cells that differentiated into the K-state showed a selective advantage compared to differentiation-deficient bacteria; this benefit did not require transformation. Although beneficial, the K-state was not induced by sub-MIC concentrations of antibiotics. Increasing the differentiation probability beyond the wt level did not significantly affect the competition dynamics with transient antibiotic exposure. We conclude that the competition dynamics are very sensitive to the fraction of competent cells under benign conditions but less sensitive during antibiotic exposure, supporting the picture of stochastic differentiation as a fitness trade-off.

Understanding the risk coming from the radiation exposure

International Nuclear Information System (INIS)

Pierzo, J.A.

2007-01-01

From 1972, the National Academy has published a series of reports on the biological effects of ionizing radiation (BEIR) in relation to the health effects of the low level radiation. The Environmental Protection Agency, the Department of Energy and the Academy of Sciences of US, began in 1996 the first phase of the BEIR VII report about the health risks associated to the exposure to low level ionizing radiation. The purpose of the first phase of the study is to revise the literature and to decide if enough novel information existed to guarantee the complete study. The National Academies concluded that enough information existed with an appropriate time to carry out the reanalysis. Among the conclusions of BEIR VII are that the current scientific evidence is concordant with the hypothesis of the existence of a linear model without threshold (LSU) in the dose-response relationship among the exposure to ionizing radiation and the cancer development in humans. This implies that very low dose even has the potential of causing deleterious effects in the health, although the risk to low dose is very small. (Author)

Cell cycle pathway dysregulation in human keratinocytes during chronic exposure to low arsenite.

Science.gov (United States)

Al-Eryani, Laila; Waigel, Sabine; Jala, Venkatakrishna; Jenkins, Samantha F; States, J Christopher

2017-09-15

Arsenic is naturally prevalent in the earth's crust and widely distributed in air and water. Chronic low arsenic exposure is associated with several cancers in vivo, including skin cancer, and with transformation in vitro of cell lines including immortalized human keratinocytes (HaCaT). Arsenic also is associated with cell cycle dysregulation at different exposure levels in multiple cell lines. In this work, we analyzed gene expression in HaCaT cells to gain an understanding of gene expression changes contributing to transformation at an early time point. HaCaT cells were exposed to 0 or 100nM NaAsO 2 for 7weeks. Total RNA was purified and analyzed by microarray hybridization. Differential expression with fold change≥|1.5| and p-value≤0.05 was determined using Partek Genomic Suite™ and pathway and network analyses using MetaCore™ software (FDR≤0.05). Cell cycle analysis was performed using flow cytometry. 644 mRNAs were differentially expressed. Cell cycle/cell cycle regulation pathways predominated in the list of dysregulated pathways. Genes involved in replication origin licensing were enriched in the network. Cell cycle assay analysis showed an increase in G2/M compartment in arsenite-exposed cells. Arsenite exposure induced differential gene expression indicating dysregulation of cell cycle control, which was confirmed by cell cycle analysis. The results suggest that cell cycle dysregulation is an early event in transformation manifested in cells unable to transit G2/M efficiently. Further study at later time points will reveal additional changes in gene expression related to transformation processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Exposure to field vs. storage wheat dust: different consequences on respiratory symptoms and immune response among grain workers.

Science.gov (United States)

Barrera, Coralie; Wild, Pascal; Dorribo, Victor; Savova-Bianchi, Dessislava; Laboissière, Audrey; Pralong, Jacques A; Danuser, Brigitta; Krief, Peggy; Millon, Laurence; Reboux, Gabriel; Niculita-Hirzel, Hélène

2018-05-26

The aim of this study was to understand the differential acute effects of two distinct wheat-related dusts, such as field or stored wheat dust handling, on workers' health and how those effects evolved at 6 month intervals. Exposure, work-related symptoms, changes in lung function, and blood samples of 81 workers handling wheat and 61 controls were collected during the high exposure season and 6 months after. Specific IgG, IgE, and precipitins against 12 fungi isolated from wheat dust were titrated by enzyme-linked immunosorbent assay, dissociation-enhanced lanthanide fluorescence immunoassay, and electrosyneresis. The level of fungi was determined in the workers' environment. Levels of exhaled fraction of nitrogen monoxide (F E NO) and total IgE were obtained. Exposure response associations were investigated by mixed logistic and linear regression models. The recent exposure to field wheat dust was associated with a higher prevalence for five of six self-reported airway symptoms and with a lower F E NO than those in the control population. Exposure to stored wheat dust was only associated with cough. No acute impact of exposure on respiratory function was observed. Exposure to field wheat dust led to workers' sensitization against the three field fungi Aureobasidum, Cryptococcus, and Phoma, although exposure to storage wheat dust was associated with tolerance. The level of Ig remained stable 6 months after exposure. The clinical picture of workers exposed to field or storage wheat dust differed. The systematic characterization of the aerosol microbial profile may help to understand the reasons for those differences.

Developmental exposure to trichloroethylene promotes CD4+ T cell differentiation and hyperactivity in association with oxidative stress and neurobehavioral deficits in MRL+/+ mice

International Nuclear Information System (INIS)

Blossom, Sarah J.; Doss, Jason C.; Hennings, Leah J.; Jernigan, Stefanie; Melnyk, Stepan; James, S. Jill

2008-01-01

The non adult immune system is particularly sensitive to perinatal and early life exposures to environmental toxicants. The common environmental toxicant, trichloroethylene (TCE), was shown to increase CD4+ T cell production of the proinflammatory cytokine IFN-γ following a period of prenatal and lifetime exposure in autoimmune-prone MRL+/+ mice. In the current study, MRL+/+ mice were used to further examine the impact of TCE on the immune system in the thymus and periphery. Since there is considerable cross-talk between the immune system and the brain during development, the potential relationship between TCE and neurobehavioral endpoints were also examined. MRL+/+ mice were exposed to 0.1 mg/ml TCE (∼ 31 mg/kg/day) via maternal drinking water or direct exposure via the drinking water from gestation day 1 until postnatal day (PD) 42. TCE exposure did not impact gross motor skills but instead significantly altered social behaviors and promoted aggression associated with indicators of oxidative stress in brain tissues in male mice. The immunoregulatory effects of TCE involved a redox-associated promotion of T cell differentiation in the thymus that preceded the production of proinflammatory cytokines, IL-2, TNF-α, and IFN-γ by mature CD4+ T cells. The results demonstrated that developmental and early life TCE exposure modulated immune function and may have important implications for neurodevelopmental disorders

Understanding the exposure-time effect on speckle contrast measurements for laser displays

Science.gov (United States)

Suzuki, Koji; Kubota, Shigeo

2018-02-01

To evaluate the influence of exposure time on speckle noise for laser displays, speckle contrast measurement method was developed observable at a human eye response time using a high-sensitivity camera which has a signal multiplying function. The nonlinearity of camera light sensitivity was calibrated to measure accurate speckle contrasts, and the measuring lower limit noise of speckle contrast was improved by applying spatial-frequency low pass filter to the captured images. Three commercially available laser displays were measured over a wide range of exposure times from tens of milliseconds to several seconds without adjusting the brightness of laser displays. The speckle contrast of raster-scanned mobile projector without any speckle-reduction device was nearly constant over various exposure times. On the contrary to this, in full-frame projection type laser displays equipped with a temporally-averaging speckle-reduction device, some of their speckle contrasts close to the lower limits noise were slightly increased at the shorter exposure time due to the noise. As a result, the exposure-time effect of speckle contrast could not be observed in our measurements, although it is more reasonable to think that the speckle contrasts of laser displays, which are equipped with the temporally-averaging speckle-reduction device, are dependent on the exposure time. This discrepancy may be attributed to the underestimation of temporal averaging factor. We expected that this method is useful for evaluating various laser displays and clarify the relationship between the speckle noise and the exposure time for a further verification of speckle reduction.

Is Melanoma a stem cell tumor? Identification of neurogenic proteins in trans-differentiated cells

Directory of Open Access Journals (Sweden)

Chan Linda S

2005-03-01

Full Text Available Abstract Background Although several genes and proteins have been implicated in the development of melanomas, the molecular mechanisms involved in the development of these tumors are not well understood. To gain a better understanding of the relationship between the cell growth, tumorigenesis and differentiation, we have studied a highly malignant cat melanoma cell line that trans-differentiates into neuronal cells after exposure to a feline endogenous retrovirus RD114. Methods To define the repertoire of proteins responsible for the phenotypic differences between melanoma and its counterpart trans-differentiated neuronal cells we have applied proteomics technology and compared protein profiles of the two cell types and identified differentially expressed proteins by 2D-gel electrophoresis, image analyses and mass spectrometry. Results The melanoma and trans-differentiated neuronal cells could be distinguished by the presence of distinct sets of proteins in each. Although approximately 60–70% of the expressed proteins were shared between the two cell types, twelve proteins were induced de novo after infection of melanoma cells with RD114 virus in vitro. Expression of these proteins in trans-differentiated cells was significantly associated with concomitant down regulation of growth promoting proteins and up-regulation of neurogenic proteins (p = 95% proteins expressed in trans-differentiated cells could be associated with the development, differentiation and regulation of nervous system cells. Conclusion Our results indicate that the cat melanoma cells have the ability to differentiate into distinct neuronal cell types and they express proteins that are essential for self-renewal. Since melanocytes arise from the neural crest of the embryo, we conclude that this melanoma arose from embryonic precursor stem cells. This model system provides a unique opportunity to identify domains of interactions between the expressed proteins that halt the

Differential equations a dynamical systems approach ordinary differential equations

CERN Document Server

Hubbard, John H

1991-01-01

This is a corrected third printing of the first part of the text Differential Equations: A Dynamical Systems Approach written by John Hubbard and Beverly West. The authors' main emphasis in this book is on ordinary differential equations. The book is most appropriate for upper level undergraduate and graduate students in the fields of mathematics, engineering, and applied mathematics, as well as the life sciences, physics and economics. Traditional courses on differential equations focus on techniques leading to solutions. Yet most differential equations do not admit solutions which can be written in elementary terms. The authors have taken the view that a differential equations defines functions; the object of the theory is to understand the behavior of these functions. The tools the authors use include qualitative and numerical methods besides the traditional analytic methods. The companion software, MacMath, is designed to bring these notions to life.

Using Information on Exposure to Characterizing Risks to Human Health from Concurrent Exposures to Multiple Chemicals

NARCIS (Netherlands)

Mr Price, PSP

2012-01-01

This thesis explores the concept of using exposure information to understand, organize, and manage the risks associated with cumulative exposures to chemicals (exposures to multiple chemicals from multiple sources). The issue of cumulative exposures was identified in more than 30 years ago, but in

Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

International Nuclear Information System (INIS)

Colleoni, Silvia; Galli, Cesare; Giannelli, Serena G.; Armentero, Marie-Therese; Blandini, Fabio; Broccoli, Vania; Lazzari, Giovanna

2010-01-01

In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

Energy Technology Data Exchange (ETDEWEB)

Colleoni, Silvia, E-mail: silviacolleoni@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Galli, Cesare [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Dipartimento Clinico Veterinario, Universita di Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (Italy); Giannelli, Serena G. [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Armentero, Marie-Therese; Blandini, Fabio [Laboratory of Functional Neurochemistry, Interdepartmental Research Center for Parkinson' s Disease, Neurological Institute C. Mondino, Via Mondino 2, 27100 Pavia (Italy); Broccoli, Vania, E-mail: broccoli.vania@hsr.it [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Lazzari, Giovanna, E-mail: giovannalazzari@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy)

2010-04-15

In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

Energy Technology Data Exchange (ETDEWEB)

Madden, Jill A. [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Hoyer, Patricia B. [Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States); Devine, Patrick J. [INRS—Institut Armand-Frappier Research Centre, University of Quebec, Laval, QC H7V 1B7 (Canada); Keating, Aileen F., E-mail: akeating@iastate.edu [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States)

2014-05-01

Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKT{sup Thr308} protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

International Nuclear Information System (INIS)

Madden, Jill A.; Hoyer, Patricia B.; Devine, Patrick J.; Keating, Aileen F.

2014-01-01

Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKT Thr308 protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

Understanding Vector Fields.

Science.gov (United States)

Curjel, C. R.

1990-01-01

Presented are activities that help students understand the idea of a vector field. Included are definitions, flow lines, tangential and normal components along curves, flux and work, field conservation, and differential equations. (KR)

Understanding Coral's Short-term Adaptive Ability to Changing Environment

Science.gov (United States)

Tisthammer, K.; Richmond, R. H.

2016-02-01

Corals in Maunalua Bay, Hawaii are under chronic pressures from sedimentation and terrestrial runoffs containing multiple pollutants as a result of large scale urbanization that has taken place in the last 100 years. However, some individual corals thrive despite the prolonged exposure to these environmental stressors, which suggests that these individuals may have adapted to withstand such stressors. A recent survey showed that the lobe coral Porites lobata from the `high-stress' nearshore site had an elevated level of stress ixnduced proteins, compared to those from the `low-stress,' less polluted offshore site. To understand the genetic basis for the observed differential stress responses between the nearshore and offshore P. lobata populations, an analysis of the lineage-scale population genetic structure, as well as a reciprocal transplant experiment were conducted. The result of the genetic analysis revealed a clear genetic differentiation between P. lobata from the nearshore site and the offshore site. Following the 30- day reciprocal transplant experiment, protein expression profiles and other stress-related physiological characteristics were compared between the two populations. The experimental results suggest that the nearshore genotype can cope better with sedimentation/pollutants than the offshore genotype. This indicates that the observed genetic differentiation is due to selection for tolerance to these environmental stressors. Understanding the little-known, linage-scale genetic variation in corals offers a critical insight into their short-term adaptive ability, which is indispensable for protecting corals from impending environmental and climate change. The results of this study also offer a valuable tool for resource managers to make effective decisions on coral reef conservation, such as designing marine protected areas that incorporate and maintain such genetic diversity, and establishing acceptable pollution run-off levels.

Chronic schistosomiasis during pregnancy epigenetically reprograms T-cell differentiation in offspring of infected mothers.

Science.gov (United States)

Klar, Kathrin; Perchermeier, Sophie; Bhattacharjee, Sonakshi; Harb, Hani; Adler, Thure; Istvanffy, Rouzanna; Loffredo-Verde, Eva; Oostendorp, Robert A; Renz, Harald; Prazeres da Costa, Clarissa

2017-05-01

Schistosomiasis is a nontransplacental helminth infection. Chronic infection during pregnancy suppresses allergic airway responses in offspring. We addressed the question whether in utero exposure to chronic schistosome infection (Reg phase) in mice affects B-cell and T-cell development. Therefore, we focused our analyses on T-cell differentiation capacity induced by epigenetic changes in promoter regions of signature cytokines in offspring. Here, we show that naïve T cells from offspring of schistosome infected female mice had a strong capacity to differentiate into T H 1 cells, whereas T H 2 differentiation was impaired. In accordance, reduced levels of histone acetylation of the IL-4 promoter regions were observed in naïve T cells. To conclude, our mouse model revealed distinct epigenetic changes within the naïve T-cell compartment affecting T H 2 and T H 1 cell differentiation in offspring of mothers with chronic helminth infection. These findings could eventually help understand how helminths alter T-cell driven immune responses induced by allergens, bacterial or viral infections, as well as vaccines. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wired on steroids: sexual differentiation of the brain and its role in the expression of sexual partner preferences.

Science.gov (United States)

Alexander, Brenda M; Skinner, Donal C; Roselli, Charles E

2011-01-01

The preference to seek out a sexual partner of the opposite sex is robust and ensures reproduction and survival of the species. Development of female-directed partner preference in the male is dependent on exposure of the developing brain to gonadal steroids synthesized during critical periods of sexual differentiation of the central nervous system. In the absence of androgen exposure, a male-directed partner preference develops. The development and expression of sexual partner preference has been extensively studied in rat, ferret, and sheep model systems. From these models it is clear that gonadal testosterone, often through estrogenic metabolites, cause both masculinization and defeminization of behavior during critical periods of brain development. Changes in the steroid environment during these critical periods result in atypical sexual partner preference. In this manuscript, we review the major findings which support the hypothesis that the organizational actions of sex steroids are responsible for sexual differentiation of sexual partner preferences in select non-human species. We also explore how this information has helped to frame our understanding of the biological influences on human sexual orientation and gender identity.

New insights into virulence mechanisms of rice pathogen Acidovorax avenae subsp. avenae strain RS-1 following exposure to ß-lactam antibiotics.

Science.gov (United States)

Li, Bin; Ge, Mengyu; Zhang, Yang; Wang, Li; Ibrahim, Muhammad; Wang, Yanli; Sun, Guochang; Chen, Gongyou

2016-02-26

Recent research has shown that pathogen virulence can be altered by exposure to antibiotics, even when the growth rate is unaffected. Investigating this phenomenon provides new insights into understanding the virulence mechanisms of bacterial pathogens. This study investigates the phenotypic and transcriptomic responses of the rice pathogenic bacterium Acidovorax avenae subsp. avenae (Aaa) strain RS-1 to ß-lactam antibiotics especially Ampicillin (Amp). Our results indicate that exposure to Amp does not influence bacterial growth and biofilm formation, but alters the virulence, colonization capacity, composition of extracellular polymeric substances and secretion of Type VI secretion system (T6SS) effector Hcp. This attenuation in virulence is linked to unique or differential expression of known virulence-associated genes based on genome-wide transcriptomic analysis. The reliability of expression data generated by RNA-Seq was verified with quantitative real-time PCR of 21 selected T6SS genes, where significant down-regulation in expression of hcp gene, corresponding to the reduction in secretion of Hcp, was observed under exposure to Amp. Hcp is highlighted as a potential target for Amp, with similar changes observed in virulence-associated phenotypes between exposure to Amp and mutation of hcp gene. In addition, Hcp secretion is reduced in knockout mutants of 4 differentially expressed T6SS genes.

Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

Science.gov (United States)

Galanter, Joshua M; Gignoux, Christopher R; Oh, Sam S; Torgerson, Dara; Pino-Yanes, Maria; Thakur, Neeta; Eng, Celeste; Hu, Donglei; Huntsman, Scott; Farber, Harold J; Avila, Pedro C; Brigino-Buenaventura, Emerita; LeNoir, Michael A; Meade, Kelly; Serebrisky, Denise; Rodríguez-Cintrón, William; Kumar, Rajesh; Rodríguez-Santana, Jose R; Seibold, Max A; Borrell, Luisa N; Burchard, Esteban G; Zaitlen, Noah

2017-01-01

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10-64) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation. DOI: http://dx.doi.org/10.7554/eLife.20532.001 PMID:28044981

Exposure to suicide and suicidality in Korea: differential effects across men and women?

Science.gov (United States)

Lee, Min-Ah; Kim, Seokho; Shim, Eun-Jung

2013-05-01

Little is known about whether exposure to suicide within close social networks is associated with the suicidality in exposed individuals, and potential gender differences regarding this association. This study examines the effect of exposure to suicide on the suicidality in exposed individuals. The data were drawn from the 2009 Korean General Social Survey, a nationally representative interview survey. Suicidality was measured by the suicidality module in the Mini International Neuropsychiatric Interview (MINI), with exposure to suicide being determined by asking about the experience of a failed or completed suicide attempt by a closely related person. Exposure to the suicide of someone close was significantly associated with higher suicidality in exposed individuals. While the effect of a failed attempt became non-significant after controlling for psychological factors, that of exposure to a completed act of suicide remained significant. A subsample analysis by gender indicated a significant gender difference: with control for demographic and psychological factors, exposure to a completed suicide had a significant effect on the suicidality of females only. The effect of exposure to a failed attempt became non-significant both in males and females after controlling for other factors. Findings suggest the necessity of screening for prior exposure to suicide in suicide risk assessment and the need for gender-tailored suicide-prevention strategies.

On Degenerate Partial Differential Equations

OpenAIRE

Chen, Gui-Qiang G.

2010-01-01

Some of recent developments, including recent results, ideas, techniques, and approaches, in the study of degenerate partial differential equations are surveyed and analyzed. Several examples of nonlinear degenerate, even mixed, partial differential equations, are presented, which arise naturally in some longstanding, fundamental problems in fluid mechanics and differential geometry. The solution to these fundamental problems greatly requires a deep understanding of nonlinear degenerate parti...

Nonstandard Topics for Student Presentations in Differential Equations

Science.gov (United States)

LeMasurier, Michelle

2006-01-01

An interesting and effective way to showcase the wide variety of fields to which differential equations can be applied is to have students give short oral presentations on a specific application. These talks, which have been presented by 30-40 students per year in our differential equations classes, provide exposure to a diverse array of topics…

Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure

Energy Technology Data Exchange (ETDEWEB)

Gennaro, G. de; Longobardi, F.; Stallone, G.; Trizio, L.; Tutino, M. [University of Bari Aldo Moro, Department of Chemistry, Bari (Italy); Dragonieri, S. [University of Bari Aldo Moro, Department of Pulmonology, Bari (Italy); Musti, M. [University of Bari Aldo Moro, Department of Occupational Medicine, Bari (Italy)

2010-12-15

Malignant pleural mesothelioma (MPM) is an aggressive tumour whose main aetiology is the long-term exposure to asbestos fibres. The diagnostic procedure of MPM is difficult and often requires invasive approaches; therefore, it is clinically important to find accurate markers for MPM by new noninvasive methods that may facilitate the diagnostic process and identify patients at an earlier stage. In the present study, the exhaled breath of 13 patients with histology-established diagnosis of MPM, 13 subjects with long-term certified professional exposure to asbestos (EXP) and 13 healthy subjects without exposure to asbestos (healthy controls, HC) were analysed. An analytical procedure to determine volatile organic compounds by sampling of air on a bed of solid sorbent and thermal desorption GC-MS analysis was developed in order to identify the compounds capable of discriminating among the three groups. The application of univariate (ANOVA) and multivariate statistical treatments (PCA, DFA and CP-ANN) showed that cyclopentane and cyclohexane were the dominant variables able to discriminate among the three groups. In particular, it was found that cyclohexane is the only compound able to differentiate the MPM group from the other two; therefore, it can be a possible marker of MPM. Cyclopentane is the dominant compound in the discrimination between EXP and the other groups (MPM and HC); then, it can be considered a good indicator for long-term asbestos exposure. This result suggests the need to perform frequent and thorough investigations on people exposed to asbestos in order to constantly monitor their state of health or possibly to study the evolution of disease over time. (orig.)

Exposure of Human CD8+ T Cells to Type-2 Cytokines Impairs Division and Differentiation and Induces Limited Polarization

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Annette Fox

2018-05-01

Full Text Available Effector CD8+ T cells generally produce type-1 cytokines and mediators of the perforin/granzyme cytolytic pathway, yet type-2-polarized CD8+ cells (Tc2 are detected in type-2 (T2 cytokine-driven diseases such as asthma. It is unclear whether T2 cytokine exposure during activation is sufficient to polarize human CD8+ T cells. To address this question, a protocol was developed for high-efficiency activation of human CD8+ T cells in which purified single cells or populations were stimulated with plate-bound anti-CD3 and anti-CD11a mAb for up to 8 days in T2 polarizing or neutral conditions, before functional analysis. Activation of CD8+ naïve T cells (TN in T2 compared with neutral conditions decreased the size of single-cell clones, although early division kinetics were equivalent, indicating an effect on overall division number. Activation of TN in T2 conditions followed by brief anti-CD3 mAb restimulation favored expression of T2 cytokines, GATA3 and Eomes, and lowered expression of type-1 cytokines, Prf1, Gzmb, T-BET, and Prdm1. However, IL-4 was only weakly expressed, and PMA and ionomycin restimulation favored IFN-γ over IL-4 expression. Activation of TN in T2 compared with neutral conditions prevented downregulation of costimulatory (CD27, CD28 and lymph-node homing receptors (CCR7 and CD95 acquisition, which typically occur during differentiation into effector phenotypes. CD3 was rapidly and substantially induced after activation in neutral, but not T2 conditions, potentially contributing to greater division and differentiation in neutral conditions. CD8+ central memory T cells (TCM were less able to enter division upon reactivation in T2 compared with neutral conditions, and were more refractory to modulating IFN-γ and IL-4 production than CD8+ TN. In summary, while activation of TN in T2 conditions can generate T2 cytokine-biased cells, IL-4 expression is weak, T2 bias is lost upon strong restimulation, differentiation, and division

Noggin and Wnt3a enable BMP4-dependent differentiation of telencephalic stem cells into GluR-agonist responsive neurons

DEFF Research Database (Denmark)

Andersson, Therese; Duckworth, Joshua K; Fritz, Nicolas

2011-01-01

levels, that in turn exerted a concentration-dependent inhibition of BMP4-mediated mesenchymal differentiation of NSCs. Instead, BMP4 exposure of NSCs induced neuronal differentiation in mesenchyme-preventing conditions, whereas treatment with recombinant noggin alone did not. Wnt signaling is known...... to be essential for the development of neurons derived from the dorsal telencephalon, and co-stimulation of NSCs with BMP4+Wnt3a resulted in a synergistic effect yielding significantly increased number of mature neurons compared to stimulation with each factor alone. Thus whereas only a subset of BMP4-induced...... neurons derived from telencephalic NSCs, responded to glutamate receptor (GluR) agonists, over 80% of BMP4+Wnt3a-induced neurons responded appropriately to GluR-agonists. Our results increase the understanding of the role for BMP4 in differentiation of telencephalic multipotent progenitors, and reveal...

Increased proliferation of late-born retinal progenitor cells by gestational lead exposure delays rod and bipolar cell differentiation.

Science.gov (United States)

Chaney, Shawnta Y; Mukherjee, Shradha; Giddabasappa, Anand; Rueda, Elda M; Hamilton, W Ryan; Johnson, Jerry E; Fox, Donald A

2016-01-01

Studies of neuronal development in the retina often examine the stages of proliferation, differentiation, and synaptic development, albeit independently. Our goal was to determine if a known neurotoxicant insult to a population of retinal progenitor cells (RPCs) would affect their eventual differentiation and synaptic development. To that end, we used our previously published human equivalent murine model of low-level gestational lead exposure (GLE). Children and animals with GLE exhibit increased scotopic electroretinogram a- and b-waves. Adult mice with GLE exhibit an increased number of late-born RPCs, a prolonged period of RPC proliferation, and an increased number of late-born rod photoreceptors and rod and cone bipolar cells (BCs), with no change in the number of late-born Müller glial cells or early-born neurons. The specific aims of this study were to determine whether increased and prolonged RPC proliferation alters the spatiotemporal differentiation and synaptic development of rods and BCs in early postnatal GLE retinas compared to control retinas. C57BL/6N mouse pups were exposed to lead acetate via drinking water throughout gestation and until postnatal day 10, which is equivalent to the human gestation period for retinal neurogenesis. RT-qPCR, immunohistochemical analysis, and western blots of well-characterized, cell-specific genes and proteins were performed at embryonic and early postnatal ages to assess rod and cone photoreceptor differentiation, rod and BC differentiation and synaptic development, and Müller glial cell differentiation. Real-time quantitative PCR (RT-qPCR) with the rod-specific transcription factors Nrl , Nr2e3 , and Crx and the rod-specific functional gene Rho , along with central retinal confocal studies with anti-recoverin and anti-rhodopsin antibodies, revealed a two-day delay in the differentiation of rod photoreceptors in GLE retinas. Rhodopsin immunoblots supported this conclusion. No changes in glutamine synthetase gene

Response of Differentiated Human Airway Epithelia to Alcohol Exposure and Klebsiella pneumoniae Challenge

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Sammeta V. Raju

2013-07-01

Full Text Available Alcohol abuse has been associated with increased susceptibility to pulmonary infection. It is not fully defined how alcohol contributes to the host defense compromise. Here primary human airway epithelial cells were cultured at an air-liquid interface to form a differentiated and polarized epithelium. This unique culture model allowed us to closely mimic lung infection in the context of alcohol abuse by basolateral alcohol exposure and apical live bacterial challenge. Application of clinically relevant concentrations of alcohol for 24 h did not significantly alter epithelial integrity or barrier function. When apically challenged with viable Klebsiella pneumoniae, the cultured epithelia had an enhanced tightness which was unaffected by alcohol. Further, alcohol enhanced apical bacterial growth, but not bacterial binding to the cells. The cultured epithelium in the absence of any treatment or stimulation had a base-level IL-6 and IL-8 secretion. Apical bacterial challenge significantly elevated the basolateral secretion of inflammatory cytokines including IL-2, IL-4, IL-6, IL-8, IFN-γ, GM-CSF, and TNF-α. However, alcohol suppressed the observed cytokine burst in response to infection. Addition of adenosine receptor agonists negated the suppression of IL-6 and TNF-α. Thus, acute alcohol alters the epithelial cytokine response to infection, which can be partially mitigated by adenosine receptor agonists.

Increased expression of alpha- and beta-globin mRNAs at the pituitary following exposure to estrogen during the critical period of neonatal sex differentiation in the rat

DEFF Research Database (Denmark)

Leffers, H; Navarro, V M; Nielsen, John E

2006-01-01

Deterioration of reproductive health in human and wildlife species during the past decades has drawn considerable attention to the potential adverse effects of exposure to xenosteroids during sensitive periods of sex development. The hypothalamic-pituitary (HP) unit is a key element in the neuroe......Deterioration of reproductive health in human and wildlife species during the past decades has drawn considerable attention to the potential adverse effects of exposure to xenosteroids during sensitive periods of sex development. The hypothalamic-pituitary (HP) unit is a key element......, we screened for differentially expressed genes at the pituitary and hypothalamus of rats after neonatal exposure to estradiol benzoate. Our analyses identified persistent up-regulation of alpha- and beta-globin mRNAs at the pituitary following neonatal estrogenization. This finding was confirmed...... by combination of RT-PCR analyses and in situ hybridization. Induction of alpha- and beta-globin mRNA expression at the pituitary by neonatal exposure to estrogen was demonstrated as dose-dependent and it was persistently detected up to puberty. In contrast, durable up-regulation of alpha- and beta-globin genes...

Recent Understandings of Pet Allergies [version 1; referees: 2 approved

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Dennis Ownby

2016-01-01

Full Text Available Allergic reactions to pets have been recognized for at least a hundred years. Yet our understanding of the effects of all of the interactions between pet exposures and human immune responses continues to grow. Allergists, epidemiologists, and immunologists have spent years trying to better understand how exposures to pet allergens lead to allergic sensitization (the production of allergen-specific immunoglobulin class E [IgE] antibodies and subsequent allergic disease. A major new development in this understanding is the recognition that pet exposures consist of not only allergen exposures but also changes in microbial exposures. Exposures to certain pet-associated microbes, especially in the neonatal period, appear to be able to dramatically alter how a child’s immune system develops and this in turn reduces the risk of allergic sensitization and disease. An exciting challenge in the next few years will be to see whether these changes can be developed into a realistic preventative strategy with the expectation of significantly reducing allergic disease, especially asthma.

Assessment of Human Exposure to ENMs.

Science.gov (United States)

Jiménez, Araceli Sánchez; van Tongeren, Martie

2017-01-01

Human exposure assessment of engineered nanomaterials (ENMs) is hampered, among other factors, by the difficulty to differentiate ENM from other nanomaterials (incidental to processes or naturally occurring) and the lack of a single metric that can be used for health risk assessment. It is important that the exposure assessment is carried out throughout the entire life-cycle as releases can occur at the different stages of the product life-cycle, from the synthesis, manufacture of the nano-enable product (occupational exposure) to the professional and consumer use of nano-enabled product (consumer exposure) and at the end of life.Occupational exposure surveys should follow a tiered approach, increasing in complexity in terms of instruments used and sampling strategy applied with higher tiers in order tailor the exposure assessment to the specific materials used and workplace exposure scenarios and to reduce uncertainty in assessment of exposure. Assessment of consumer exposure and of releases from end-of-life processes currently relies on release testing of nano-enabled products in laboratory settings.

Perinatal exposure to diesel exhaust affects gene expression in mouse cerebrum

Energy Technology Data Exchange (ETDEWEB)

Tsukue, Naomi [Tokyo University of Science, Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Noda, Chiba (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kawaguchi, Saitama (Japan); Japan Automobile Research Institute, Health Effects Research Group, Energy and Environment Research Division, Tsukuba, Ibaraki (Japan); Watanabe, Manabu; Kumamoto, Takayuki; Takeda, Ken [Tokyo University of Science, Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Noda, Chiba (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kawaguchi, Saitama (Japan); Takano, Hirohisa [Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kawaguchi, Saitama (Japan); National Institute for Environmental Studies, Pathophysiology Research Team, Tsukuba, Ibaraki (Japan)

2009-11-15

Many environmental toxins alter reproductive function and affect the central nervous system (CNS). Gonadal steroid hormones cause differentiation of neurons and affect brain function and behavior during the perinatal period, and the CNS is thought to be particularly susceptible to toxic insult during this period. It was, therefore, hypothesized that inhalation of diesel exhaust (DE) during the fetal or suckling period would disrupt the sexual differentiation of brain function in mice, and the effects of exposure to DE during the perinatal period on sexual differentiation related gene expression of the brain were investigated. In the fetal period exposure group, pregnant ICR mice were exposed to DE from 1.5 days post-coitum (dpc) until 16 dpc. In the neonatal period exposure group, dams and their offspring were exposed to DE from the day of birth [postnatal day (PND)-0] until PND-16. Then, the cerebrums of males and females at PND-2, -5, and -16 from both groups were analyzed for expression level of mRNA encoding stress-related proteins [cytochrome P450 1A1 (CYP1A1), heme oxygenase-1 (HO-1)] and steroid hormone receptors [estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), androgen receptor (AR)]. Expression levels of ER alpha and ER beta mRNA were increased in the cerebrum of newborns in the DE exposure groups as well as mRNA for CYP1A1 and HO-1. Results indicate that perinatal exposure to DE during the critical period of sexual differentiation of the brain may affect endocrine function. (orig.)

Cadmium stimulates myofibroblast differentiation and mouse lung fibrosis

International Nuclear Information System (INIS)

Hu, Xin; Fernandes, Jolyn; Jones, Dean P.; Go, Young-Mi

2017-01-01

Highlights: • Low-dose Cd stimulates differentiation of human lung fibroblast to myofibroblast. • Cd-stimulated fibrosis signaling involves activation of SMAD transcription factor. • Low-dose Cd intake in mice activates myofibroblast differentiation. - Abstract: Increasing evidence suggests that Cd at levels found in the human diet can cause oxidative stress and activate redox-sensitive transcription factors in inflammatory signaling. Following inflammation, tissue repair often involves activation of redox-sensitive transcription factors in fibroblasts. In lungs, epithelial barrier remodeling is required to restore gas exchange and barrier function, and aberrant myofibroblast differentiation leads to pulmonary fibrosis. Contributions of exogenous exposures, such as dietary Cd, to pulmonary fibrosis remain inCompletely defined. In the current study, we tested whether Cd activates fibrotic signaling in human fetal lung fibroblasts (HFLF) at micromolar and submicromolar Cd concentrations that do not cause cell death. Exposure of HFLF to low-dose Cd (≤1.0 μM) caused an increase in stress fibers and increased protein levels of myofibroblast differentiation markers, including α-smooth muscle actin (α-SMA) and extra-domain-A-containing fibronectin (ED-A-FN). Assay of transcription factor (TF) activity using a 45-TF array showed that Cd increased activity of 12 TF, including SMAD2/3/4 (mothers against decapentaplegic homolog) signaling differentiation and fibrosis. Results were confirmed by real-time PCR and supported by increased expression of target genes of SMAD2/3/4. Immunocytochemistry of lungs of mice exposed to low-dose Cd (0.3 and 1.0 mg/L in drinking water) showed increased α-SMA protein level with lung Cd accumulation similar to lung Cd in non-smoking humans. Together, the results show that relatively low Cd exposures stimulate pulmonary fibrotic signaling and myofibroblast differentiation by activating SMAD2/3/4-dependent signaling. The results

Occupational exposure to electromagnetic fields and sex-differential risk of uveal melanoma

DEFF Research Database (Denmark)

Behrens, Thomas Flensted; Lynge, Elsebeth; Cree, Ian

2010-01-01

The association between occupational exposure to electromagnetic fields (EMF) and the risk of uveal melanoma was investigated in a case-control study in nine European countries.......The association between occupational exposure to electromagnetic fields (EMF) and the risk of uveal melanoma was investigated in a case-control study in nine European countries....

Understanding the occurrence of interracial marriage in the United States through differential assimilation.

Science.gov (United States)

Lewis, Richard; Ford-Robertson, Joanne

2010-01-01

American society is undergoing unprecedented cultural changes in the 21st century. This social transformation began with the civil rights movement in the 1960s. As the United States becomes more diverse, both racially and ethnically, equal access to a variety of social institutions and organizations becomes more challenging. With respect to marriage, popular media continually report the blurring of boundaries between racial and ethnic groups. As a result, there has been a tremendous increase in interracial dating and marriage over the past several decades. There are considerable differences between the occurrence of interracial dating and interracial marriage. Data suggest that there is a much higher level of interracial dating in comparison to interracial marriage. This research effort focuses on trends in interracial marriages in the United States between 1980 and 2006. Information from the U.S. Census Bureau was used to analyze changes in the number and frequency of interracial marriages in American society over a 22-year time frame. Differential assimilation is employed for understanding interracial marriage trends and distinguishing important statistical differences between marriages with a Black spouse and those interracial marriages not involving a Black spouse. This exploration provides important empirical findings for assessing the progress of assimilation in America.

Understanding workers' exposure: Systematic review and data-analysis of emission potential for NOAA

NARCIS (Netherlands)

Kuijpers, E.; Bekker, C.; Brouwer, D.; Feber, M. le; Fransman, W.

2017-01-01

Exposure assessment for nano-objects, and their aggregates and agglomerates (NOAA), has evolved from explorative research toward more comprehensive exposure assessment, providing data to further develop currently used conservative control banding (CB) tools for risk assessment. This study aims to

Epigenetics, obesity and early-life cadmium or lead exposure.

Science.gov (United States)

Park, Sarah S; Skaar, David A; Jirtle, Randy L; Hoyo, Cathrine

2017-01-01

Obesity is a complex and multifactorial disease, which likely comprises multiple subtypes. Emerging data have linked chemical exposures to obesity. As organismal response to environmental exposures includes altered gene expression, identifying the regulatory epigenetic changes involved would be key to understanding the path from exposure to phenotype and provide new tools for exposure detection and risk assessment. In this report, we summarize published data linking early-life exposure to the heavy metals, cadmium and lead, to obesity. We also discuss potential mechanisms, as well as the need for complete coverage in epigenetic screening to fully identify alterations. The keys to understanding how metal exposure contributes to obesity are improved assessment of exposure and comprehensive establishment of epigenetic profiles that may serve as markers for exposures.

Differential Top Cross-section Measurements

CERN Document Server

Fenton, Michael James; The ATLAS collaboration

2017-01-01

The top quark is the heaviest known fundamental particle. The measurement of the differential top-quark pair production cross-section provides a stringent test of advanced perturbative QCD calculations. The ATLAS collaboration has performed detailed measurements of those differential cross sections at a centre-of-mass energy of 13 TeV. This talk focuses on differential cross-section measurements in the lepton+jets final state, including using boosted top quarks to probe our understanding of top quark production in the TeV regime.

Wired on steroids: Sexual differentiation of the brain and its role in the expression of sexual partner preferences

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Brenda Mae Alexander

2011-10-01

Full Text Available The preference to seek out a sexual partner of the opposite sex is robust and ensures reproduction and survival of the species. Development of female-directed partner preference in the male is dependent on exposure of the developing brain to gonadal steroids synthesized during critical periods of sexual differentiation of the central nervous system. In the absence of androgen exposure, a male-directed partner preference develops. The development and expression of sexual partner preference has been extensively studied in rats, ferrets, and sheep model systems. From these models it is clear that gonadal testosterone, often through estrogenic metabolites, cause both masculinization and defeminization of behavior during critical periods of brain development. Changes in the steroid environment during these critical periods results in atypical sexual partner preference. In this manuscript, we review the major findings which support the hypothesis that the organizational actions of sex steroids are responsible for sexual differentiation of sexual partner preferences in select non-human species. We also explore how this information has helped to frame our understanding of the biological influences on human sexual orientation and gender identity.

Proteomic profiling of human keratinocytes undergoing UVB-induced alternative differentiation reveals TRIpartite Motif Protein 29 as a survival factor.

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Véronique Bertrand-Vallery

Full Text Available BACKGROUND: Repeated exposures to UVB of human keratinocytes lacking functional p16(INK-4a and able to differentiate induce an alternative state of differentiation rather than stress-induced premature senescence. METHODOLOGY/PRINCIPAL FINDINGS: A 2D-DIGE proteomic profiling of this alternative state of differentiation was performed herein at various times after the exposures to UVB. Sixty-nine differentially abundant protein species were identified by mass spectrometry, many of which are involved in keratinocyte differentiation and survival. Among these protein species was TRIpartite Motif Protein 29 (TRIM29. Increased abundance of TRIM29 following UVB exposures was validated by Western blot using specific antibody and was also further analysed by immunochemistry and by RT-PCR. TRIM29 was found very abundant in keratinocytes and reconstructed epidermis. Knocking down the expression of TRIM29 by short-hairpin RNA interference decreased the viability of keratinocytes after UVB exposure. The abundance of involucrin mRNA, a marker of late differentiation, increased concomitantly. In TRIM29-knocked down reconstructed epidermis, the presence of picnotic cells revealed cell injury. Increased abundance of TRIM29 was also observed upon exposure to DNA damaging agents and PKC activation. The UVB-induced increase of TRIM29 abundance was dependent on a PKC signaling pathway, likely PKCdelta. CONCLUSIONS/SIGNIFICANCE: These findings suggest that TRIM29 allows keratinocytes to enter a protective alternative differentiation process rather than die massively after stress.

Sex-based differences in gene expression in hippocampus following postnatal lead exposure

International Nuclear Information System (INIS)

Schneider, J.S.; Anderson, D.W.; Sonnenahalli, H.; Vadigepalli, R.

2011-01-01

The influence of sex as an effect modifier of childhood lead poisoning has received little systematic attention. Considering the paucity of information available concerning the interactive effects of lead and sex on the brain, the current study examined the interactive effects of lead and sex on gene expression patterns in the hippocampus, a structure involved in learning and memory. Male or female rats were fed either 1500 ppm lead-containing chow or control chow for 30 days beginning at weaning.Blood lead levels were 26.7 ± 2.1 μg/dl and 27.1 ± 1.7 μg/dl for females and males, respectively. The expression of 175 unique genes was differentially regulated between control male and female rats. A total of 167 unique genes were differentially expressed in response to lead in either males or females. Lead exposure had a significant effect without a significant difference between male and female responses in 77 of these genes. In another set of 71 genes, there were significant differences in male vs. female response. A third set of 30 genes was differentially expressed in opposite directions in males vs. females, with the majority of genes expressed at a lower level in females than in males. Highly differentially expressed genes in males and females following lead exposure were associated with diverse biological pathways and functions. These results show that a brief exposure to lead produced significant changes in expression of a variety of genes in the hippocampus and that the response of the brain to a given lead exposure may vary depending on sex. - Highlights: → Postnatal lead exposure has a significant effect on hippocampal gene expression patterns. → At least one set of genes was affected in opposite directions in males and females. → Differentially expressed genes were associated with diverse biological pathways.

Chondrogenic Differentiation of Mesenchymal Stem Cells: Challenges and Unfulfilled Expectations

Science.gov (United States)

Somoza, Rodrigo A.; Welter, Jean F.; Correa, Diego

2014-01-01

Articular cartilage repair and regeneration provides a substantial challenge in Regenerative Medicine because of the high degree of morphological and mechanical complexity intrinsic to hyaline cartilage due, in part, to its extracellular matrix. Cartilage remains one of the most difficult tissues to heal; even state-of-the-art regenerative medicine technology cannot yet provide authentic cartilage resurfacing. Mesenchymal stem cells (MSCs) were once believed to be the panacea for cartilage repair and regeneration, but despite years of research, they have not fulfilled these expectations. It has been observed that MSCs have an intrinsic differentiation program reminiscent of endochondral bone formation, which they follow after exposure to specific reagents as a part of current differentiation protocols. Efforts have been made to avoid the resulting hypertrophic fate of MSCs; however, so far, none of these has recreated a fully functional articular hyaline cartilage without chondrocytes exhibiting a hypertrophic phenotype. We reviewed the current literature in an attempt to understand why MSCs have failed to regenerate articular cartilage. The challenges that must be overcome before MSC-based tissue engineering can become a front-line technology for successful articular cartilage regeneration are highlighted. PMID:24749845

Solutions manual to accompany Ordinary differential equations

CERN Document Server

Greenberg, Michael D

2014-01-01

Features a balance between theory, proofs, and examples and provides applications across diverse fields of study Ordinary Differential Equations presents a thorough discussion of first-order differential equations and progresses to equations of higher order. The book transitions smoothly from first-order to higher-order equations, allowing readers to develop a complete understanding of the related theory. Featuring diverse and interesting applications from engineering, bioengineering, ecology, and biology, the book anticipates potential difficulties in understanding the various solution steps

Cathepsin S Is Involved in Th17 Differentiation Through the Upregulation of IL-6 by Activating PAR-2 after Systemic Exposure to Lipopolysaccharide from Porphyromonas gingivalis

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Masato Dekita

2017-07-01

Full Text Available Positive links have been found between periodontitis and numerous diseases in humans via persistent inflammation throughout the body. However, the main factors responsible for maintaining this pro-inflammatory condition are poorly understood. The spleen, the largest secondary immune organ, is a central hub regulating the immune response/inflammation due to the dendritic cell (DC response to CD4+ T cell subtype differentiation, and lysosomal proteinase cathepsin S (CatS is known to be involved in DC functions. In the present study, we found that CatS-induced IL-6 production by splenic DCs subsequently promotes Th17 differentiation, in response to systemic exposure to lipopolysaccharide derived from Porphyromonas gingivalis (PgLPS. The population of CD11c+ DCs was significantly increased in the splenic marginal zone (MZ locally of wild-type (DBA/2 mice with splenomegaly but not in that of CatS deficient (CatS-/- mice after systemic exposure to PgLPS for 7 consecutive days (5 mg/kg/day, intraperitoneal. Similarly, the population of Th17+CD4+ T cells was also significantly increased in the splenic MZ of wild-type mice but not in that of CatS-/- mice after PgLPS exposure. Furthermore, the increase in the Th17+ CD4+ T cell population paralleled increases in the levels of CatS and IL-6 in CD11c+ cells in the splenic MZ. In isolated primary splenic CD11c+ cells, the mRNA expression and the production of IL-6 was dramatically increased in wild-type mice but not in CatS-/- mice after direct stimulation with PgLPS (1 μg/ml, and this PgLPS-induced increase in the IL-6 expression was completely abolished by pre-treatment with Z-Phe-Leu-COCHO (Z-FL, the specific inhibitor of CatS. The PgLPS activated protease-activated receptor (PAR 2 in the isolated splenic CD11c+ cells was also significantly inhibited by CatS deficiently. In addition, the PgLPS-induced increase in the IL-6 production by splenic CD11c+ cells was completely abolished by pre-treatment with

An in vivo model fish system to test chemical effects on sexual differentiation and development: exposure to ethinyl estradiol

Science.gov (United States)

Papoulias, Diana M.; Noltie, Douglas B.; Tillitt, Donald E.

2000-01-01

A model system was characterized which may be used as an in vivo screen for effects of chemicals or environmental mixtures on sexual differentiation and development of reproductive organs and gametes. We evaluated the effects of a model environmental estrogen, ethinyl estradiol (EE2), on the d-rR strain of medaka, Oryzias latipes, using a nano-injection exposure. Gonad histopathology indicated that a single injection of 0.5–2.5 ng EE2/egg can cause phenotypic sex-reversal of genetic males to females. Sex-reversals could be detected as early as 7 days post-hatch. Sex-reversed males had female-typical duct development and the secondary sex characteristics we measured were generally consistent with phenotype, with the exception of a few EE2-exposed XX and XY females which possessed ambiguous anal fins. Using discriminant analysis, we determined that the presence or absence of the secondary sex characteristic, a dorsal fin notch, was a very reliable indicator of gonadal sex. No instances of gonadal intersexes were observed. Ethinyl estradiol also appeared to reduce growth but not condition (weight-at-length) and exposed XX females appeared to have a higher incidence of atretic follicles relative to controls. Our results suggest that estrogenic chemicals may influence sexual differentiation and development and that the medaka model is well suited to assessing these effects.

Impulsive Choice, Alcohol Consumption, and Pre-Exposure to Delayed Rewards: II. Potential Mechanisms

Science.gov (United States)

Stein, Jeffrey S.; Renda, C. Renee; Hinnenkamp, Jay E.; Madden, Gregory J.

2014-01-01

In a prior study (Stein et al., 2013), we reported that rats pre-exposed to delayed rewards made fewer impulsive choices, but consumed more alcohol (12% wt/vol), than rats pre-exposed to immediate rewards. To understand the mechanisms that produced these findings, we again pre-exposed rats to either delayed (17.5 s; n = 32) or immediate (n = 30) rewards. In post-tests, delay-exposed rats made significantly fewer impulsive choices at both 15- and 30-s delays to a larger, later food reward than the immediacy-exposed comparison group. Behavior in an open-field test provided little evidence of differential stress exposure between groups. Further, consumption of either 12% alcohol or isocaloric sucrose in subsequent tests did not differ between groups. Because Stein et al. introduced alcohol concentration gradually (3–12%), we speculate that their group differences in 12% alcohol consumption were not determined by alcohol’s pharmacological effects, but by another variable (e.g., taste) that was preserved as an artifact from lower concentrations. We conclude that pre-exposure to delayed rewards generalizes beyond the pre-exposure delay; however, this same experimental variable does not robustly influence alcohol consumption. PMID:25418607

Exposure to an organophosphate pesticide, individually or in combination with other Gulf War agents, impairs synaptic integrity and neuronal differentiation, and is accompanied by subtle microvascular injury in a mouse model of Gulf War agent exposure.

Science.gov (United States)

Ojo, Joseph O; Abdullah, Laila; Evans, James; Reed, Jon Mike; Montague, Hannah; Mullan, Michael J; Crawford, Fiona C

2014-04-01

Gulf War illness (GWI) is a currently untreatable multi-symptom disorder experienced by 1990-1991 Persian Gulf War (GW) veterans. The characteristic hallmarks of GWI include cognitive dysfunction, tremors, migraine, and psychological disturbances such as depression and anxiety. Meta-analyses of epidemiological studies have consistently linked these symptomatic profiles to the combined exposure of GW agents such as organophosphate-based and pyrethroid-based pesticides (e.g. chlorpyrifos (CPF) and permethrin (PER) respectively) and the prophylactic use of pyridostigmine bromide (PB) as a treatment against neurotoxins. Due to the multi-symptomatic presentation of this illness and the lack of available autopsy tissue from GWI patients, very little is currently known about the distinct early pathological profile implicated in GWI (including its influence on synaptic function and aspects of neurogenesis). In this study, we used preclinical models of GW agent exposure to investigate whether 6-month-old mice exposed to CPF alone, or a combined dose of CPF, PB and PER daily for 10 days, demonstrate any notable pathological changes in hippocampal, cortical (motor, piriform) or amygdalar morphometry. We report that at an acute post-exposure time point (after 3 days), both exposures resulted in the impairment of synaptic integrity (reducing synaptophysin levels) in the CA3 hippocampal region and altered neuronal differentiation in the dentate gyrus (DG), demonstrated by a significant reduction in doublecortin positive cells. Both exposures also significantly increased astrocytic GFAP immunoreactivity in the piriform cortex, motor cortex and the basolateral amygdala and this was accompanied by an increase in (basal) brain acetylcholine (ACh) levels. There was no evidence of microglial activation or structural deterioration of principal neurons in these regions following exposure to CPF alone or in combination with PB and PER. Evidence of subtle microvascular injury was

Understanding of radiation protection in medicine. Pt. 2. Occupational exposure and system of radiation protection

International Nuclear Information System (INIS)

Iida, Hiroji; Yamamoto, Tomoyuki; Shimada, Yasuhiro

1997-01-01

Using a questionnaire we investigated whether radiation protection is correctly understood by medical doctors (n=140) and nurses (n=496). Although medical exposure is usually understood by medical doctors and dentists, their knowledge was found to be insufficient. Sixty-eight percent of medical doctors and 50% of dentists did not know about the system of radiation protection. Dose monitoring was not correctly carried out by approximately 20% of medical staff members, and medical personnel generally complained of anxiety about occupational exposure rather than medical exposure. They did not receive sufficient education on radiation exposure and protection in school. In conclusion, the results of this questionnaire suggested that they do not have adequate knowledge about radiation exposure and protection. The lack of knowledge about protection results in anxiety about exposure. To protect oneself from occupational exposure, individual radiation doses must be monitored, and medical practice should be reconsidered based on the results of monitoring. To eliminate unnecessary medical and occupational exposure and to justify practices such as radiological examinations, radiation protection should be well understood and appropriately carried out by medical doctors and dentists. Therefore, the education of medical students on the subject of radiation protection is required as is postgraduate education for medical doctors, dentists and nurses. (author)

Global gene expression in larval zebrafish (Danio rerio) exposed to selective serotonin reuptake inhibitors (fluoxetine and sertraline) reveals unique expression profiles and potential biomarkers of exposure

International Nuclear Information System (INIS)

Park, June-Woo; Heah, Tze Ping; Gouffon, Julia S.; Henry, Theodore B.; Sayler, Gary S.

2012-01-01

Larval zebrafish (Danio rerio) were exposed (96 h) to selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and changes in transcriptomes analyzed by Affymetrix GeneChip ® Zebrafish Array were evaluated to enhance understanding of biochemical pathways and differences between these SSRIs. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 μg/L and 131 at 250 μg/L; and after sertraline exposure was 33 at 25 μg/L and 52 at 250 μg/L. Same five genes were differentially regulated in both SSRIs indicating shared molecular pathways. Among these, the gene coding for FK506 binding protein 5, annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated at the gene expression level that regulation of stress response and cholinesterase activities were influenced by these SSRIs, and suggested that changes in transcription of these genes could be used as biomarkers of SSRI exposure. - Highlights: ► Exposure of zebrafish to selective serotonin reuptake inhibitors (SSRIs). ► Fluoxetine and sertraline generate different global gene expression profiles. ► Genes linked to stress response and acetylcholine esterase affected by both SSRIs. - Global gene expression profiles in zebrafish exposed to selective serotonin reuptake inhibitors.

Analysis of Dextromethorphan and Dextrorphan in Skeletal Remains Following Differential Microclimate Exposure: Comparison of Acute vs. Repeated Drug Exposure.

Science.gov (United States)

Morrison, Lucas M; Unger, Kirk A; Watterson, James H

2017-07-01

Analysis of dextromethorphan (DXM) and its metabolite dextrorphan (DXT) in skeletal remains of rats following acute (ACU, 75 mg/kg, IP, n = 10) or three repeated (REP, 25 mg/kg, IP, n = 10, 40-min interval) doses of DXM is described. Following dosing and euthanasia, rats decomposed outdoors to skeleton in two different microclimate environments (n = 5 ACU and n = 5 REP at each site): Site A (shaded forest microenvironment) and Site B (rocky substrate exposed to direct sunlight, 600 m from Site A). Two drug-free rats at each site served as negative controls. Skeletal elements (vertebrae, ribs, pelvic girdles, femora, tibiae, skulls and scapulae) were recovered, pulverized and underwent methanolic microwave assisted extraction (MAE). Extracts were analyzed by GC-MS following clean-up by solid-phase extraction (SPE). Drug levels, expressed as mass-normalized response ratios and the ratios of DXT and DXM levels (RRDXT/RRDXM) were compared between drug exposures, microclimate sites, and across skeletal elements. DXM levels differed significantly (P < 0.05) between corresponding bone elements across exposure groups (5/7-site A; 4/7-site B), but no significant differences in DXT levels were observed between corresponding elements. RRDXT/RRDXM differed significantly (P < 0.05) between corresponding bone elements across exposure groups (6/7-site A; 5/7-site B). No significant differences were observed in levels of DXM, DXT or RRDXT/RRDXM between corresponding elements from either group between sites. When data from all bone elements was pooled, levels of DXM and RRDXT/RRDXM differed significantly between exposure groups at each site, while those of DXT did not. For both exposure groups, comparison of pooled data between sites showed no significant differences in levels of DXM, DXT or RRDXT/RRDXM. Different decomposition microclimates did not impede the discrimination of DXM exposure patterns from the analyses of DXM, DXT and RRDXT/RRDXM in bone samples. © The Author 2017

Lessons learned from perinatal exposure to diethylstilbestrol

Energy Technology Data Exchange (ETDEWEB)

Newbold, Retha R

2004-09-01

The synthetic estrogen diethylstilbestrol (DES) is well documented to be a perinatal carcinogen in both humans and experimental animals. Exposure to DES during critical periods of differentiation permanently alters the programming of estrogen target tissues resulting in benign and malignant abnormalities in the reproductive tract later in life. Using the perinatal DES-exposed rodent model, cellular and molecular mechanisms have been identified that play a role in these carcinogenic effects. Although DES is a potent estrogenic chemical, effects of low doses of the compound are being used to predict health risks of weaker environmental estrogens. Therefore, it is of particular interest that developmental exposure to very low doses of DES has been found to adversely affect fertility and to increase tumor incidence in murine reproductive tract tissues. These adverse effects are seen at environmentally relevant estrogen dose levels. New studies from our lab verify that DES effects are not unique; when numerous environmental chemicals with weak estrogenic activity are tested in the experimental neonatal mouse model, developmental exposure results in an increased incidence of benign and malignant tumors including uterine leiomyomas and adenocarcinomas that are similar to those shown following DES exposure. Finally, growing evidence in experimental animals suggests that some adverse effects can be passed on to subsequent generations, although the mechanisms involved in these trans-generational events remain unknown. Although the complete spectrum of risks to DES-exposed humans are uncertain at this time, the scientific community continues to learn more about cellular and molecular mechanisms by which perinatal carcinogenesis occurs. These advances in knowledge of both genetic and epigenetic mechanisms will be significant in ultimately predicting risks to other environmental estrogens and understanding more about the role of estrogens in normal and abnormal development.

Lessons learned from perinatal exposure to diethylstilbestrol

International Nuclear Information System (INIS)

Newbold, Retha R.

2004-01-01

The synthetic estrogen diethylstilbestrol (DES) is well documented to be a perinatal carcinogen in both humans and experimental animals. Exposure to DES during critical periods of differentiation permanently alters the programming of estrogen target tissues resulting in benign and malignant abnormalities in the reproductive tract later in life. Using the perinatal DES-exposed rodent model, cellular and molecular mechanisms have been identified that play a role in these carcinogenic effects. Although DES is a potent estrogenic chemical, effects of low doses of the compound are being used to predict health risks of weaker environmental estrogens. Therefore, it is of particular interest that developmental exposure to very low doses of DES has been found to adversely affect fertility and to increase tumor incidence in murine reproductive tract tissues. These adverse effects are seen at environmentally relevant estrogen dose levels. New studies from our lab verify that DES effects are not unique; when numerous environmental chemicals with weak estrogenic activity are tested in the experimental neonatal mouse model, developmental exposure results in an increased incidence of benign and malignant tumors including uterine leiomyomas and adenocarcinomas that are similar to those shown following DES exposure. Finally, growing evidence in experimental animals suggests that some adverse effects can be passed on to subsequent generations, although the mechanisms involved in these trans-generational events remain unknown. Although the complete spectrum of risks to DES-exposed humans are uncertain at this time, the scientific community continues to learn more about cellular and molecular mechanisms by which perinatal carcinogenesis occurs. These advances in knowledge of both genetic and epigenetic mechanisms will be significant in ultimately predicting risks to other environmental estrogens and understanding more about the role of estrogens in normal and abnormal development

Income Inequality and US Children's Secondhand Smoke Exposure: Distinct Associations by Race-Ethnicity.

Science.gov (United States)

Shenassa, Edmond D; Rossen, Lauren M; Cohen, Jonathan; Morello-Frosch, Rachel; Payne-Sturges, Devon C

2017-11-01

Prior studies have found considerable racial and ethnic disparities in secondhand smoke (SHS) exposure. Although a number of individual-level determinants of this disparity have been identified, contextual determinants of racial and ethnic disparities in SHS exposure remain unexamined. The objective of this study was to examine disparities in serum cotinine in relation to area-level income inequality among 14 649 children from the National Health and Nutrition Examination Survey. We fit log-normal regression models to examine disparities in serum cotinine in relation to Metropolitan Statistical Areas level income inequality among 14 649 nonsmoking children aged 3-15 from the National Health and Nutrition Examination Survey (1999-2012). Non-Hispanic black children had significantly lower serum cotinine than non-Hispanic white children (-0.26; 95% CI: -0.38, -0.15) in low income inequality areas, but this difference was attenuated in areas with high income inequality (0.01; 95% CI: -0.16, 0.18). Serum cotinine declined for non-Hispanic white and Mexican American children with increasing income inequality. Serum cotinine did not change as a function of the level of income inequality among non-Hispanic black children. We have found evidence of differential associations between SHS exposure and income inequality by race and ethnicity. Further examination of environments which engender SHS exposure among children across various racial/ethnic subgroups can foster a better understanding of how area-level income inequality relates to health outcomes such as levels of SHS exposure and how those associations differ by race/ethnicity. In the United States, the association between children's risk of SHS exposure and income inequality is modified by race/ethnicity in a manner that is inconsistent with theories of income inequality. In overall analysis this association appears to be as predicted by theory. However, race-specific analyses reveal that higher levels of income

Understanding MIH: definition, epidemiology, differential diagnosis and new treatment guidelines.

Science.gov (United States)

Mast, P; Rodrigueztapia, M T; Daeniker, L; Krejci, I

2013-09-01

Molar-Incisor Hypomineralisation (MIH) is a congenital disease which increases in prevalence. It affects permanent first molars and, often to a lesser degree, permanent incisors with variable severity. The aetiology is unknown, but different hypotheses have been advanced. Differential diagnosis is mandatory not to confound MIH with other diseases. Treatment consists in a minimally invasive approach by reinforcing and protecting the existing dental structure. In more severe cases, restorative treatment may be indicated.

Mitochondrial biogenesis and energy production in differentiating murine stem cells: a functional metabolic study.

Science.gov (United States)

Han, Sungwon; Auger, Christopher; Thomas, Sean C; Beites, Crestina L; Appanna, Vasu D

2014-02-01

The significance of metabolic networks in guiding the fate of the stem cell differentiation is only beginning to emerge. Oxidative metabolism has been suggested to play a major role during this process. Therefore, it is critical to understand the underlying mechanisms of metabolic alterations occurring in stem cells to manipulate the ultimate outcome of these pluripotent cells. Here, using P19 murine embryonal carcinoma cells as a model system, the role of mitochondrial biogenesis and the modulation of metabolic networks during dimethyl sulfoxide (DMSO)-induced differentiation are revealed. Blue native polyacrylamide gel electrophoresis (BN-PAGE) technology aided in profiling key enzymes, such as hexokinase (HK) [EC 2.7.1.1], glucose-6-phosphate isomerase (GPI) [EC 5.3.1.9], pyruvate kinase (PK) [EC 2.7.1.40], Complex I [EC 1.6.5.3], and Complex IV [EC 1.9.3.1], that are involved in the energy budget of the differentiated cells. Mitochondrial adenosine triphosphate (ATP) production was shown to be increased in DMSO-treated cells upon exposure to the tricarboxylic acid (TCA) cycle substrates, such as succinate and malate. The increased mitochondrial activity and biogenesis were further confirmed by immunofluorescence microscopy. Collectively, the results indicate that oxidative energy metabolism and mitochondrial biogenesis were sharply upregulated in DMSO-differentiated P19 cells. This functional metabolic and proteomic study provides further evidence that modulation of mitochondrial energy metabolism is a pivotal component of the cellular differentiation process and may dictate the final destiny of stem cells.

Prenatal exposure to dietary fat induces changes in the transcriptional factors, TEF and YAP, which may stimulate differentiation of peptide neurons in rat hypothalamus.

Directory of Open Access Journals (Sweden)

Kinning Poon

Full Text Available Gestational exposure to a high-fat diet (HFD stimulates the differentiation of orexigenic peptide-expressing neurons in the hypothalamus of offspring. To examine possible mechanisms that mediate this phenomenon, this study investigated the transcriptional factor, transcription enhancer factor-1 (TEF, and co-activator, Yes-associated protein (YAP, which when inactivated stimulate neuronal differentiation. In rat embryos and postnatal offspring prenatally exposed to a HFD compared to chow, changes in hypothalamic TEF and YAP and their relationship to the orexigenic peptide, enkephalin (ENK, were measured. The HFD offspring at postnatal day 15 (P15 exhibited in the hypothalamic paraventricular nucleus a significant reduction in YAP mRNA and protein, and increased levels of inactive and total TEF protein, with no change in mRNA. Similarly, HFD-exposed embryos at embryonic day 19 (E19 showed in whole hypothalamus significantly decreased levels of YAP mRNA and protein and TEF mRNA, and increased levels of inactive TEF protein, suggesting that HFD inactivates TEF and YAP. This was accompanied by increased density and fluorescence intensity of ENK neurons. A close relationship between TEF and ENK was suggested by the finding that TEF co-localizes with this peptide in hypothalamic neurons and HFD reduced the density of TEF/ENK co-labeled neurons, even while the number and fluorescence intensity of single-labeled TEF neurons were increased. Increased YAP inactivity by HFD was further evidenced by a decrease in number and fluorescence intensity of YAP-containing neurons, although the density of YAP/ENK co-labeled neurons was unaltered. Genetic knockdown of TEF or YAP stimulated ENK expression in hypothalamic neurons, supporting a close relationship between these transcription factors and neuropeptide. These findings suggest that prenatal HFD exposure inactivates both hypothalamic TEF and YAP, by either decreasing their levels or increasing their inactive

Comparing exposure zones by different exposure metrics using statistical parameters: contrast and precision.

Science.gov (United States)

Park, Ji Young; Ramachandran, Gurumurthy; Raynor, Peter C; Eberly, Lynn E; Olson, Greg

2010-10-01

Recently, the appropriateness of using the 'mass concentration' metric for ultrafine particles has been questioned and surface area (SA) or number concentration metrics has been proposed as alternatives. To assess the abilities of various exposure metrics to distinguish between different exposure zones in workplaces with nanoparticle aerosols, exposure concentrations were measured in preassigned 'high-' and 'low-'exposure zones in a restaurant, an aluminum die-casting factory, and a diesel engine laboratory using SA, number, and mass concentration metrics. Predetermined exposure classifications were compared by each metric using statistical parameters and concentration ratios that were calculated from the different exposure concentrations. In the restaurant, SA and fine particle number concentrations showed significant differences between the high- and low-exposure zones and they had higher contrast (the ratio of between-zone variance to the sum of the between-zone and within-zone variances) than mass concentrations. Mass concentrations did not show significant differences. In the die cast facility, concentrations of all metrics were significantly greater in the high zone than in the low zone. SA and fine particle number concentrations showed larger concentration ratios between the high and low zones and higher contrast than mass concentrations. None of the metrics were significantly different between the high- and low-exposure zones in the diesel engine laboratory. The SA and fine particle number concentrations appeared to be better at differentiating exposure zones and finding the particle generation sources in workplaces generating nanoparticles. Because the choice of an exposure metric has significant implications for epidemiologic studies and industrial hygiene practice, a multimetric sampling approach is recommended for nanoparticle exposure assessment.

Epistaxis management: current understanding amongst junior doctors.

Science.gov (United States)

Fox, R; Nash, R; Liu, Z-W; Singh, A

2016-03-01

Epistaxis is a common and potentially life-threatening emergency. This survey assesses understanding and confidence in epistaxis management amongst current junior doctors. A cross-sectional study was conducted of foundation year one and two doctors based at three National Health Service trusts within a single region of the UK, assessing basic understanding and procedural confidence. A total of 111 foundation doctors completed this survey. The average duration of undergraduate exposure to otolaryngology was 8.1 days. Forty-one per cent of respondents stated that they would apply pressure to the nasal bones to control epistaxis. Seventy-five per cent lacked confidence in their ability to manage epistaxis. Those with two weeks or more of undergraduate exposure to otolaryngology were more confident than those with one week or less of exposure (p epistaxis management, with patient safety implications. Confidence is associated with the duration of undergraduate exposure to otolaryngology. A minimum emergency safe competency should be a priority during foundation training if not achieved in UK medical schools.

Cell death following thermal neutron exposure

Energy Technology Data Exchange (ETDEWEB)

Paterson, L.C. [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada); Atanackovic, J. [Ontario Power Generation, Toronto, Ontario (Canada); Boyer, C. [Canadian Neutron Beam Centre, Chalk River, Ontario (Canada); El-Jaby, S.; Priest, N.D. [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada); Seymour, C.B.; Boreham, D.R. [McMaster Univ., Hamilton, Ontario (Canada); Richardson, R.B. [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada)

2014-07-01

When individuals are exposed to unknown external ionizing radiation, it is desirable to have the means to assess both the absorbed dose received (Gy) and the radiation quality. Yet, conventional biodosimetry techniques, specifically the dicentric chromosome assay, cannot differentiate between the damage caused by high- and low-linear energy transfer (LET) exposures. Frequencies of apoptosis and necrosis, may provide an alternative method that assesses both the absorbed dose and radiation quality after unknown exposures. For this preliminary study, human lymphocytes were irradiated with {sup 60}Co gamma rays and thermal neutrons. Both apoptosis and necrosis increased with increasing gamma dose. In contrast, no dose-response was observed following thermal neutron exposure at doses up to 2.61 Gy. (author)

Self-reported acute health symptoms and exposure to companion animals

Science.gov (United States)

Background: In order to understand the etiological burden of disease associated with acute health symptoms (e.g. gastrointestinal [GI], respiratory, dermatological), it is important to understand how common exposures influence these symptoms. Exposures to familiar and unfamiliar ...

ENVIRONMENTAL ANTIANDROGENS: LOW DOSES OF VINCLOZOLIN ALTER SEXUAL DIFFERENTIATION OF THE MALE RAT

Science.gov (United States)

In humans and rodents, exposure to antiandrogenic chemicals during sexual differentiation can produce malformations of the reproductive tract. Perinatal administration of 100 or 200 mg vinclozolin (V) kg-1 day-1 during sexual differentiation in rats induces female-like anogenital...

Partial differential equations

CERN Document Server

Evans, Lawrence C

2010-01-01

This text gives a comprehensive survey of modern techniques in the theoretical study of partial differential equations (PDEs) with particular emphasis on nonlinear equations. The exposition is divided into three parts: representation formulas for solutions; theory for linear partial differential equations; and theory for nonlinear partial differential equations. Included are complete treatments of the method of characteristics; energy methods within Sobolev spaces; regularity for second-order elliptic, parabolic, and hyperbolic equations; maximum principles; the multidimensional calculus of variations; viscosity solutions of Hamilton-Jacobi equations; shock waves and entropy criteria for conservation laws; and, much more.The author summarizes the relevant mathematics required to understand current research in PDEs, especially nonlinear PDEs. While he has reworked and simplified much of the classical theory (particularly the method of characteristics), he primarily emphasizes the modern interplay between funct...

An introduction to neural network methods for differential equations

CERN Document Server

Yadav, Neha; Kumar, Manoj

2015-01-01

This book introduces a variety of neural network methods for solving differential equations arising in science and engineering. The emphasis is placed on a deep understanding of the neural network techniques, which has been presented in a mostly heuristic and intuitive manner. This approach will enable the reader to understand the working, efficiency and shortcomings of each neural network technique for solving differential equations. The objective of this book is to provide the reader with a sound understanding of the foundations of neural networks, and a comprehensive introduction to neural network methods for solving differential equations together with recent developments in the techniques and their applications. The book comprises four major sections. Section I consists of a brief overview of differential equations and the relevant physical problems arising in science and engineering. Section II illustrates the history of neural networks starting from their beginnings in the 1940s through to the renewed...

Identification of Differential Gene Expression Patterns after Acute Exposure to High and Low Doses of Low-LET Ionizing Radiation in a Reconstituted Human Skin Tissue

Energy Technology Data Exchange (ETDEWEB)

Tilton, Susan C.; Markillie, Lye Meng; Hays, Spencer; Taylor, Ronald C.; Stenoien, David L.

2016-11-01

Our goal here was to identify dose and temporal dependent radiation responses in a complex tissue, reconstituted human skin. Direct sequencing of RNA (RNA-seq) was used to quantify altered transcripts following exposure to 0.1, 2 and 10 Gy of ionizing radiation at 3 and 8 hours. These doses include a low dose in the range of some medical diagnostic procedures (0.1 Gy), a dose typically received during radiotherapy (2.0 Gy) and a lethal dose (10 Gy). These doses could be received after an intentional or accidental radiation exposure and biomarkers are needed to rapidly and accurately triage exposed individuals. A total of 1701 genes were deemed to be significantly affected by high dose radiation exposure with the majority of genes affected at 10 Gy. A group of 29 genes including GDF15, BBC3, PPM1D, FDXR, GADD45A, MDM2, CDKN1A, TP53INP1, CYCSP27, SESN1, SESN2, PCNA, and AEN were similarly altered at both 2 and 10 Gy, but not 0.1 Gy, at multiple time points. A much larger group of up regulated genes, including those involved in inflammatory responses, was significantly altered only after a 10 Gy exposure. At high doses, down regulated genes were associated with cell cycle regulation and exhibited an apparent linear response between 2 and 10 Gy. While only a handful of genes were significantly affected by 0.1 Gy exposure using stringent statistical filters, groups of related genes regulating cell cycle progression and inflammatory responses consistently exhibited opposite trends in their regulation compared to the high dose exposures. Differential regulation of PLK1 signaling at low and high doses was confirmed using qRT-PCR. These results indicate that some alterations in gene expression are qualitatively different at low and high doses of radiation in this model system.

Atmospheric Ionizing Radiation and Human Exposure

Science.gov (United States)

Wilson, John W.; Mertens, Christopher J.; Goldhagen, Paul; Friedberg, W.; DeAngelis, G.; Clem, J. M.; Copeland, K.; Bidasaria, H. B.

2005-01-01

Atmospheric ionizing radiation is of interest, apart from its main concern of aircraft exposures, because it is a principal source of human exposure to radiations with high linear energy transfer (LET). The ionizing radiations of the lower atmosphere near the Earth s surface tend to be dominated by the terrestrial radioisotopes. especially along the coastal plain and interior low lands, and have only minor contributions from neutrons (11 percent). The world average is substantially larger but the high altitude cities especially have substantial contributions from neutrons (25 to 45 percent). Understanding the world distribution of neutron exposures requires an improved understanding of the latitudinal, longitudinal, altitude and spectral distribution that depends on local terrain and time. These issues are being investigated in a combined experimental and theoretical program. This paper will give an overview of human exposures and describe the development of improved environmental models.

Atmospheric Ionizing Radiation and Human Exposure

Science.gov (United States)

Wilson, J. W.; Goldhagen, P.; Friedberg, W.; DeAngelis, G.; Clem, J. M.; Copeland, K.; Bidasaria, H. B.

2004-01-01

Atmospheric ionizing radiation is of interest, apart from its main concern of aircraft exposures, because it is a principal source of human exposure to radiations with high linear energy transfer (LET). The ionizing radiations of the lower atmosphere near the Earth s surface tend to be dominated by the terrestrial radioisotopes especially along the coastal plain and interior low lands and have only minor contributions from neutrons (11 percent). The world average is substantially larger but the high altitude cities especially have substantial contributions from neutrons (25 to 45 percent). Understanding the world distribution of neutron exposures requires an improved understanding of the latitudinal, longitudinal, altitude and spectral distribution that depends on local terrain and time. These issues are being investigated in a combined experimental and theoretical program. This paper will give an overview of human exposures and describe the development of improved environmental models.

Effects of Pulsed Electromagnetic Field on Differentiation of HUES-17 Human Embryonic Stem Cell Line

Directory of Open Access Journals (Sweden)

Yi-Lin Wu

2014-08-01

Full Text Available Electromagnetic fields are considered to potentially affect embryonic development, but the mechanism is still unknown. In this study, human embryonic stem cell (hESC line HUES-17 was applied to explore the mechanism of exposure on embryonic development to pulsed electromagnetic field (PEMF for 400 pulses at different electric field intensities and the differentiation of HUES-17 cells was observed after PEMF exposure. The expression of alkaline phosphatase (AP, stage-specific embryonic antigen-3 (SSEA-3, SSEA-4 and the mRNA level and protein level of Oct4, Sox2 and Nanog in HUES-17 cells remained unchanged after PEMF exposure at the electric field intensities of 50, 100, 200 or 400 kV/m. Four hundred pulses PEMF exposure at the electric field intensities of 50, 100, 200 or 400 kV/m did not affect the differentiation of HUES-17 cells. The reason why electromagnetic fields affect embryonic development may be due to other mechanisms rather than affecting the differentiation of embryonic stem cells.

Differential tolerance to cyanobacterial exposure between geographically distinct populations of Perca fluviatilis.

Science.gov (United States)

Persson, Karl-Johan; Bergström, Kristofer; Mazur-Marzec, Hannah; Legrand, Catherine

2013-12-15

Toxic cyanobacterial blooms are an important problem worldwide. Cyanobacteria may negatively impact young-of-the-year (YOY) fish directly (toxin production, turbidity, decrease in water quality) or indirectly (trophic toxin transfer, changes in prey species composition). Here we test whether there are any differences in cyanobacterial tolerance between four geographically distinct populations of European perch (Perca fluviatilis). We show that P. fluviatilis may develop tolerance against cyanobacteria demonstrated by the ability of individuals from a marine site (exposed to annual cyanobacterial blooms) to increase their detoxification more than individuals from an oligotrophic site (rarely exposed to cyanobacteria). Our results also revealed significant interaction effects between genotypes within a population and response to cyanobacterial exposure in terms of absolute growth and detoxification activity. This genotype by treatment interaction may result in local adaptations to cyanobacterial exposure in P. fluviatilis. Hence, the sensitivity against cyanobacterial exposure may differ between within species populations increasing the importance of local management of fish populations. Copyright © 2013 Elsevier Ltd. All rights reserved.

Exposure is not enough: suppressing stimuli from awareness can abolish the mere exposure effect.

Directory of Open Access Journals (Sweden)

Daniel de Zilva

Full Text Available Passive exposure to neutral stimuli increases subsequent liking of those stimuli--the mere exposure effect. Because of the broad implications for understanding and controlling human preferences, the role of conscious awareness in mere exposure has received much attention. Previous studies have claimed that the mere exposure effect can occur without conscious awareness of the stimuli. In two experiments, we applied a technique new to the mere exposure literature, called continuous flash suppression, to expose stimuli for a controlled duration with and without awareness. To ensure the reliability of the awareness manipulation, awareness was monitored on a trial-by-trial basis. Our results show that under these conditions the mere exposure effect does not occur without conscious awareness. In contrast, only when participants were aware of the stimuli did exposure increase liking and recognition. Together these data are consistent with the idea that the mere exposure effect requires conscious awareness and has important implications for theories of memory and affect.

Exposure is not enough: suppressing stimuli from awareness can abolish the mere exposure effect.

Science.gov (United States)

de Zilva, Daniel; Vu, Luke; Newell, Ben R; Pearson, Joel

2013-01-01

Passive exposure to neutral stimuli increases subsequent liking of those stimuli--the mere exposure effect. Because of the broad implications for understanding and controlling human preferences, the role of conscious awareness in mere exposure has received much attention. Previous studies have claimed that the mere exposure effect can occur without conscious awareness of the stimuli. In two experiments, we applied a technique new to the mere exposure literature, called continuous flash suppression, to expose stimuli for a controlled duration with and without awareness. To ensure the reliability of the awareness manipulation, awareness was monitored on a trial-by-trial basis. Our results show that under these conditions the mere exposure effect does not occur without conscious awareness. In contrast, only when participants were aware of the stimuli did exposure increase liking and recognition. Together these data are consistent with the idea that the mere exposure effect requires conscious awareness and has important implications for theories of memory and affect.

Non-genetic heterogeneity, criticality and cell differentiation.

Science.gov (United States)

Pal, Mainak; Ghosh, Sayantari; Bose, Indrani

2014-11-27

The different cell types in a living organism acquire their identity through the process of cell differentiation in which multipotent progenitor cells differentiate into distinct cell types. Experimental evidence and analysis of large-scale microarray data establish the key role played by a two-gene motif in cell differentiation in a number of cell systems. The two genes express transcription factors which repress each other's expression and autoactivate their own production. A number of theoretical models have recently been proposed based on the two-gene motif to provide a physical understanding of how cell differentiation occurs. In this paper, we study a simple model of cell differentiation which assumes no cooperativity in the regulation of gene expression by the transcription factors. The latter repress each other's activity directly through DNA binding and indirectly through the formation of heterodimers. We specifically investigate how deterministic processes combined with stochasticity contribute in bringing about cell differentiation. The deterministic dynamics of our model give rise to a supercritical pitchfork bifurcation from an undifferentiated stable steady state to two differentiated stable steady states. The stochastic dynamics of our model are studied using the approaches based on the Langevin equations and the linear noise approximation. The simulation results provide a new physical understanding of recent experimental observations. We further propose experimental measurements of quantities like the variance and the lag-1 autocorrelation function in protein fluctuations as the early signatures of an approaching bifurcation point in the cell differentiation process.

Non-daily pre-exposure prophylaxis for HIV prevention

Science.gov (United States)

Anderson, Peter L.; García-Lerma, J. Gerardo; Heneine, Walid

2015-01-01

Purpose of review To discuss non-daily pre-exposure prophylaxis (PrEP) modalities that may provide advantages compared with daily PrEP in cost and cumulative toxicity, but may have lower adherence forgiveness. Recent Findings Animal models have informed our understanding of early viral transmission events, which help guide event-driven PrEP dosing strategies. These models indicate early establishment of viral replication in rectal or cervicovaginal tissues, so event-driven PrEP should rapidly deliver high mucosal drug concentrations within hours of the potential exposure event. Macaque models have demonstrated the high biological efficacy for event-driven dosing of oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) against both vaginal and rectal virus transmission. In humans, the IPERGAY study demonstrated 86% efficacy for event-driven oral TDF/FTC dosing among men who have sex with men (MSM), while no similar efficacy data are available on women or heterosexual men. The HPTN 067 study showed that certain MSM populations adhere well to non-daily PrEP while other populations of women adhere more poorly to non-daily versus daily regimens. Pharmacokinetic studies following oral TDF/FTC dosing in humans, indicate that TFV-diphosphate (the active form of TFV) accumulates to higher concentrations in rectal versus cervicovaginal tissue but non-adherence in trials complicates the interpretation of differential mucosal drug concentrations. Summary Event-driven dosing for TFV-based PrEP has promise for HIV prevention in MSM. Future research of event-driven PrEP in women and heterosexual men should be guided by a better understanding of the importance of mucosal drug concentrations for PrEP efficacy and its sensitivity to adherence. PMID:26633641

Phthalate-induced toxicity: Identifying the vulnerable pathways during sexual differentiation in the male rat

Science.gov (United States)

Human exposures to phthalate ester plasticizer compounds are widespread. Studies in rodents have demonstrated that in utero exposure to various phthalates throughout sexual differentiation (GD14-18) results in decreased fetal testicular androgen production, and ultimately leads t...

Product and Quotient Rules from Logarithmic Differentiation

Science.gov (United States)

Chen, Zhibo

2012-01-01

A new application of logarithmic differentiation is presented, which provides an alternative elegant proof of two basic rules of differentiation: the product rule and the quotient rule. The proof can intrigue students, help promote their critical thinking and rigorous reasoning and deepen their understanding of previously encountered concepts. The…

Adolescents' exposure to sexy media does not hasten the initiation of sexual intercourse.

Science.gov (United States)

Steinberg, Laurence; Monahan, Kathryn C

2011-03-01

It is widely believed that exposure to sexy content in the mass media leads teenagers to become sexually active. Although most research linking sexy media exposure to adolescents' sexual behavior is cross-sectional, several recent, well-publicized longitudinal studies purport to find a causal connection, which has alarmed the public and prompted criticism of the entertainment industry for its corrupting influence on youth. One problem in research on media effects on sexual activity, however, is that outcomes that are presumed to result from media exposure may actually be due to factors that differentially predispose adolescents to have different degrees of media exposure and are themselves related to sexual activity. We reanalyzed data from one of these longitudinal studies (Brown et al., 2006) using propensity score matching to control for preexisting differences between adolescents with and without high exposure to sexy media. With such controls for differential selection in place, we found no evidence that the initiation of sexual intercourse is hastened by exposure to sexy media. PsycINFO Database Record (c) 2011 APA, all rights reserved.

Children exposed to intimate partner violence: Identifying differential effects of family environment on children's trauma and psychopathology symptoms through regression mixture models.

Science.gov (United States)

McDonald, Shelby Elaine; Shin, Sunny; Corona, Rosalie; Maternick, Anna; Graham-Bermann, Sandra A; Ascione, Frank R; Herbert Williams, James

2016-08-01

The majority of analytic approaches aimed at understanding the influence of environmental context on children's socioemotional adjustment assume comparable effects of contextual risk and protective factors for all children. Using self-reported data from 289 maternal caregiver-child dyads, we examined the degree to which there are differential effects of severity of intimate partner violence (IPV) exposure, yearly household income, and number of children in the family on posttraumatic stress symptoms (PTS) and psychopathology symptoms (i.e., internalizing and externalizing problems) among school-age children between the ages of 7-12 years. A regression mixture model identified three latent classes that were primarily distinguished by differential effects of IPV exposure severity on PTS and psychopathology symptoms: (1) asymptomatic with low sensitivity to environmental factors (66% of children), (2) maladjusted with moderate sensitivity (24%), and (3) highly maladjusted with high sensitivity (10%). Children with mothers who had higher levels of education were more likely to be in the maladjusted with moderate sensitivity group than the asymptomatic with low sensitivity group. Latino children were less likely to be in both maladjusted groups compared to the asymptomatic group. Overall, the findings suggest differential effects of family environmental factors on PTS and psychopathology symptoms among children exposed to IPV. Implications for research and practice are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Understanding mechanisms and the role of differentiation in pathogenesis of Toxoplasma gondii: a review

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William J Sullivan Jr

2009-03-01

Full Text Available Parasite differentiation from proliferating tachyzoites into latent bradyzoites is central to pathogenesis and transmission of the intracellular protozoan pathogen Toxoplasma gondii. The presence of bradyzoite-containing cysts in human hosts and their subsequent rupture can cause life-threatening recrudescence of acute infection in the immunocompromised and cyst formation in other animals contributes to zoonotic transmission and widespread dissemination of the parasite. In this review, we discuss the evidence showing how the clinically relevant process of bradyzoite differentiation is regulated at both transcriptional and post-transcriptional levels. Specific regulatory factors implicated in modulating bradyzoite differentiation include promoter-based cis-elements, epigenetic modifications and protein translation control through eukaryotic initiation factor -2 (eIF2. In addition to a summary of the current state of knowledge in these areas we discuss the pharmacological ramifications and pose some questions for future research.

Secondary Traumatization and Differentiation Among the Wives of Former POWs

DEFF Research Database (Denmark)

Lahav, Yael; Levin, Yafit; Bensimon, Moshe

2017-01-01

Repercussions of war captivity may transmit to spouses of former prisoners of war (POW) via posttraumatic stress symptoms (PTSS). Overidentification with their partners underlies the PTSS experienced by former wives of POWs, thus implying impaired self-differentiation. Although wives’ indirect...... of indirect exposure to captivity in the association between husbands’ PTSS and wives’ PTSS and differentiation; and (b) the directionality of the association between wives' differentiation and PTSS over time. The wives of both former POWs (n = 143) and combatants (n = 102) were assessed 30 (T1) and 38 (T2...

Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells.

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Miguel A Brieño-Enríquez

Full Text Available In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation.

Ordinary differential equations

CERN Document Server

Cox, William

1995-01-01

Building on introductory calculus courses, this text provides a sound foundation in the underlying principles of ordinary differential equations. Important concepts, including uniqueness and existence theorems, are worked through in detail and the student is encouraged to develop much of the routine material themselves, thus helping to ensure a solid understanding of the fundamentals required.The wide use of exercises, problems and self-assessment questions helps to promote a deeper understanding of the material and it is developed in such a way that it lays the groundwork for further

Understanding Racial Differences in Exposure to Violent Areas: Integrating Survey, Smartphone, and Administrative Data Resources.

Science.gov (United States)

Browning, Christopher R; Calder, Catherine A; Ford, Jodi L; Boettner, Bethany; Smith, Anna L; Haynie, Dana

2017-01-01

Emerging evidence indicates that exposure to violent areas may influence youth wellbeing. We employ smartphone GPS data on youth activity spaces to examine the extent of, and potential explanations for, racial disparities in these exposures. Multilevel models of data from the Adolescent Health and Development in Context study indicate that exposures to violent areas vary significantly across days of the week and between youth who reside in the same neighborhood. African American youth are exposed to areas with substantially higher levels of violence. Residing in a disadvantaged neighborhood is significantly associated with exposure to violent areas and explains a non-trivial proportion of the racial difference in this outcome. However, neighborhood factors are incomplete explanations of the racial disparity. Characteristics of the activity locations at which youth spend time explain the residual racial disparity in exposure to violent areas. These findings highlight the importance of youth activity spaces, above and beyond their neighborhood environments.

Maintenance of DNA repair capacity in differentiating rat muscle cells in vitro

International Nuclear Information System (INIS)

Koval, T.M.; Kaufman, S.J.

1981-01-01

Unscheduled DNA synthesis was measured at several times during the differentiation of cultured rat skeletal muscle cells in response to exposures to 254 nm UV light. There was no change in the amount of repair DNA synthesis as the cells fuse and differentiate from postmitotic prefusion myoblasts to multinucleated contracting myotubes. (author)

ROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulation

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Maricela Maldonado

2016-09-01

Full Text Available Robust control of human induced pluripotent stem cell (hIPSC differentiation is essential to realize its patient-tailored therapeutic potential. Here, we demonstrate a novel application of Y-27632, a small molecule Rho-associated protein kinase (ROCK inhibitor, to significantly influence the differentiation of hIPSCs in a lineage-specific manner. The application of Y-27632 to hIPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration and time-dependent manner. Such changes in cell and colony morphology were associated with decreased expression of E-cadherin, a cell-cell junctional protein, proportional to the increased exposure to Y-27632. Interestingly, gene and protein expression of pluripotency markers such as NANOG and OCT4 were not downregulated by an exposure to Y-27632 up to 36 h. Simultaneously, epithelial-to-mesenchymal (EMT transition markers were upregulated with an exposure to Y-27632. These EMT-like changes in the cells with longer exposure to Y-27632 resulted in a significant increase in the subsequent differentiation efficiency towards mesendodermal lineage. In contrast, an inhibitory effect was observed when cells were subjected to ectodermal differentiation after prolonged exposure to Y-27632. Collectively, these results present a novel method for priming hIPSCs to modulate their differentiation potential with a simple application of Y-27632.

Suppressed osteoclast differentiation at the chondro-osseous junction mediates endochondral ossification retardation in long bones of Wistar fetal rats with prenatal ethanol exposure

Energy Technology Data Exchange (ETDEWEB)

Pan, Zhengqi [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Zhang, Xianrong [Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China); Shangguan, Yangfan; Hu, Hang [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)

2016-08-15

Prenatal ethanol exposure (PEE) inhibits longitudinal growth of fetal bones, but the underlying mechanisms remain unknown. In this study, we aimed to investigate how PEE induces the retardation of long bone development in fetal rats. Pregnant Wistar rats were treated with ethanol or distilled water (control group) by gavage from gestational day (GD) 9 to 20. Fetuses were delivered by cesarean section on GD20. Fetal sera were collected for assessing corticosterone (CORT) level. Fetal long bones were harvested for histochemical, immunohistochemical and gene expression analysis. Primary chondrocytes were treated with ethanol or CORT for analyzing genes expression. PEE fetuses showed a significant reduction in birth weight and body length. The serum CORT concentration in PEE group was significantly increased, while the body weight, body length and femur length all were significantly decreased in the PEE group. The length of the epiphyseal hypertrophy zone was enlarged, whereas the length of the primary ossification center was significantly reduced in PEE fetuses. TUNEL assay showed reduced apoptosis in the PEE group. Further, the gene expression of osteoprotegerin (OPG) was markedly up-regulated. In vitro experiments showed that CORT (but not ethanol) treatment significantly activated the expression of OPG, while the application of glucocorticoid receptor inhibitor, mifepristone, attenuated these change induced by CORT. These results indicated that PEE-induced glucocorticoid over-exposure enhanced the expression of OPG in fetal epiphyseal cartilage and further lead to the suppressed osteoclast differentiation in the chondro-osseous junction and consequently inhibited the endochondral ossification in long bones of fetal rats. - Highlights: • Glucocorticoid but not ethanol enhanced the expression of OPG in chondrocytes. • PEE reduced osteoclast differentiation relative with over-expression of OPG. • PEE inhibited endochondral ossification in fetal long bones of

Contaminant exposure in terrestrial vertebrates

International Nuclear Information System (INIS)

Smith, Philip N.; Cobb, George P.; Godard-Codding, Celine; Hoff, Dale; McMurry, Scott T.; Rainwater, Thomas R.; Reynolds, Kevin D.

2007-01-01

Here we review mechanisms and factors influencing contaminant exposure among terrestrial vertebrate wildlife. There exists a complex mixture of biotic and abiotic factors that dictate potential for contaminant exposure among terrestrial and semi-terrestrial vertebrates. Chemical fate and transport in the environment determine contaminant bioaccessibility. Species-specific natural history characteristics and behavioral traits then play significant roles in the likelihood that exposure pathways, from source to receptor, are complete. Detailed knowledge of natural history traits of receptors considered in conjunction with the knowledge of contaminant behavior and distribution on a site are critical when assessing and quantifying exposure. We review limitations in our understanding of elements of exposure and the unique aspects of exposure associated with terrestrial and semi-terrestrial taxa. We provide insight on taxa-specific traits that contribute, or limit exposure to, transport phenomenon that influence exposure throughout terrestrial systems, novel contaminants, bioavailability, exposure data analysis, and uncertainty associated with exposure in wildlife risk assessments. Lastly, we identify areas related to exposure among terrestrial and semi-terrestrial organisms that warrant additional research. - Both biotic and abiotic factors determine chemical exposure for terrestrial vertebrates

Estimating pediatric general anesthesia exposure: Quantifying duration and risk.

Science.gov (United States)

Bartels, Devan Darby; McCann, Mary Ellen; Davidson, Andrew J; Polaner, David M; Whitlock, Elizabeth L; Bateman, Brian T

2018-05-02

Understanding the duration of pediatric general anesthesia exposure in contemporary practice is important for identifying groups at risk for long general anesthesia exposures and designing trials examining associations between general anesthesia exposure and neurodevelopmental outcomes. We performed a retrospective cohort analysis to estimate pediatric general anesthesia exposure duration during 2010-2015 using the National Anesthesia Clinical Outcomes Registry. A total of 1 548 021 pediatric general anesthetics were included. Median general anesthesia duration was 57 minutes (IQR: 28-86) with 90th percentile 145 minutes. Children aged 3 hours. High ASA physical status and care at a university hospital were associated with longer exposure times. While the vast majority (94%) of children undergoing general anesthesia are exposed for risk for longer exposures. These findings may help guide the design of future trials aimed at understanding neurodevelopmental impact of prolonged exposure in these high-risk groups. © 2018 John Wiley & Sons Ltd.

Oral Exposure of a Child to a Lithium Ion Battery.

Science.gov (United States)

Townsend, Janice A; Curran, Ronald

2016-01-01

Battery exposure has the potential for severe morbidity and possible mortality. Accidental exposure is rising with the increased use of button batteries, and young children and older adults are at highest risk for accidental exposure. The purpose of this paper is to report a case of mouth exposure to a lithium ion battery in a boy. A review of the current literature on incidence, diagnosis, and outcomes of battery exposure is presented. When symptoms such as diarrhea, vomiting, and abdominal distress of non-specific origin are present, battery ingestion should be included in the differential diagnosis. Dentists may be the first health professionals to encounter battery exposure, especially in the case of mouth exposures. Knowledge of signs and symptoms are necessary to properly diagnose and refer for medical management.

Consequences of exposure measurement error for confounder identification in environmental epidemiology

DEFF Research Database (Denmark)

Budtz-Jørgensen, Esben; Keiding, Niels; Grandjean, Philippe

2003-01-01

Non-differential measurement error in the exposure variable is known to attenuate the dose-response relationship. The amount of attenuation introduced in a given situation is not only a function of the precision of the exposure measurement but also depends on the conditional variance of the true...... exposure given the other independent variables. In addition, confounder effects may also be affected by the exposure measurement error. These difficulties in statistical model development are illustrated by examples from a epidemiological study performed in the Faroe Islands to investigate the adverse...

Differential activation of amygdala, dorsal and ventral hippocampus following an exposure to a reminder ofunderwater trauma

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Gilad eRitov

2014-01-01

Full Text Available Recollection of emotional memories is attributed in part to the activation of the amygdala and the hippocampus. Recent hypothesis suggest a pivotal role for the ventral hippocampus in traumatic stress processing and emotional memory retrieval. Persistent re-experiencing and intrusive recollections are core symptoms in acute and posttraumatic stress disorders (ASD; PTSD. Such intrusive recollections are often triggered by reminders associated with the trauma.We examined the impact of exposure to a trauma reminder (under water trauma on the activation of the basolateral amygdala (BLA, dorsal and ventral hippocampus. Rats were exposed to underwater trauma and 24 hours later were re-exposed to the context of the trauma. Phosphorylation of the extracellular signal-regulated kinase (ERK was used as a marker for level of activation of these regions. Significant increase in ERK activation was found in the ventral hippocampus and BLA. Such pattern of activation was not found in animals exposed only to the trauma or in animals exposed only to the trauma reminder. Additionally, the dissociative pattern of activation of the ventral hippocampus sub-regions positively correlated with the activation of the BLA.Our findings suggest a specific pattern of neural activation during recollection of a trauma reminder, with a unique contribution of the ventral hippocampus. Measured 24 hrs after the exposure to the traumatic experience, the current findings relate to relatively early stages of traumatic memory consolidation. Understanding the neural mechanisms underlying these initial stages may contribute to developing intervention strategies that could reduce the risk of eventually developing PTSD.

Differential belongings

DEFF Research Database (Denmark)

Oldrup, Helene

2014-01-01

This paper explores suburban middle-class residents’ narratives about housing choice, everyday life and belonging in residential areas of Greater Copenhagen, Denmark, to understand how residential processes of social differentiation are constituted. Using Savage et al.’s concepts of discursive...... and not only to the area itself. In addition, rather than seeing suburban residential areas as homogenous, greater attention should be paid to differences within such areas....

METHYLMERCURY IMPAIRS NEURONAL DIFFERENTIATION BY ALTERING NEUROTROPHIN SIGNALING.

Science.gov (United States)

In previous in vivo studies, we observed that developmental exposure to CH3Hg can alter neocortical morphology and neurotrophin signaling. Using primed PC12 cells as a model system for neuronal differentiation, we examined the hypothesis that the developmental effects of CH3Hg ma...

Testing and differentiation

DEFF Research Database (Denmark)

Kousholt, Kristine

This presentation will explore how educational standardized testing becomes meaningful/not meaningful for children and teachers and at the same time how testing becomes part of everyday differentiation and categorization processes. The presentation is based on a 3 year long post doc project...... and education. It will be explored how the children in their communities construct understandings of themselves as clever or non-clever in relation to how they participate in test situations and in relation to which result they receive afterwards. Furthermore it will be explored how we might understand...... for help. The presentation will end with considerations on how we might understand the growing need for so-called objective assessment which is assumed to be independent of subjective norms and local context....

ROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulation.

Science.gov (United States)

Maldonado, Maricela; Luu, Rebeccah J; Ramos, Michael E P; Nam, Jin

2016-09-01

Robust control of human induced pluripotent stem cell (hIPSC) differentiation is essential to realize its patient-tailored therapeutic potential. Here, we demonstrate a novel application of Y-27632, a small molecule Rho-associated protein kinase (ROCK) inhibitor, to significantly influence the differentiation of hIPSCs in a lineage-specific manner. The application of Y-27632 to hIPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration and time-dependent manner. Such changes in cell and colony morphology were associated with decreased expression of E-cadherin, a cell-cell junctional protein, proportional to the increased exposure to Y-27632. Interestingly, gene and protein expression of pluripotency markers such as NANOG and OCT4 were not downregulated by an exposure to Y-27632 up to 36h. Simultaneously, epithelial-to-mesenchymal (EMT) transition markers were upregulated with an exposure to Y-27632. These EMT-like changes in the cells with longer exposure to Y-27632 resulted in a significant increase in the subsequent differentiation efficiency towards mesendodermal lineage. In contrast, an inhibitory effect was observed when cells were subjected to ectodermal differentiation after prolonged exposure to Y-27632. Collectively, these results present a novel method for priming hIPSCs to modulate their differentiation potential with a simple application of Y-27632. Copyright © 2016 Helmholtz Zentrum München. Published by Elsevier B.V. All rights reserved.

Environmentally relevant exposure to 17{alpha}-ethinylestradiol affects the telencephalic proteome of male fathead minnows

Energy Technology Data Exchange (ETDEWEB)

Martyniuk, Christopher J., E-mail: cmartyn@unb.ca [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611 (United States); Kroll, Kevin J.; Doperalski, Nicholas J.; Barber, David S.; Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611 (United States)

2010-07-15

Estrogens are key mediators of neuronal processes in vertebrates. As such, xenoestrogens present in the environment have the potential to alter normal central nervous system (CNS) function. The objectives of the present study were (1) to identify proteins with altered abundance in the male fathead minnow telencephalon as a result of low-level exposure to17{alpha}-ethinylestradiol (EE{sub 2}), and (2) to better understand the underlying mechanisms of 17{beta}-estradiol (E{sub 2}) feedback in this important neuroendocrine tissue. Male fathead minnows exposed to a measured concentration of 5.4 ng EE{sub 2}/L for 48 h showed decreased plasma E{sub 2} levels of approximately 2-fold. Of 77 proteins that were quantified statistically, 14 proteins were down-regulated after EE{sub 2} exposure, including four histone proteins, ATP synthase, H+ transporting subunits, and metabolic proteins (lactate dehydrogenase B4, malate dehydrogenase 1b). Twelve proteins were significantly induced by EE{sub 2} including microtubule-associated protein tau (Mapt), astrocytic phosphoprotein, ependymin precursor, and calmodulin. Mapt showed an increase in protein abundance but a decrease in mRNA expression after EE{sub 2} exposure{sub ,} suggesting there may be a negative feedback response in the telencephalon to decreased mRNA transcription with increasing Mapt protein abundance. These results demonstrate that a low, environmentally relevant exposure to EE{sub 2} can rapidly alter the abundance of proteins involved in cell differentiation and proliferation, neuron network morphology, and long-term synaptic potentiation. Together, these findings provide a better understanding of the molecular responses underlying E{sub 2} feedback in the brain and demonstrate that quantitative proteomics can be successfully used in ecotoxicology to characterize affected cellular pathways and endocrine physiology.

Positional cloning of the PIS mutation in goats and its impact on understanding mammalian sex-differentiation

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Pailhoux Eric

2005-12-01

Full Text Available Abstract In goats, the PIS (polled intersex syndrome mutation is responsible for both the absence of horns in males and females and sex-reversal affecting exclusively XX individuals. The mode of inheritance is dominant for the polled trait and recessive for sex-reversal. In XX PIS-/- mutants, the expression of testis-specific genes is observed very precociously during gonad development. Nevertheless, a delay of 4–5 days is observed in comparison with normal testis differentiation in XY males. By positional cloning, we demonstrate that the PIS mutation is an 11.7-kb regulatory-deletion affecting the expression of two genes, PISRT1 and FOXL2 which could act synergistically to promote ovarian differentiation. The transcriptional extinction of these two genes leads, very early, to testis-formation in XX homozygous PIS-/- mutants. According to their expression profiles and bibliographic data, we propose that FOXL2 may be an ovary-differentiating gene, and the non-coding RNA PISRT1, an anti-testis factor repressing SOX9, a key regulator of testis differentiation. Under this hypothesis, SRY, the testis-determining factor would inhibit these two genes in the gonads of XY males, to ensure testis differentiation.

Glu- and Lys-forms of plasminogen differentially affect phosphatidylserine exposure on the platelet surface

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D. D. Zhernossekov

2017-04-01

Full Text Available Plasminogen/plasmin system is known for its ability to support hemostatic balance of blood. However, plasminogen may be considered as an adhesive ligand and in this way could affect the functioning of blood cells. We showed that exogenous Lys-plasminogen, but not its Glu-form, inhibited platelet aggregation and suppressed platelet α-granule secretion. The aim of this work was to investigate the influence of Glu- and Lys-form of plasminogen on the formation of platelet procoagulant surface using phosphatidylserine exposure as a marker. Human platelets were obtained from human platelet-rich plasma (donors were healthy volunteers, men aged 30-40 years by gel-filtration on Sepharose 2B. Phosphatidylserine exposure on the platelet surface was evaluated by flow cytometry with FITC-conjugated annexin A5. Glu- and Lys-plasminogen have different impact on the platelet functioning. Exogenous Lys-plasminogen has no significant effect on phosphatidylserine exposure, while Glu-plasminogen increases phosphatidylserine exposure on the surface of thrombin- and collagen-activated human platelets. Glu-plasminogen can be considered as a co-stimulator of agonist-induced platelet secretion and procoagulant surface formation. Meanwhile effects of Lys-plasminogen are probably directed at platelet-platelet interactions and not related to agonist-stimulated pro-apoptotic changes. The observed different effects of Glu- and Lys-plasminogen on phosphatidylserine exposure can be explained by their structural peculiarities.

Non-instantaneous impulses in differential equations

CERN Document Server

Agarwal, Ravi; O'Regan, Donal

2017-01-01

This monograph is the first published book devoted to the theory of differential equations with non-instantaneous impulses. It aims to equip the reader with mathematical models and theory behind real life processes in physics, biology, population dynamics, ecology and pharmacokinetics. The authors examine a wide scope of differential equations with non-instantaneous impulses through three comprehensive chapters, providing an all-rounded and unique presentation on the topic, including: - Ordinary differential equations with non-instantaneous impulses (scalar and n-dimensional case) - Fractional differential equa tions with non-instantaneous impulses (with Caputo fractional derivatives of order q ϵ (0, 1)) - Ordinary differential equations with non-instantaneous impulses occurring at random moments (with exponential, Erlang, or Gamma distribution) Each chapter focuses on theory, proofs and examples, and contains numerous graphs to enrich the reader’s understanding. Additionally, a carefully selected bibliogr...

TCDD alters medial epithelial cell differentiation during palatogenesis

International Nuclear Information System (INIS)

Abbott, B.D.; Birnbaum, L.S.

1989-01-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widely distributed, persistent environmental contaminant that is teratogenic in mice, where it induces hydronephrosis and cleft palate. The incidence of clefting has been shown to be dose dependent after exposure on either gestation Day (GD) 10 or 12, although the embryo is more susceptible on GD 12. TCDD-exposed palatal shelves meet but do not fuse, and programmed cell death of the medial epithelial cells is inhibited. The mechanism of action through which TCDD alters the program of medial cell development has not been examined in earlier studies, and it is not known whether the mechanism is the same regardless of the dose or developmental stage of exposure. In this study, C57BL/6N mice, a strain sensitive to TCDD, were dosed orally on GD 10 or 12 with 0, 6, 12, 24, or 30 micrograms/kg body wt, in 10 ml corn oil/kg. Embryonic palatal shelves were examined on GD 14, 15, or 16. The degree of palatal closure, epithelial surface morphology, and cellular ultrastructure, the incorporation of [3H]TdR, the expression of EGF receptors, and the binding of 125I-EGF were assessed. After exposure on GD 10 or 12, TCDD altered the differentiation pathway of the medial epithelial cells. The palatal shelves were of normal size and overall morphology, but fusion of the medial epithelia of the opposing shelves did not occur. TCDD prevented programmed cell death of the medial peridermal cells. The expression of EGF receptors by medial cells continued through Day 16 and the receptors were able to bind ligand. The medial cells differentiated into a stratified, squamous, keratinizing epithelium. The shift in phenotype to an oral-like epithelium occurred after exposure on either GD 10 or 12. At the lower dose (6 micrograms/kg), fewer cleft palates were produced, but those shelves which did respond had a fully expressed shift in differentiation

Pediatric Death Due to Myocarditis After Exposure to Cannabis

Directory of Open Access Journals (Sweden)

Thomas M. Nappe

2017-03-01

Full Text Available Since marijuana legalization, pediatric exposures to cannabis have increased. 1 To date, pediatric deaths from cannabis exposure have not been reported. The authors report an 11-month-old male who, following cannabis exposure, presented with central nervous system depression after seizure, and progressed to cardiac arrest and died. Myocarditis was diagnosed post-mortem and cannabis exposure was confirmed. Given the temporal relationship of these two rare occurrences – cannabis exposure and sudden death secondary to myocarditis in an 11-month-old – as well as histological consistency with drug-induced myocarditis without confirmed alternate causes, and prior reported cases of cannabis-associated myocarditis, a possible relationship exists between cannabis exposure in this child and myocarditis leading to death. In areas where marijuana is commercially available or decriminalized, the authors urge clinicians to preventively counsel parents and to include cannabis exposure in the differential diagnosis of patients presenting with myocarditis.

Development of retrospective quantitative and qualitative job-exposure matrices for exposures at a beryllium processing facility.

Science.gov (United States)

Couch, James R; Petersen, Martin; Rice, Carol; Schubauer-Berigan, Mary K

2011-05-01

To construct a job-exposure matrix (JEM) for an Ohio beryllium processing facility between 1953 and 2006 and to evaluate temporal changes in airborne beryllium exposures. Quantitative area- and breathing-zone-based exposure measurements of airborne beryllium were made between 1953 and 2006 and used by plant personnel to estimate daily weighted average (DWA) exposure concentrations for sampled departments and operations. These DWA measurements were used to create a JEM with 18 exposure metrics, which was linked to the plant cohort consisting of 18,568 unique job, department and year combinations. The exposure metrics ranged from quantitative metrics (annual arithmetic/geometric average DWA exposures, maximum DWA and peak exposures) to descriptive qualitative metrics (chemical beryllium species and physical form) to qualitative assignment of exposure to other risk factors (yes/no). Twelve collapsed job titles with long-term consistent industrial hygiene samples were evaluated using regression analysis for time trends in DWA estimates. Annual arithmetic mean DWA estimates (overall plant-wide exposures including administration, non-production, and production estimates) for the data by decade ranged from a high of 1.39 μg/m(3) in the 1950s to a low of 0.33 μg/m(3) in the 2000s. Of the 12 jobs evaluated for temporal trend, the average arithmetic DWA mean was 2.46 μg/m(3) and the average geometric mean DWA was 1.53 μg/m(3). After the DWA calculations were log-transformed, 11 of the 12 had a statistically significant (p < 0.05) decrease in reported exposure over time. The constructed JEM successfully differentiated beryllium exposures across jobs and over time. This is the only quantitative JEM containing exposure estimates (average and peak) for the entire plant history.

Differential Exposure to Early Childhood Education Services and Mother-Toddler Interaction

Science.gov (United States)

Klebanov, P.K.; Brooks-Gunn, J.

2008-01-01

This study examined the associations of exposure to early childhood education (ECE) services upon 2.5-year-old children's task persistence and enthusiasm and their mothers' authoritative and authoritarian behavior and support stimulation. Families participated in the Infant Health and Development Program, an eight-site randomized comprehensive ECE…

The effect of shorter exposure versus prolonged exposure on treatment outcome in Tourette syndrome and chronic tic disorders - an open trial.

Science.gov (United States)

van de Griendt, Jolande M T M; van Dijk, Maarten K; Verdellen, Cara W J; Verbraak, Marc J P M

2018-01-11

Exposure and response prevention has shown to be an effective strategy and is considered a first-line intervention in the behavioural treatment of tic disorders. Prior research demonstrated significant tic reduction after 12 two hour sessions. In this open trial, the question is addressed whether, relative to these prolonged sessions, exposure sessions of shorter duration yield differential outcome for patients with tic disorders. A total of 29 patients diagnosed with Tourette syndrome (TS) or chronic tic disorder were treated with shorter exposure sessions (1 h), and these data were compared to the data from a study about prolonged exposure (2 h, n = 21). Outcome was measured by the Yale Global Tic Severity Scale (YGTSS). Results suggest that after taking the difference in illness duration between the two groups into account, the effectiveness of shorter exposure sessions is not inferior to that of prolonged exposure. Results suggest that treatment with shorter exposure might be more efficient and more patients can be reached. Future research is needed to gain more insight into the mechanisms underlying the efficacy of behavioural treatments for tics.

Understanding Arsenic Dynamics in Agronomic Systems to ...

Science.gov (United States)

This review is on arsenic in agronomic systems, and covers processes that influence the entry of arsenic into the human food supply. The scope is from sources of arsenic (natural and anthropogenic) in soils, biogeochemical and rhizosphere processes that control arsenic speciation and availability, through to mechanisms of uptake by crop plants and potential mitigation strategies. This review makes a case for taking steps to prevent or limit crop uptake of arsenic, wherever possible, and to work toward a long-term solution to the presence of arsenic in agronomic systems. The past two decades have seen important advances in our understanding of how biogeochemical and physiological processes influence human exposure to soil arsenic, and thus must now prompt an informed reconsideration and unification of regulations to protect the quality of agricultural and residential soils. Consumption of staple foods such as rice, beverages such as apple juice, or vegetables grown in historically arsenic-contaminated soils is now recognized as a tangible route of arsenic exposure that, in many cases, is more significant than exposure from drinking water. Understanding the sources of arsenic to crop plants and the factors that influence them is key to reducing exposure now and preventing exposure in future. In addition to the abundant natural sources of arsenic, there are a large number of industrial and agricultural sources of arsenic to the soil; from mining wastes, coal fly

Extracellular matrix aggregates from differentiating embryoid bodies as a scaffold to support ESC proliferation and differentiation.

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Saik-Kia Goh

Full Text Available Embryonic stem cells (ESCs have emerged as potential cell sources for tissue engineering and regeneration owing to its virtually unlimited replicative capacity and the potential to differentiate into a variety of cell types. Current differentiation strategies primarily involve various growth factor/inducer/repressor concoctions with less emphasis on the substrate. Developing biomaterials to promote stem cell proliferation and differentiation could aid in the realization of this goal. Extracellular matrix (ECM components are important physiological regulators, and can provide cues to direct ESC expansion and differentiation. ECM undergoes constant remodeling with surrounding cells to accommodate specific developmental event. In this study, using ESC derived aggregates called embryoid bodies (EB as a model, we characterized the biological nature of ECM in EB after exposure to different treatments: spontaneously differentiated and retinoic acid treated (denoted as SPT and RA, respectively. Next, we extracted this treatment-specific ECM by detergent decellularization methods (Triton X-100, DOC and SDS are compared. The resulting EB ECM scaffolds were seeded with undifferentiated ESCs using a novel cell seeding strategy, and the behavior of ESCs was studied. Our results showed that the optimized protocol efficiently removes cells while retaining crucial ECM and biochemical components. Decellularized ECM from SPT EB gave rise to a more favorable microenvironment for promoting ESC attachment, proliferation, and early differentiation, compared to native EB and decellularized ECM from RA EB. These findings suggest that various treatment conditions allow the formulation of unique ESC-ECM derived scaffolds to enhance ESC bioactivities, including proliferation and differentiation for tissue regeneration applications.

Basic linear partial differential equations

CERN Document Server

Treves, Francois

1975-01-01

Focusing on the archetypes of linear partial differential equations, this text for upper-level undergraduates and graduate students features most of the basic classical results. The methods, however, are decidedly nontraditional: in practically every instance, they tend toward a high level of abstraction. This approach recalls classical material to contemporary analysts in a language they can understand, as well as exploiting the field's wealth of examples as an introduction to modern theories.The four-part treatment covers the basic examples of linear partial differential equations and their

Effects of trichostatins on differentiation of murine erythroleukemia cells

International Nuclear Information System (INIS)

Yoshida, M.; Nomura, S.; Beppu, T.

1987-01-01

The fungistatic antibiotics trichostatins (TS) A and C were isolated from culture broth of Streptomyces platensis No. 145 and were found to be potent inducers of differentiation in murine erythroleukemia (Friend and RV133) cells at concentrations of 1.5 X 10(-8) M for TSA and 5 X 10(-7) M for TSC. Differentiation induced by TS was cooperatively enhanced by UV irradiation but not by treatment with dimethyl sulfoxide. This enhanced activity was completely inhibited by adding cycloheximide to the culture medium 2 h after exposure to TS, suggesting that TS are dimethyl sulfoxide-type inducers of erythroid differentiation. No inhibitory effect of TS was observed on macromolecular synthesis in cultured cells

PPARγ isoforms differentially regulate metabolic networks to mediate mouse prostatic epithelial differentiation.

Science.gov (United States)

Strand, D W; Jiang, M; Murphy, T A; Yi, Y; Konvinse, K C; Franco, O E; Wang, Y; Young, J D; Hayward, S W

2012-08-09

Recent observations indicate prostatic diseases are comorbidities of systemic metabolic dysfunction. These discoveries revealed fundamental questions regarding the nature of prostate metabolism. We previously showed that prostate-specific ablation of PPARγ in mice resulted in tumorigenesis and active autophagy. Here, we demonstrate control of overlapping and distinct aspects of prostate epithelial metabolism by ectopic expression of individual PPARγ isoforms in PPARγ knockout prostate epithelial cells. Expression and activation of either PPARγ 1 or 2 reduced de novo lipogenesis and oxidative stress and mediated a switch from glucose to fatty acid oxidation through regulation of genes including Pdk4, Fabp4, Lpl, Acot1 and Cd36. Differential effects of PPARγ isoforms included decreased basal cell differentiation, Scd1 expression and triglyceride fatty acid desaturation and increased tumorigenicity by PPARγ1. In contrast, PPARγ2 expression significantly increased basal cell differentiation, Scd1 expression and AR expression and responsiveness. Finally, in confirmation of in vitro data, a PPARγ agonist versus high-fat diet (HFD) regimen in vivo confirmed that PPARγ agonization increased prostatic differentiation markers, whereas HFD downregulated PPARγ-regulated genes and decreased prostate differentiation. These data provide a rationale for pursuing a fundamental metabolic understanding of changes to glucose and fatty acid metabolism in benign and malignant prostatic diseases associated with systemic metabolic stress.

Osteogenic differentiation of MC3T3-E1 cells on poly(L-lactide)/Fe{sub 3}O{sub 4} nanofibers with static magnetic field exposure

Energy Technology Data Exchange (ETDEWEB)

Cai, Qing [State Key Laboratory of Organic–inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 (China); Shi, Yuzhou; Shan, Dingying; Jia, Wenkai; Duan, Shun [Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 (China); Deng, Xuliang [Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081 (China); Yang, Xiaoping, E-mail: yangxp@mail.buct.edu.cn [State Key Laboratory of Organic–inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 (China)

2015-10-01

Proliferation and differentiation of bone-related cells are modulated by many factors such as scaffold design, growth factor, dynamic culture system, and physical simulation. Nanofibrous structure and moderate-intensity (1 mT–1 T) static magnetic field (SMF) have been identified as capable of stimulating proliferation and differentiation of osteoblasts. Herein, magnetic nanofibers were prepared by electrospinning mixture solutions of poly(L-lactide) (PLLA) and ferromagnetic Fe{sub 3}O{sub 4} nanoparticles (NPs). The PLLA/Fe{sub 3}O{sub 4} composite nanofibers demonstrated homogeneous dispersion of Fe{sub 3}O{sub 4} NPs, and their magnetism depended on the contents of Fe{sub 3}O{sub 4} NPs. SMF of 100 mT was applied in the culture of MC3T3-E1 osteoblasts on pure PLLA and PLLA/Fe{sub 3}O{sub 4} composite nanofibers for the purpose of studying the effect of SMF on osteogenic differentiation of osteoblastic cells on magnetic nanofibrous scaffolds. On non-magnetic PLLA nanofibers, the application of external SMF could enhance the proliferation and osteogenic differentiation of MC3T3-E1 cells. In comparison with pure PLLA nanofibers, the incorporation of Fe{sub 3}O{sub 4} NPs could also promote the proliferation and osteogenic differentiation of MC3T3-E1 cells in the absence or presence of external SMF. The marriage of magnetic nanofibers and external SMF was found most effective in accelerating every aspect of biological behaviors of MC3T3-E1 osteoblasts. The findings demonstrated that the magnetic feature of substrate and microenvironment were applicable ways in regulating osteogenesis in bone tissue engineering. - Highlights: • Magnetic nanofibers containing well-dispersed Fe{sub 3}O{sub 4} nanoparticles were produced. • Static magnetic field (SMF) was applied to perform the culture of osteoblasts. • Osteogenic differentiation was enhanced on magnetic substrate with exposure to SMF.

Introduction to computation and modeling for differential equations

CERN Document Server

Edsberg, Lennart

2008-01-01

An introduction to scientific computing for differential equationsIntroduction to Computation and Modeling for Differential Equations provides a unified and integrated view of numerical analysis, mathematical modeling in applications, and programming to solve differential equations, which is essential in problem-solving across many disciplines, such as engineering, physics, and economics. This book successfully introduces readers to the subject through a unique ""Five-M"" approach: Modeling, Mathematics, Methods, MATLAB, and Multiphysics. This approach facilitates a thorough understanding of h

Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks.

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Elizabeth A Osterndorff-Kahanek

Full Text Available Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY, nucleus accumbens (NAC, prefrontal cortex (PFC, and liver after four weekly cycles of chronic intermittent ethanol (CIE vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000 at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600. Within each region, there was little gene overlap across time (~20%. All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global 'rewiring' of coexpression systems involving glial and immune signaling as well as neuronal genes.

Differential geometry connections, curvature, and characteristic classes

CERN Document Server

Tu, Loring W

2017-01-01

This text presents a graduate-level introduction to differential geometry for mathematics and physics students. The exposition follows the historical development of the concepts of connection and curvature with the goal of explaining the Chern–Weil theory of characteristic classes on a principal bundle. Along the way we encounter some of the high points in the history of differential geometry, for example, Gauss' Theorema Egregium and the Gauss–Bonnet theorem. Exercises throughout the book test the reader’s understanding of the material and sometimes illustrate extensions of the theory. Initially, the prerequisites for the reader include a passing familiarity with manifolds. After the first chapter, it becomes necessary to understand and manipulate differential forms. A knowledge of de Rham cohomology is required for the last third of the text. Prerequisite material is contained in author's text An Introduction to Manifolds, and can be learned in one semester. For the benefit of the reader and to establ...

Construction and identification of differential expression genes of peripheral blood cells in radon-exposed mice

International Nuclear Information System (INIS)

Chen Rui; Shi Minhua; Hu Huacheng; Li Jianxiang; Nie Jihua; Tong Jian

2009-01-01

Objective: To screen and identify the differential expression genes on peripheral blood cells of mice based on the experimental animal model of radon exposure. Methods: BALB/c mice were exposed in a type HD-3 multifunctional radon-room, with the accumulative doses of radon-exposure group at 105 WLM and control group at 1 WLM. Total RNA was extracted from peripheral blood cells and the methods of SMART for dscDNA synthesis and SSH for gene screening was applied. With the construction of the cDNA library enriched with differentially expressed genes, the pMD 18-T plasmid containing LacZ operator at the multiple cloning site was used to allow a blue-white screening. The TA clones were amplified by nested PCR and the reverse Northern blot was used to identify up and down regulation of the clones. The differently expressed cDNA was then sequenced and analyzed. Results: The subtracted cDNA libraries were successfully constructed. A total of 390 recombinant white colonies were randomly selected. Among the 312 cDNA monoclones selected from both forward- and reverse-subtracted libraries, 41 clones were chosen to sequence for their differential expressions based on reverse Northern blot. Among the 41 sequenced clones, 10 clones with known function/annotation and 3 new ESTs with the GenBank accession numbers were obtained. Most of the known function/annotation genes were revealed to be related with cell proliferation, metabolism, cellular apoptosis and carcinogenesis. Conclusions: The animal model of radon exposure was established and the cDNA library of peripheral blood cells was successfully constructed. Radon exposure could up- and down-regulate a series of genes. Differentially expressed genes could be identified by using SSH technique and the results may help exploring mechanisms of random exposure. (authors)

In ovo exposure to o,p -DDE affects sexual development but not sexual differentiation in Japanese medaka (Oryzias latipes).

Science.gov (United States)

Papoulias, D.M.; Villalobos, Sergio A.; Meadows, J.; Noltie, Douglas B.; Giesy, J.P.; Tillitt, D.E.

2003-01-01

Despite being banned in many countries, dichlorodiphenyltrichloroethane (DDT) and its metabolites dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD) continue to be found in fish tissues at concentrations of concern. Like o,p -DDT, o,p -DDE is estrogenic and is believed to exert its effects through binding to the estrogen receptor. The limited toxicologic data for o,p -DDE suggest that it decreases fecundity and fertility of fishes. We conducted an egg injection study using the d-rR strain of medaka and environmentally relevant concentrations of o,p -DDE to examine its effects on sexual differentiation and development. The gonads of exposed fish showed no evidence of sex reversal or intersex. However, other gonad abnormalities occurred in exposed individuals. Females exhibited few vitellogenic oocytes and increased atresia. Male testes appeared morphologically normal but were very small. Gonadosomatic index values for both sexes were lower for exposed fish. Our observations of abnormal female and very small male gonads after in ovo o,p -DDE exposure may be indicative of effects on early endocrine processes important for normal ovarian and testicular development.

Developmental exposure to fluoxetine modulates the serotonin system in hypothalamus.

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Cecilia Berg

Full Text Available The selective serotonin reuptake inhibitor (SSRI fluoxetine (FLU, Prozac® is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.

Peripheral blood signatures of lead exposure.

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Heather G LaBreche

Full Text Available BACKGROUND: Current evidence indicates that even low-level lead (Pb exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. METHODOLOGY/PRINCIPAL FINDING: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. CONCLUSIONS/SIGNIFICANCE: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway.

Clustering of Sun Exposure Measurements

OpenAIRE

Have, Anna Szynkowiak; Larsen, Jan; Hansen, Lars Kai; Philipsen, Peter Alshede; Thieden, Elisabeth; Wulf, Hans Christian

2002-01-01

In a medically motivated Sun-exposure study, questionnaires concerning Sun-habits were collected from a number of subjects together with UV radiation measurements. This paper focuses on identifying clusters in the heterogeneous set of data for the purpose of understanding possible relations between Sun-habits exposure and eventually assessing the risk of skin cancer. A general probabilistic framework originally developed for text and Web mining is demonstrated to be useful for clustering of b...

Use of different exposure metrics for understanding multi-modal travel injury risk

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S. Ilgin Guler

2016-08-01

Full Text Available The objective of this work is to identify characteristics of different metrics of exposure for quantifying multi-modal travel injury risk. First, a discussion on the use of time-based and trip-based metrics for road user exposure to injury risk, considering multiple travel modes, is presented. The main difference between a time-based and trip-based metric is argued to be that a time-based metric reflects the actual duration of time spent on the road exposed to the travel risks. This can be proven to be important when considering multiple modes since different modes typically different speeds and average travel distances. Next, the use of total number of trips, total time traveled, and mode share (time-based or trip-based is considered to compare the injury risk of a given mode at different locations. It is argued that using mode share the safety concept which focuses on absolute numbers can be generalized. Quantitative results are also obtained from combining travel survey data with police collision reports for ten counties in California. The data are aggregated for five modes: (i cars, (ii SUVs, (iii transit riders, (iv bicyclists, and (v pedestrians. These aggregated data are used to compare travel risk of different modes with time-based or trip-based exposure metrics. These quantitative results confirm the initial qualitative discussions. As the penetration of mobile probes for transportation data collection increases, the insights of this study can provide guidance on how to best utilize the added value of such data to better quantify travel injury risk, and improve safety.

Selective neuronal differentiation of neural stem cells induced by nanosecond microplasma agitation.

Science.gov (United States)

Xiong, Z; Zhao, S; Mao, X; Lu, X; He, G; Yang, G; Chen, M; Ishaq, M; Ostrikov, K

2014-03-01

An essential step for therapeutic and research applications of stem cells is their ability to differentiate into specific cell types. Neuronal cells are of great interest for medical treatment of neurodegenerative diseases and traumatic injuries of central nervous system (CNS), but efforts to produce these cells have been met with only modest success. In an attempt of finding new approaches, atmospheric-pressure room-temperature microplasma jets (MPJs) are shown to effectively direct in vitro differentiation of neural stem cells (NSCs) predominantly into neuronal lineage. Murine neural stem cells (C17.2-NSCs) treated with MPJs exhibit rapid proliferation and differentiation with longer neurites and cell bodies eventually forming neuronal networks. MPJs regulate ~75% of NSCs to differentiate into neurons, which is a higher efficiency compared to common protein- and growth factors-based differentiation. NSCs exposure to quantized and transient (~150 ns) micro-plasma bullets up-regulates expression of different cell lineage markers as β-Tubulin III (for neurons) and O4 (for oligodendrocytes), while the expression of GFAP (for astrocytes) remains unchanged, as evidenced by quantitative PCR, immunofluorescence microscopy and Western Blot assay. It is shown that the plasma-increased nitric oxide (NO) production is a factor in the fate choice and differentiation of NSCs followed by axonal growth. The differentiated NSC cells matured and produced mostly cholinergic and motor neuronal progeny. It is also demonstrated that exposure of primary rat NSCs to the microplasma leads to quite similar differentiation effects. This suggests that the observed effect may potentially be generic and applicable to other types of neural progenitor cells. The application of this new in vitro strategy to selectively differentiate NSCs into neurons represents a step towards reproducible and efficient production of the desired NSC derivatives. Published by Elsevier B.V.

Selective neuronal differentiation of neural stem cells induced by nanosecond microplasma agitation

Directory of Open Access Journals (Sweden)

Z. Xiong

2014-03-01

Full Text Available An essential step for therapeutic and research applications of stem cells is their ability to differentiate into specific cell types. Neuronal cells are of great interest for medical treatment of neurodegenerative diseases and traumatic injuries of central nervous system (CNS, but efforts to produce these cells have been met with only modest success. In an attempt of finding new approaches, atmospheric-pressure room-temperature microplasma jets (MPJs are shown to effectively direct in vitro differentiation of neural stem cells (NSCs predominantly into neuronal lineage. Murine neural stem cells (C17.2-NSCs treated with MPJs exhibit rapid proliferation and differentiation with longer neurites and cell bodies eventually forming neuronal networks. MPJs regulate ~75% of NSCs to differentiate into neurons, which is a higher efficiency compared to common protein- and growth factors-based differentiation. NSCs exposure to quantized and transient (~150 ns micro-plasma bullets up-regulates expression of different cell lineage markers as β-Tubulin III (for neurons and O4 (for oligodendrocytes, while the expression of GFAP (for astrocytes remains unchanged, as evidenced by quantitative PCR, immunofluorescence microscopy and Western Blot assay. It is shown that the plasma-increased nitric oxide (NO production is a factor in the fate choice and differentiation of NSCs followed by axonal growth. The differentiated NSC cells matured and produced mostly cholinergic and motor neuronal progeny. It is also demonstrated that exposure of primary rat NSCs to the microplasma leads to quite similar differentiation effects. This suggests that the observed effect may potentially be generic and applicable to other types of neural progenitor cells. The application of this new in vitro strategy to selectively differentiate NSCs into neurons represents a step towards reproducible and efficient production of the desired NSC derivatives.

DNA methylation differentially regulates cytokine secretion in gingival epithelia in response to bacterial challenges.

Science.gov (United States)

Drury, Jeanie L; Chung, Whasun Oh

2015-03-01

Epigenetic modifications are changes in gene expression without altering DNA sequence. We previously reported that bacteria-specific innate immune responses are regulated by epigenetic modifications. Our hypothesis is that DNA methylation affects gingival cytokine secretion in response to bacterial stimulation. Gingival epithelial cells (GECs) were treated with DNMT-1 inhibitors prior to Porphyromonas gingivalis (Pg) or Fusobacterium nucleatum (Fn) exposure. Protein secretion was assessed using ELISA. Gene expression was quantified using qRT-PCR. The ability of bacteria to invade inhibitor pretreated GECs was assessed utilizing flow cytometry. Changes were compared to unstimulated GECs. GEC upregulation of IL-6 and CXCL1 by Pg or Fn stimulation was significantly diminished by inhibitor pretreatment. Pg stimulated IL-1α secretion and inhibitor pretreatment significantly enhanced this upregulation, while Fn alone or with inhibitor pretreatment had no effect on IL-1α expression. GEC upregulation of human beta-definsin-2 in response to Pg and Fn exposure was enhanced following the inhibitor pretreatment. GEC susceptibility to bacterial invasion was unaltered. These results suggest that DNA methylation differentially affects gingival cytokine secretion in response to Pg or Fn. Our data provide basis for better understanding of how epigenetic modifications, brought on by exposure to oral bacteria, will subsequently affect host susceptibility to oral diseases. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Differential Effects of Sodium Butyrate and Lithium Chloride on Rhesus Monkey Trophoblast Differentiation.

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Priyadarsini Kumar

� production. The results provide valuable tools to manipulate trophoblast differentiation in vitro and to better understand the differentiation pathways that occur during early gestation.

Pseudo-differential operators groups, geometry and applications

CERN Document Server

Zhu, Hongmei

2017-01-01

This volume consists of papers inspired by the special session on pseudo-differential operators at the 10th ISAAC Congress held at the University of Macau, August 3-8, 2015 and the mini-symposium on pseudo-differential operators in industries and technologies at the 8th ICIAM held at the National Convention Center in Beijing, August 10-14, 2015. The twelve papers included present cutting-edge trends in pseudo-differential operators and applications from the perspectives of Lie groups (Chapters 1-2), geometry (Chapters 3-5) and applications (Chapters 6-12). Many contributions cover applications in probability, differential equations and time-frequency analysis. A focus on the synergies of pseudo-differential operators with applications, especially real-life applications, enhances understanding of the analysis and the usefulness of these operators.

Mixed chemical-induced oxidative stress in occupational exposure ...

African Journals Online (AJOL)

Mixed chemical-induced oxidative stress in occupational exposure in Nigerians. JI Anetor, SA Yaqub, GO Anetor, AC Nsonwu, FAA Adeniyi, S Fukushima. Abstract. Exposure to single chemicals and associated disorders in occupational environments has received significant attention. Understanding these events holds ...

The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice

Energy Technology Data Exchange (ETDEWEB)

Hao, Chan-Juan; Cheng, Xue-Jia; Xia, Hong-Fei, E-mail: hongfeixia@yahoo.com.cn; Ma, Xu

2012-08-15

Epidemiology studies indicate that exposure to endocrine disruptors during developmental “window” contributes to adipogenesis and the development of obesity. Implication of endocrine disruptor such as diethylstilbestrol (DES) on adipose tissue development has been poorly investigated. Here we evaluated the effects of DES on adipocyte differentiation in vitro and in vivo, and explored potential mechanism involved in its action. DES induced 3T3-L1 preadipocyte differentiation in a dose-dependent manner, and activated the expression of estrogen receptor (ER) and peroxisome proliferator-acivated receptor (PPAR) γ as well as its target genes required for adipogenesis in vitro. ER mediated the enhancement of DES-induced PPARγ activity. Moreover, DES perturbed key regulators of adipogenesis and lipogenic pathway in vivo. In utero exposure to low dose of DES significantly increased body weight, liver weight and fat mass in female offspring at postnatal day (PND) 60. In addition, serum triglyceride and glucose levels were also significantly elevated. These results suggest that perinatal exposure to DES may be expected to increase the incidence of obesity in a sex-dependent manner and can act as a potential chemical stressor for obesity and obesity-related disorders. -- Highlights: ► DES induced adipocyte differentiation in a dose-dependent manner in 3T3-L1 cells. ► DES activated adipogenic critical regulators and markers in vitro and in vivo. ► Perinatal exposure to DES led to the obese phenotype in female offspring. ► DES might be a potential chemical stressor for obesity and obesity-related disorders.

The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice

International Nuclear Information System (INIS)

Hao, Chan-Juan; Cheng, Xue-Jia; Xia, Hong-Fei; Ma, Xu

2012-01-01

Epidemiology studies indicate that exposure to endocrine disruptors during developmental “window” contributes to adipogenesis and the development of obesity. Implication of endocrine disruptor such as diethylstilbestrol (DES) on adipose tissue development has been poorly investigated. Here we evaluated the effects of DES on adipocyte differentiation in vitro and in vivo, and explored potential mechanism involved in its action. DES induced 3T3-L1 preadipocyte differentiation in a dose-dependent manner, and activated the expression of estrogen receptor (ER) and peroxisome proliferator-acivated receptor (PPAR) γ as well as its target genes required for adipogenesis in vitro. ER mediated the enhancement of DES-induced PPARγ activity. Moreover, DES perturbed key regulators of adipogenesis and lipogenic pathway in vivo. In utero exposure to low dose of DES significantly increased body weight, liver weight and fat mass in female offspring at postnatal day (PND) 60. In addition, serum triglyceride and glucose levels were also significantly elevated. These results suggest that perinatal exposure to DES may be expected to increase the incidence of obesity in a sex-dependent manner and can act as a potential chemical stressor for obesity and obesity-related disorders. -- Highlights: ► DES induced adipocyte differentiation in a dose-dependent manner in 3T3-L1 cells. ► DES activated adipogenic critical regulators and markers in vitro and in vivo. ► Perinatal exposure to DES led to the obese phenotype in female offspring. ► DES might be a potential chemical stressor for obesity and obesity-related disorders.

Dynamic data analysis modeling data with differential equations

CERN Document Server

Ramsay, James

2017-01-01

This text focuses on the use of smoothing methods for developing and estimating differential equations following recent developments in functional data analysis and building on techniques described in Ramsay and Silverman (2005) Functional Data Analysis. The central concept of a dynamical system as a buffer that translates sudden changes in input into smooth controlled output responses has led to applications of previously analyzed data, opening up entirely new opportunities for dynamical systems. The technical level has been kept low so that those with little or no exposure to differential equations as modeling objects can be brought into this data analysis landscape. There are already many texts on the mathematical properties of ordinary differential equations, or dynamic models, and there is a large literature distributed over many fields on models for real world processes consisting of differential equations. However, a researcher interested in fitting such a model to data, or a statistician interested in...

Excess Imidacloprid Exposure Causes the Heart Tube Malformation of Chick Embryos.

Science.gov (United States)

Gao, Lin-Rui; Li, Shuai; Zhang, Jing; Liang, Chang; Chen, En-Ni; Zhang, Shi-Yao; Chuai, Manli; Bao, Yong-Ping; Wang, Guang; Yang, Xuesong

2016-11-30

As a neonicotinoid pesticide, imidacloprid is widely used to control sucking insects on agricultural planting and fleas on domestic animals. However, the extent to which imidacloprid exposure has an influence on cardiogensis in early embryogenesis is still poorly understood. In vertebrates, the heart is the first organ to be formed. In this study, to address whether imidacloprid exposure affects early heart development, the early chick embryo has been used as an experimental model because of its accessibility at its early developmental stage. The results demonstrate that exposure of the early chick embryo to imidacloprid caused malformation of heart tube. Furthermore, the data reveal that down-regulation of GATA4, NKX2.5, and BMP4 and up-regulation of Wnt3a led to aberrant cardiomyocyte differentiation. In addition, imidacloprid exposure interfered with basement membrane breakdown, E-cadherin/laminin expression, and mesoderm formation during the epithelial-mesenchymal transition (EMT) in gastrula chick embryos. Finally, the DiI-labeled cell migration trajectory indicated that imidacloprid restricted the cell migration of cardiac progenitors to primary heart field in gastrula chick embryos. A similar observation was also obtained from the cell migration assay of scratch wounds in vitro. Additionally, imidacloprid exposure negatively affected the cytoskeleton structure and expression of corresponding adhesion molecules. Taken together, these results reveal that the improper EMT, cardiac progenitor migration, and differentiation are responsible for imidacloprid exposure-induced malformation of heart tube during chick embryo development.

Effects of Methylmercury exposure in 3T3-L1 Adipocytes

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Theresa Vertigan

2017-02-01

Full Text Available Mercury-containing compounds are environmental pollutants that have become increasingly consequential in the Arctic regions of North America due to processes of climate change increasing their release and availability at northern latitudes. Currently, the form of mercury known to be most detrimental to human health is methylmercury, CH3Hg+, which is found in the environment and accumulates in the tissues of piscivores, including those consumed by Alaska Natives through subsistence gathering. Much is known about the neurotoxicity of methylmercury after exposure to high concentrations, but little is known about toxicity to other tissues and cell types, particularly for long-term exposure and the lower concentrations that would occur through fish consumption. Effects of methylmercury exposure on 3T3-L1 adipocytes in culture were assessed using assays for cytotoxicity and an ELISA assay for vascular endothelial growth factor (VEGF, a signaling molecule shown to be important for maintaining metabolic status in adipose tissue. Results showed that exposure to methylmercury leads to significant toxicity in adipocytes at exposures of 100 ng/mL during later stages of differentiation, but lower methylmercury concentrations produced little to no toxicity. Results also showed that VEGF secretion is elevated in adipocytes exposed to methylmercury after the process of differentiating into mature, fat-storing cells. These results provide a basis for further exploration into metabolic consequences of methylmercury exposure on specific cell types and cell models.

Understanding pathways of exposure using site-specific habits surveys, particularly new pathways and methodologies

International Nuclear Information System (INIS)

Grzechnik, M.; McTaggart, K.; Clyne, F.

2006-01-01

Full text of publication follows: UK policy on the control of radiation exposure via routine discharges from nuclear licensed sites has long been based on ICRP recommendations that embody the principles of justification of practices, optimisation of protection, and dose limitation. Radiological protection of the public is based on the concept of a critical group of individuals. This group is defined as those people who, as a result of the area they reside and their habits, receive the highest radiation dose due to the operations of a site. Therefore, if the dose to this critical group is acceptable in relation to relevant dose limits and constraints, then other members of the public will receive lower doses. Thus, the principle of critical groups provides overall protection for the public. Surveys to determine local habits involve an integrated methodology, whereby the potential radioactive exposure pathways from liquid and gaseous discharges and direct radiation from the site are investigated. Surveys to identify these habits must be undertaken rigorously for consistency, and have been known to reveal unexpected pathways of radiation exposure. Pathways typically include consumption of local foodstuffs and external exposure. Furthermore, a number of critical groups ma y be identified within a single survey area if the habits of one group do not adequately describe those of the other inhabitants of the area. Survey preparation involves the initial identification of high producers and consumers of local foods in a geographically defined area surrounding the nuclear facility. Pathways can be broken down into three general groups, which include exposure arising from; 1) Terrestrial (gaseous) discharges surveyed within 5 km of the site 2) Direct radiation surveyed within 1 km of the site 3) Aquatic (liquid) discharges surveyed within local areas affected by the discharges, including seas, rivers and sewage works. The survey fieldwork involves interviewing members of the

Influence of high- and low-LET radiation on the cardiac differentiation of mouse embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Helm, Alexander

2013-07-19

The in utero exposure to ionising radiation poses a risk for the radiosensitive developing embryo. Effects of low-LET radiation on different developmental stages of the embryo are relatively well known due to experimental studies and epidemiological data. Data for effects on the very early stage of the embryonic development, particularly the effects of high-LET radiation instead are rather limited. However, unanticipated exposures of the early embryo to ionising radiation may occur through diagnostic or therapeutic applications or through radiation accidents. Additionally, protons and carbon ions are increasingly used in radiotherapy. Thus, a risk estimation of high-LET exposure especially to the early embryo is of a certain importance. To address this topic, pluripotent mouse embryonic stem cells resembling the blastocyst stage were irradiated with high-LET carbon ions or low-LET X-rays and subsequently differentiated to mimic the early embryonic development. The occurrence of spontaneously contracting cardiomyocytes was used as a marker to asses the radiation effects on the differentiation. Among others, cell inactivation, cell death and gene expression were analysed. A delay in the cardiac differentiation after radiation exposure was found. The results point to radiation-induced cell killing as the main effector of the developmental delay. Carbon ions were found to be more effective than X-rays.

A microscopic derivation of stochastic differential equations

International Nuclear Information System (INIS)

Arimitsu, Toshihico

1996-01-01

With the help of the formulation of Non-Equilibrium Thermo Field Dynamics, a unified canonical operator formalism is constructed for the quantum stochastic differential equations. In the course of its construction, it is found that there are at least two formulations, i.e. one is non-hermitian and the other is hermitian. Having settled which framework should be satisfied by the quantum stochastic differential equations, a microscopic derivation is performed for these stochastic differential equations by extending the projector methods. This investigation may open a new field for quantum systems in order to understand the deeper meaning of dissipation

Age of Bilingual Exposure Is Related to the Contribution of Phonological and Semantic Knowledge to Successful Reading Development.

Science.gov (United States)

Jasińska, Kaja K; Petitto, Laura-Ann

2018-01-01

Bilingual children's reading as a function of age of first bilingual language exposure (AoE) was examined. Bilingual (varied AoE) and monolingual children (N = 421) were compared in their English language and reading abilities (6-10 years) using phonological awareness, semantic knowledge, and reading tasks. Structural equation modeling was applied to determine how bilingual AoE predicts reading outcomes. Early exposed bilinguals outperformed monolinguals on phonological awareness and word reading. Phonology and semantic (vocabulary) knowledge differentially predicted reading depending on the bilingual experience and AoE. Understanding how bilingual experiences impact phonological awareness and semantic knowledge, and in turn, impact reading outcomes is relevant for our understanding of what language and reading skills are best to focus on, and when, to promote optimal reading success. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Undergraduate Students' Mental Operations in Systems of Differential Equations

Science.gov (United States)

Whitehead, Karen; Rasmussen, Chris

2003-01-01

This paper reports on research conducted to understand undergraduate students' ways of reasoning about systems of differential equations (SDEs). As part of a semester long classroom teaching experiment in a first course in differential equations, we conducted task-based interviews with six students after their study of first order differential…

Birth Order, Club Membership and Mass Media Exposure

Science.gov (United States)

Tomeh, Aida K.

1976-01-01

Examines the relationship between birth order, club membership and mass media exposure for women college students in Lebanon. Findings show the total membership rate and mass media consumption are higher among last born girls than first born. Birth order differences are explained in terms of the differential socialization of children. (Author)

Neonatal exposure to a glyphosate based herbicide alters the development of the rat uterus

International Nuclear Information System (INIS)

Guerrero Schimpf, Marlise; Milesi, María M.; Ingaramo, Paola I.; Luque, Enrique H.; Varayoud, Jorgelina

2017-01-01

Highlights: • Neonatal exposure to GBH lead to endometrial hyperplasia and increase proliferation. • GBH disrupts proteins involved in uterine organogenetic differentiation. • GBH exposure induced persistent increase of PR and Hoxa10 proteins. - Abstract: Glyphosate-based herbicides (GBHs) are extensively used to control weeds on both cropland and non-cropland areas. No reports are available regarding the effects of GBHs exposure on uterine development. We evaluated if neonatal exposure to a GBH affects uterine morphology, proliferation and expression of proteins that regulate uterine organogenetic differentiation in rats. Female Wistar pups received saline solution (control, C) or a commercial formulation of glyphosate (GBH, 2 mg/kg) by sc injection every 48 h from postnatal day (PND) 1 to PND7. Rats were sacrificed on PND8 (neonatal period) and PND21 (prepubertal period) to evaluate acute and short-term effects, respectively. The uterine morphology was evaluated in hematoxylin and eosin stained sections. The epithelial and stromal immunophenotypes were established by assessing the expression of luminal epithelial protein (cytokeratin 8; CK8), basal epithelial proteins (p63 and pan cytokeratin CK1, 5, 10 and 14); and vimentin by immunohistochemistry (IHC). To investigate changes on proteins that regulate uterine organogenetic differentiation we evaluated the expression of estrogen receptor alpha (ERα), progesterone receptor (PR), Hoxa10 and Wnt7a by IHC. The GBH-exposed uteri showed morphological changes, characterized by an increase in the incidence of luminal epithelial hyperplasia (LEH) and an increase in the stromal and myometrial thickness. The epithelial cells showed a positive immunostaining for CK8, while the stromal cells for vimentin. GBH treatment increased cell proliferation in the luminal and stromal compartment on PND8, without changes on PND21. GBH treatment also altered the expression of proteins involved in uterine organogenetic

Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure

International Nuclear Information System (INIS)

Sokolov, Mykyta V.; Panyutin, Irina V.; Panyutin, Igor G.; Neumann, Ronald D.

2011-01-01

One of the key consequences of exposure of human cells to genotoxic agents is the activation of DNA damage responses (DDR). While the mechanisms underpinning DDR in fully differentiated somatic human cells have been studied extensively, molecular signaling events and pathways involved in DDR in pluripotent human embryonic stem cells (hESC) remain largely unexplored. We studied changes in the human genome-wide transcriptome of H9 hESC line following exposures to 1 Gy of gamma-radiation at 2 h and 16 h post-irradiation. Quantitative real-time PCR was performed to verify the expression data for a subset of genes. In parallel, the cell growth, DDR kinetics, and expression of pluripotency markers in irradiated hESC were monitored. The changes in gene expression in hESC after exposure to ionizing radiation (IR) are substantially different from those observed in somatic human cell lines. Gene expression patterns at 2 h post-IR showed almost an exclusively p53-dependent, predominantly pro-apoptotic, signature with a total of only 30 up-regulated genes. In contrast, the gene expression patterns at 16 h post-IR showed 354 differentially expressed genes, mostly involved in pro-survival pathways, such as increased expression of metallothioneins, ubiquitin cycle, and general metabolism signaling. Cell growth data paralleled trends in gene expression changes. DDR in hESC followed the kinetics reported for human somatic differentiated cells. The expression of pluripotency markers characteristic of undifferentiated hESC was not affected by exposure to IR during the time course of our analysis. Our data on dynamics of transcriptome response of irradiated hESCs may provide a valuable tool to screen for markers of IR exposure of human cells in their most naive state; thus unmasking the key elements of DDR; at the same time, avoiding the complexity of interpreting distinct cell type-dependent genotoxic stress responses of terminally differentiated cells.

Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure

Energy Technology Data Exchange (ETDEWEB)

Sokolov, Mykyta V., E-mail: sokolovm@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Irina V., E-mail: ipanyutinv@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Igor G., E-mail: igorp@helix.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Neumann, Ronald D., E-mail: rneumann@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States)

2011-05-10

One of the key consequences of exposure of human cells to genotoxic agents is the activation of DNA damage responses (DDR). While the mechanisms underpinning DDR in fully differentiated somatic human cells have been studied extensively, molecular signaling events and pathways involved in DDR in pluripotent human embryonic stem cells (hESC) remain largely unexplored. We studied changes in the human genome-wide transcriptome of H9 hESC line following exposures to 1 Gy of gamma-radiation at 2 h and 16 h post-irradiation. Quantitative real-time PCR was performed to verify the expression data for a subset of genes. In parallel, the cell growth, DDR kinetics, and expression of pluripotency markers in irradiated hESC were monitored. The changes in gene expression in hESC after exposure to ionizing radiation (IR) are substantially different from those observed in somatic human cell lines. Gene expression patterns at 2 h post-IR showed almost an exclusively p53-dependent, predominantly pro-apoptotic, signature with a total of only 30 up-regulated genes. In contrast, the gene expression patterns at 16 h post-IR showed 354 differentially expressed genes, mostly involved in pro-survival pathways, such as increased expression of metallothioneins, ubiquitin cycle, and general metabolism signaling. Cell growth data paralleled trends in gene expression changes. DDR in hESC followed the kinetics reported for human somatic differentiated cells. The expression of pluripotency markers characteristic of undifferentiated hESC was not affected by exposure to IR during the time course of our analysis. Our data on dynamics of transcriptome response of irradiated hESCs may provide a valuable tool to screen for markers of IR exposure of human cells in their most naive state; thus unmasking the key elements of DDR; at the same time, avoiding the complexity of interpreting distinct cell type-dependent genotoxic stress responses of terminally differentiated cells.

Synergistic effects of tributyltin and 2,3,7,8-tetrachlorodibenzo-p-dioxin on differentiating osteoblasts and osteoclasts

International Nuclear Information System (INIS)

Koskela, Antti; Viluksela, Matti; Keinänen, Meeri; Tuukkanen, Juha; Korkalainen, Merja

2012-01-01

The purpose of this study was to examine the effects of the persistent and accumulative environmental pollutants tributyltin (TBT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) individually and in combination on differentiating bone cells. TBT and TCDD are chemically distinct compounds with different mechanisms of toxicity, but they typically have the same sources of exposure and both have been shown to affect bone development at low exposure levels. Bone marrow stem cells were isolated from femurs and tibias of C57BL/6 J mice, differentiated in culture into osteoblasts or osteoclasts and exposed to 0.1–10 nM TBT, 0.01–1 nM TCDD or 10 nM TBT + 1 nM TCDD. In osteoblasts, the combined exposure to TBT and TCDD significantly decreased the mRNA expression of alkaline phosphatase and osteocalcin more than TBT or TCDD alone. PCR array showed different gene expression profiles for TBT and TCDD individually, and the combination evoked several additional alterations in gene expression. Expression of aryl hydrocarbon receptor repressor (AHRR) was increased by TCDD as expected, but simultaneous exposure to TBT prevented the increase thus potentially strengthening AHR-mediated effects of TCDD. The number of osteoclasts was reduced by TCDD alone and in combination with TBT, but TBT alone had no effect. However, the total area of resorbed bone was remarkably lower after combined exposure than after TBT or TCDD alone. In conclusion, very low concentrations of TBT and TCDD have synergistic deleterious effects on bone formation and additive effects on bone resorption. -- Highlights: ► Combined exposure to TCDD and TBT evoked a unique gene expression profile. ► Osteoblast differentiation was synergistically disturbed after combined exposure. ► Bone resorbing activity was additively decreased after combined exposure.

Synergistic effects of tributyltin and 2,3,7,8-tetrachlorodibenzo-p-dioxin on differentiating osteoblasts and osteoclasts

Energy Technology Data Exchange (ETDEWEB)

Koskela, Antti, E-mail: antti.koskela@oulu.fi [University of Oulu, Department of Anatomy and Cell Biology, Oulu (Finland); Viluksela, Matti [National Institute for Health and Welfare, Department of Environmental Health, Kuopio (Finland); Keinänen, Meeri; Tuukkanen, Juha [University of Oulu, Department of Anatomy and Cell Biology, Oulu (Finland); Korkalainen, Merja [National Institute for Health and Welfare, Department of Environmental Health, Kuopio (Finland)

2012-09-01

The purpose of this study was to examine the effects of the persistent and accumulative environmental pollutants tributyltin (TBT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) individually and in combination on differentiating bone cells. TBT and TCDD are chemically distinct compounds with different mechanisms of toxicity, but they typically have the same sources of exposure and both have been shown to affect bone development at low exposure levels. Bone marrow stem cells were isolated from femurs and tibias of C57BL/6 J mice, differentiated in culture into osteoblasts or osteoclasts and exposed to 0.1–10 nM TBT, 0.01–1 nM TCDD or 10 nM TBT + 1 nM TCDD. In osteoblasts, the combined exposure to TBT and TCDD significantly decreased the mRNA expression of alkaline phosphatase and osteocalcin more than TBT or TCDD alone. PCR array showed different gene expression profiles for TBT and TCDD individually, and the combination evoked several additional alterations in gene expression. Expression of aryl hydrocarbon receptor repressor (AHRR) was increased by TCDD as expected, but simultaneous exposure to TBT prevented the increase thus potentially strengthening AHR-mediated effects of TCDD. The number of osteoclasts was reduced by TCDD alone and in combination with TBT, but TBT alone had no effect. However, the total area of resorbed bone was remarkably lower after combined exposure than after TBT or TCDD alone. In conclusion, very low concentrations of TBT and TCDD have synergistic deleterious effects on bone formation and additive effects on bone resorption. -- Highlights: ► Combined exposure to TCDD and TBT evoked a unique gene expression profile. ► Osteoblast differentiation was synergistically disturbed after combined exposure. ► Bone resorbing activity was additively decreased after combined exposure.

Gendered depression: Vulnerability or exposure to work and family stressors?

Science.gov (United States)

Marchand, Alain; Bilodeau, Jaunathan; Demers, Andrée; Beauregard, Nancy; Durand, Pierre; Haines, Victor Y

2016-10-01

Research has shown that employed women are more prone to depression than men, but the pathways linking gender to depression remain poorly understood. The aim of this study was to examine how work and family conditions operated as potentially gendered antecedents of depression. It evaluated more specifically how differences in depressive symptoms in women and men could be explained by their differential vulnerability and exposure to work and family conditions, as well as by the mediating role of work-to-family conflict (WFC) and family-to-work conflict (FWC). Data were collected in 2009-2012 from a sample of 1935 employees (48.9% women) nested in 63 workplaces in the province of Quebec (Canada). Data were analyzed with multilevel path analysis models to test for the differential exposure hypothesis, and stratified by gender to test for the differential vulnerability hypothesis. Results supported both hypothesizes, but only WFC played a mediating role between work-family stressors and depression. Regarding the vulnerability hypothesis, WFC was more strongly associated with women depressive symptoms, and the magnitude of the association between family income and WFC was stronger for women. Overall, the differential exposure hypothesis seemed to reach a greater empirical support. After accounting for work and family stressors as well as WFC, differences in depressive symptoms in women and men were no longer significantly, as WFC, working hours, irregular work schedule and skill utilization acted as mediators. WFC associated with higher depressive symptoms and skill utilization with lower depressive symptoms. WFC related to higher working hours and irregular work schedule. Compared to men, women reported higher WFC, but lower working hours, less irregular work schedule and lower skill utilization at work. Women's higher rate of depression is intrinsically linked to their different social experiences as shaped by a gendered social structure and gendered organizations

Source apportionment of air pollution exposures of rural Chinese women cooking with biomass fuels

Science.gov (United States)

Huang, Wei; Baumgartner, Jill; Zhang, Yuanxun; Wang, Yuqin; Schauer, James J.

2015-03-01

Particulate matter (PM) from different sources may differentially affect human health. Few studies have assessed the main sources of personal exposure to PM and their contributions among residents of developing countries, where pollution sources differ from those in higher-income settings. 116 daily (24-h) personal PM2.5 exposure samples were collected among 81 women cooking with biomass fuels in two villages in rural Yunnan, China. The PM samples were analyzed for mass and chemical composition, including water-soluble organic carbon (WSOC), black carbon (BC), and molecular markers. We found black carbon, n-alkanes and levoglucosan dominated the most abundant fractions of the total measured species and average personal PM2.5 exposure was higher in winter than that in summer in both villages. The composition data were then analyzed using a positive matrix factorization (PMF) receptor model to identify the main PM emission sources contributing to women's exposures and to assess their spatial (between villages) and seasonal variation in our study setting. The 6-factor solution provided reasonably stable profiles and was selected for further analysis. Our results show that rural Chinese women cooking with biomass fuels are exposed to a variety of sources. The identified factors include wood combustion (41.1%), a cooking source (35.6%), a mobile source (12.6%), plant waxes (6.7%), pyrolysis combustion (3.0%), and secondary organic aerosols (SOA; 1.0%). The mean source contributions of the mobile source, cooking source, and wood combustion factor to PM2.5 exposure were significantly different between women living in the two study villages, whereas the mean SOA, wood combustion, and plant waxes factors differed seasonally. There was no relationship between source contributions and questionnaire-based measurements of source-specific exposures, implying that the impacts of source contributions on exposure are affected by complex spatial, temporal and behavioral patterns

The inverse hazard law: blood pressure, sexual harassment, racial discrimination, workplace abuse and occupational exposures in US low-income black, white and Latino workers.

Science.gov (United States)

Krieger, Nancy; Chen, Jarvis T; Waterman, Pamela D; Hartman, Cathy; Stoddard, Anne M; Quinn, Margaret M; Sorensen, Glorian; Barbeau, Elizabeth M

2008-12-01

Research on societal determinants of health suggests the existence of an "inverse hazard law," which we define as: "The accumulation of health hazards tends to vary inversely with the power and resources of the populations affected." Yet, little empirical research has systematically investigated this topic, including in relation to workplace exposures. We accordingly designed the United for Health study (Greater Boston Area, Massachusetts, 2003-2004) to investigate the joint distribution and health implications of workplace occupational hazards (dust, fumes, chemical, noise, ergonomic strain) and social hazards (racial discrimination, sexual harassment, workplace abuse). Focusing on blood pressure as our health outcome, we found that among the 1202 low-income multi-racial/ethnic working class participants in our cohort - of whom 40% lived below the US poverty line - 79% reported exposure to at least one social hazard and 82% to at least one high-exposure occupational hazard. Only sexual harassment, the least common social hazard, was associated with elevated systolic blood pressure (SBP) among the women workers. By contrast, no statistically significant associations were detectable between the other additional highly prevalent social and occupational hazards and SBP; we did, however, find suggestive evidence of an association between SBP and response to unfair treatment, implying that in a context of high exposure, differential susceptibility to the exposure matters. These results interestingly contrast to our prior findings for this same cohort, in which we found associations between self-reported experiences of racial discrimination and two other health outcomes: psychological distress and cigarette smoking. Likely explanations for these contrasting findings include: (a) the differential etiologic periods and pathways involving somatic health, mental health, and health behaviors, and (b) the high prevalence of adverse exposures, limiting the ability to detect

Defining and Differentiating the Makerspace

Science.gov (United States)

Dousay, Tonia A.

2017-01-01

Many resources now punctuate the maker movement landscape. However, some schools and communities still struggle to understand this burgeoning movement. How do we define these spaces and differentiate them from previous labs and shops? Through a multidimensional framework, stakeholders should consider how the structure, access, staffing, and tools…

[Sex differentiation of central nervous system--brain of man and woman].

Science.gov (United States)

Arai, Yasumasa

2004-02-01

Sex differentiation of human brain is mostly dependent on the prenatal exposure to androgen(testosterone). Congenital aromatase deficiency does not disturb male brain development in men. This is quite different from experimental evidence from rodents whose brains need intraneuronal aromatization from androgen to estrogen to induce sex differentiation. There is evidence for male-female differences in brain structures. Some of them(INHA-3) appear to be related with sexual orientation. The other(BNST) might participate in forming gender-identity. In addition, sexually dimorphic features are recognized in some cognitive activities. The possible involvement of genetic factors in human brain sex differentiation is also discussed.

The emerging causal understanding of institutional objects.

Science.gov (United States)

Noyes, Alexander; Keil, Frank C; Dunham, Yarrow

2018-01-01

Institutional objects, such as money, drivers' licenses, and borders, have functions because of their social roles rather than their immediate physical properties. These objects are causally different than standard artifacts (e.g. hammers, chairs, and cars), sharing more commonality with other social roles. Thus, they inform psychological theories of human-made objects as well as children's emerging understanding of social reality. We examined whether children (N=180, ages 4-9) differentiate institutional objects from standard artifacts. Specifically, we examine whether children understand that mutual intentions (i.e., the intentions of a social collective) underlie the functional affordances of institutional objects in ways that they do not for standard artifacts. We find that young children assimilate institutional objects into their intuitive theories of standard artifacts; children begin to differentiate between the domains in the elementary school years. Published by Elsevier B.V.

Time and frequency weightings and the assessment of sound exposure

DEFF Research Database (Denmark)

Ordoñez, Rodrigo Pizarro; de Toro, Miguel Angel Aranda; Hammershøi, Dorte

2010-01-01

Since the development of averaging/integrating sound level meters and frequency weighting networks in the 1950’s, measurement of the physical characteristics of sound has not changed a great deal. Advances have occurred in how the measured values are used (day-night averages, limit and action...... of the exposure. This information is being used to investigate metrics that can differentiate temporal characteristics (impulsive, fluctuating) as well as frequency characteristics (narrow-band or tonal dominance) of sound exposures. This presentation gives an overview of the existing sound measurement...... and analysis methods, that can provide a better representation of the effects of sound exposures on the hearing system...

Transcriptomics-based identification of developmental toxicants through their interference with cardiomyocyte differentiation of embryonic stem cells

International Nuclear Information System (INIS)

Dartel, Dorien A.M. van; Pennings, Jeroen L.A.; Schooten, Frederik J. van; Piersma, Aldert H.

2010-01-01

The embryonic stem cell test (EST) predicts developmental toxicity based on the inhibition of cardiomyocyte differentiation of embryonic stem cells (ESC). The subjective endpoint, the long culture duration together with the undefined applicability domain and related predictivity need further improvement to facilitate implementation of the EST into regulatory strategies. These aspects may be improved by studying gene expression changes in the ESC differentiation cultures and their modulation by compound exposure using transcriptomics. Here, we tested the developmental toxicants monobutyl phthalate and 6-aminonicotinamide. ESC were allowed to differentiated, and cardiomyocyte differentiation was assessed after 10 days of culture. RNA of solvent controls was collected after 0, 24, 48, 72 and 96 h of exposure, and RNA of developmental-toxicant-exposed cultures was collected after 24 and 96 h. Samples were hybridized to DNA microarrays, and 1355 genes were found differentially expressed among the unexposed experimental groups. These regulated genes were involved in differentiation-related processes, and Principal Component Analysis (PCA) based on these genes showed that the unexposed experimental groups appeared in chronological order in the PCA, which can therefore be regarded as a continuous representation of the differentiation track. The developmental-toxicant-exposed cultures appeared to deviate significantly from this differentiation track, which confirms the compound-modulating effects on the differentiation process. The incorporation of transcriptomics in the EST is expected to provide a more informative and improved endpoint in the EST as compared with morphology, allowing early detection of differentiation modulation. Furthermore, this approach may improve the definition of the applicability domain and predictivity of the EST.

A dermatotoxicokinetic model of human exposures to jet fuel.

Science.gov (United States)

Kim, David; Andersen, Melvin E; Nylander-French, Leena A

2006-09-01

Workers, both in the military and the commercial airline industry, are exposed to jet fuel by inhalation and dermal contact. We present a dermatotoxicokinetic (DTK) model that quantifies the absorption, distribution, and elimination of aromatic and aliphatic components of jet fuel following dermal exposures in humans. Kinetic data were obtained from 10 healthy volunteers following a single dose of JP-8 to the forearm over a surface area of 20 cm2. Blood samples were taken before exposure (t = 0 h), after exposure (t = 0.5 h), and every 0.5 h for up to 3.5 h postexposure. The DTK model that best fit the data included five compartments: (1) surface, (2) stratum corneum (SC), (3) viable epidermis, (4) blood, and (5) storage. The DTK model was used to predict blood concentrations of the components of JP-8 based on dermal-exposure measurements made in occupational-exposure settings in order to better understand the toxicokinetic behavior of these compounds. Monte Carlo simulations of dermal exposure and cumulative internal dose demonstrated no overlap among the low-, medium-, and high-exposure groups. The DTK model provides a quantitative understanding of the relationship between the mass of JP-8 components in the SC and the concentrations of each component in the systemic circulation. The model may be used for the development of a toxicokinetic modeling strategy for multiroute exposure to jet fuel.

Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk

Energy Technology Data Exchange (ETDEWEB)

Labib, Sarah, E-mail: Sarah.Labib@hc-sc.gc.ca; Guo, Charles H., E-mail: Charles.Guo@hc-sc.gc.ca; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca; Yauk, Carole L., E-mail: Carole.Yauk@hc-sc.gc.ca; White, Paul A., E-mail: Paul.White@hc-sc.gc.ca; Halappanavar, Sabina, E-mail: Sabina.Halappanavar@hc-sc.gc.ca

2013-12-01

Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mg BaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans. - Highlights: • Benzo(a)pyrene-mediated transcriptomic response in the forestomach was examined. • The immunoproteosome subunits and MHC class I

The effect of UV exposure and heat treatment on crystallization behavior of photosensitive glasses

Science.gov (United States)

Kıbrıslı, Orhan; Ersundu, Ali Erçin

2018-05-01

In this study, photosensitive glasses in the Na2O-ZnO-Al2O3-SiO2 system with photosensitizing agents (cerium, silver, tin, antimony) and halogenides (NaF and KBr) were synthesized through a conventional melt-quenching technique. The crystallization mechanism was investigated for solely heat-treated and UV-exposed + heat-treated samples using differential thermal analysis (DTA), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM) techniques to understand the effect of UV exposure on crystallization behavior of photosensitive glasses. Accordingly, non-isothermal DTA measurements were performed at different heating rates to determine crystallization peak, T p, and onset, T c, temperatures. For solely heat-treated samples, the kinetic parameters such as the Avrami constant, n, and morphology index, m, were calculated as 1 from the Ozawa method indicating surface crystallization and the value of crystallization activation energy was calculated as 944 kJ/mol using modified Kissinger method. On the contrary, bulk crystallization was found to be predominant for UV exposed + heat-treated samples revealing that UV exposure is the primary cause of bulk crystallization in photosensitive glasses.

Beyond Extinction: Prolonged Conditioning and Repeated Threat Exposure Abolish Contextual Renewal of Fear-Potentiated Startle Discrimination but Leave Expectancy Ratings Intact.

Science.gov (United States)

Leer, Arne; Haesen, Kim; Vervliet, Bram

2018-01-01

Extinction treatments decrease fear via repeated exposures to the conditioned stimulus (CS) and are associated with a return of fear. Alternatively, fear can be reduced via reductions in the perceived intensity of the unconditioned stimulus (US), e.g., through repeated exposures to the US. Promisingly, the few available studies show that repeated US exposures outperform standard extinction. US exposure treatments can decrease fear via two routes: (1) by weakening the CS-US association (extinction-like mechanism), and/or (2) by weakening the subjective US aversiveness (habituation-like mechanism). The current study further investigated the conditions under which US exposure treatment may reduce renewal, by adding a group in which CS-US pairings continued following fear acquisition. During acquisition, participants learned that one of two visual stimuli (CS+/CS-) predicted the occurrence of an aversive electrocutaneous stimulus (US). Next, the background context changed and participants received one of three interventions: repeated CS exposures, (2) repeated US exposures, or (3) continued CS-US pairings. Following repeated CS exposures, test presentations of the CSs in the original conditioning context revealed intact CS+/CS- differentiation in the fear-potentiated startle reflex, while the differentiation was abolished in the other two groups. Differential US expectancy ratings, on the other hand, were intact in all groups. Skin conductance data were inconclusive because standard context renewal following CS exposures did not occur. Unexpectedly, there was no evidence for a habituation-like process having taken place during US exposures or continued CS-US pairings. The results provide further evidence that US exposures outperform the standard extinction treatment and show that effects are similar when US exposures are part of CS-US pairings.

Clustering of Sun Exposure Measurements

DEFF Research Database (Denmark)

Have, Anna Szynkowiak; Larsen, Jan; Hansen, Lars Kai

2002-01-01

In a medically motivated Sun-exposure study, questionnaires concerning Sun-habits were collected from a number of subjects together with UV radiation measurements. This paper focuses on identifying clusters in the heterogeneous set of data for the purpose of understanding possible relations between...... Sun-habits exposure and eventually assessing the risk of skin cancer. A general probabilistic framework originally developed for text and Web mining is demonstrated to be useful for clustering of behavioral data. The framework combines principal component subspace projection with probabilistic...

Molecular initiating events of the intersex phenotype: Low-dose exposure to 17α-ethinylestradiol rapidly regulates molecular networks associated with gonad differentiation in the adult fathead minnow testis

International Nuclear Information System (INIS)

Feswick, April; Loughery, Jennifer R.; Isaacs, Meghan A.; Munkittrick, Kelly R.; Martyniuk, Christopher J.

2016-01-01

Highlights: • Male fathead minnow were exposed to 17alpha ethinylestradiol (EE2). • Both 11-ketotestosterone and testosterone production was decreased relative to controls. • A gene network associated with doublesex and mab-3 related transcription factor 1 were suppressed. • Genes involved in granulosa cell development were increased and sensitive to EE2 exposure. • Molecular initiating events that may be related to the intersex condition were identified. - Abstract: Intersex, or the presence of oocytes in the testes, has been documented in fish following exposure to wastewater effluent and estrogenic compounds. However, the molecular networks underlying the intersex condition are not completely known. To address this, we exposed male fathead minnows to a low, environmentally-relevant concentration of 17alpha-ethinylestradiol (EE2) (15 ng/L) and measured the transcriptome response in the testis after 96 h to identify early molecular initiating events that may proceed the intersex condition. The short-term exposure to EE2 did not affect gonadosomatic index and proportion of gametes within the testes. However, the production of 11-ketotestosterone and testosterone from the testis in vitro was decreased relative to controls. Expression profiling using a 8 × 60 K fathead minnow microarray identified 10 transcripts that were differentially expressed in the testes, the most dramatic change being that of coagulation factor XIII A chain (20-fold increase). Transcripts that included guanine nucleotide binding protein (Beta Polypeptide 2), peroxisome proliferator-activated receptor delta, and WNK lysine deficient protein kinase 1a, were down-regulated by EE2. Subnetwork enrichment analysis revealed that EE2 suppressed transcriptional networks associated with steroid metabolism, hormone biosynthesis, and sperm mobility. Most interesting was that gene networks associated with doublesex and mab-3 related transcription factor 1 (dmrt1) were suppressed in the adult

Molecular initiating events of the intersex phenotype: Low-dose exposure to 17α-ethinylestradiol rapidly regulates molecular networks associated with gonad differentiation in the adult fathead minnow testis

Energy Technology Data Exchange (ETDEWEB)

Feswick, April; Loughery, Jennifer R.; Isaacs, Meghan A.; Munkittrick, Kelly R.; Martyniuk, Christopher J., E-mail: cmartyni@yahoo.ca

2016-12-15

Highlights: • Male fathead minnow were exposed to 17alpha ethinylestradiol (EE2). • Both 11-ketotestosterone and testosterone production was decreased relative to controls. • A gene network associated with doublesex and mab-3 related transcription factor 1 were suppressed. • Genes involved in granulosa cell development were increased and sensitive to EE2 exposure. • Molecular initiating events that may be related to the intersex condition were identified. - Abstract: Intersex, or the presence of oocytes in the testes, has been documented in fish following exposure to wastewater effluent and estrogenic compounds. However, the molecular networks underlying the intersex condition are not completely known. To address this, we exposed male fathead minnows to a low, environmentally-relevant concentration of 17alpha-ethinylestradiol (EE2) (15 ng/L) and measured the transcriptome response in the testis after 96 h to identify early molecular initiating events that may proceed the intersex condition. The short-term exposure to EE2 did not affect gonadosomatic index and proportion of gametes within the testes. However, the production of 11-ketotestosterone and testosterone from the testis in vitro was decreased relative to controls. Expression profiling using a 8 × 60 K fathead minnow microarray identified 10 transcripts that were differentially expressed in the testes, the most dramatic change being that of coagulation factor XIII A chain (20-fold increase). Transcripts that included guanine nucleotide binding protein (Beta Polypeptide 2), peroxisome proliferator-activated receptor delta, and WNK lysine deficient protein kinase 1a, were down-regulated by EE2. Subnetwork enrichment analysis revealed that EE2 suppressed transcriptional networks associated with steroid metabolism, hormone biosynthesis, and sperm mobility. Most interesting was that gene networks associated with doublesex and mab-3 related transcription factor 1 (dmrt1) were suppressed in the adult

Perinatal Exposure to Low Levels of the Environmental Antiandrogen Vinclozolin Alters Sex-Differentiated Social Play and Sexual Behaviors in the Rat

Science.gov (United States)

Colbert, Nathan K.W.; Pelletier, Nicole C.; Cote, Joyce M.; Concannon, John B.; Jurdak, Nicole A.; Minott, Sara B.; Markowski, Vincent P.

2005-01-01

In this study we examined the effects of exposure to the antiandrogenic fungicide vinclozolin (Vz) on the development of two sex-differentiated behaviors that are organized by the perinatal actions of androgens. Pregnant Long-Evans rats were administered a daily oral dose of 0, 1.5, 3, 6, or 12 mg/kg Vz from the 14th day of gestation through postnatal day (PND)3. The social play behavior of juvenile offspring was examined on PND22 and again on PND34 during play sessions with a same-sex littermate. After they reached adulthood, the male offspring were examined with the ex copula penile reflex procedure to assess erectile function. Vz did not produce any gross maternal or neonatal toxicity, nor did it reduce the anogenital distance in male pups. We observed no effects of Vz on play behavior on PND22. However, the 12-mg/kg Vz dose significantly increased play behavior in the male offspring on PND34 compared with controls. The most dramatic increases were seen with the nape contact and pounce behavior components of play. The Vz effect was more pronounced in male than in female offspring. As adults, male offspring showed a significant reduction of erections at all dose levels during the ex copula penile reflex tests. The 12-mg/kg dose was also associated with an increase in seminal emissions. These effects demonstrate that perinatal Vz disrupts the development of androgen-mediated behavioral functions at exposure levels that do not produce obvious structural changes or weight reductions in androgen-sensitive reproductive organs. PMID:15929892

An introduction to differential equations using MATLAB

CERN Document Server

Butt, Rizwan

2016-01-01

An Introduction to Differential Equations using MATLAB exploits the symbolic, numerical, and graphical capabilitiesof MATLAB to develop a thorough understanding of differential equations algorithms. This book provides the readerwith numerous applications, m-files, and practical examples to problems. Balancing theoretical concepts withcomputational speed and accuracy, the book includes numerous short programs in MATLAB that can be used to solveproblems involving first-and higher-order differential equations, Laplace transforms, linear systems of differentialequations, numerical solutions of differential equations, computer graphics, and more. The author emphasizes thebasic ideas of analytical and numerical techniques and the uses of modern mathematical software (MATLAB) ratherthan relying only on complex mathematical derivations to engineers, mathematician, computer scientists, andphysicists or for use as a textbook in applied or computational courses.A CD-ROM with all the figures, codes, solutions, appendices...

How can GPS technology help us better understand exposure to the food environment? A systematic review

Directory of Open Access Journals (Sweden)

Andreea Cetateanu

2016-12-01

Full Text Available Purpose: Global Positioning Systems (GPS are increasingly being used to objectively assess movement patterns of people related to health behaviours. However research detailing their application to the food environment is scarce. This systematic review examines the application of GPS in studies of exposure to food environments and their potential influences on health. Methods: Based on an initial scoping exercise, published articles to be included in the systematic review were identified from four electronic databases and reference lists and were appraised and analysed, the final cut-off date for inclusion being January 2015. Included studies used GPS to identify location of individuals in relation to food outlets and link that to health or diet outcomes. They were appraised against a set of quality criteria. Results: Six studies met the inclusion criteria, which were appraised to be of moderate quality. Newer studies had a higher quality score. Associations between observed mobility patterns in the food environment and diet related outcomes were equivocal. Findings agreed that traditional food exposure measures overestimate the importance of the home food environment. Conclusions: The use of GPS to measure exposure to the food environment is still in its infancy yet holds much potential. There are considerable variations and challenges in developing and standardising the methods used to assess exposure. Keywords: Global positioning systems, Geographic information system, Food environments, Food exposure, Systematic review

Genome-wide expression analysis of human in vivo irritated epidermis: differential profiles induced by sodium lauryl sulfate and nonanoic acid.

Science.gov (United States)

Clemmensen, Anders; Andersen, Klaus E; Clemmensen, Ole; Tan, Qihua; Petersen, Thomas K; Kruse, Torben A; Thomassen, Mads

2010-09-01

The pathogenesis of irritant contact dermatitis (ICD) is poorly understood, and genes participating in the epidermal response to chemical irritants are only partly known. It is commonly accepted that different irritants have different mechanisms of action in the development of ICD. To define the differential molecular events induced in the epidermis by different irritants, we collected sequential biopsies ((1/2), 4, and 24 hours after a single exposure and at day 11 after repeated exposure) from human volunteers exposed to either sodium lauryl sulfate (SLS) or nonanoic acid (NON). Gene expression analysis using high-density oligonucleotide microarrays (representing 47,000 transcripts) revealed essentially different pathway responses (1/2)hours after exposure: NON transiently induced the IL-6 pathway as well as a number of mitogen-activated signaling cascades including extracellular signal-regulated kinase and growth factor receptor signaling, whereas SLS transiently downregulated cellular energy metabolism pathways. Differential expression of the cyclooxygenase-2 and matrix metalloproteinase 3 transcripts was confirmed immunohistochemically. After cumulative exposure, 883 genes were differentially expressed, whereas we identified 23 suggested common biomarkers for ICD. In conclusion, we bring new insights into two hitherto less well-elucidated phases of skin irritancy: the very initial as well as the late phase after single and cumulative mild exposures, respectively.

Reduction in DNA repair capacity following differentiation of murine proadipocytes

International Nuclear Information System (INIS)

Tofilon, P.J.; Meyn, R.E.

1988-01-01

It has been suggested that terminally differentiated mammalian cells have a decreased DNA repair capacity, compared with proliferating stem cells. To investigate this hypothesis, we have examined γ-ray-induced DNA strand breaks and their repair in the murine proadipocyte stem cell line 3T3-T. By exposure to human plasma, 3T3-T cells can be induced to undergo nonterminal and then terminal differentiation. DNA strand breaks were evaluated using the technique of alkaline elution. No difference was detected among stem, nonterminally differentiated, and terminally differentiated cells in the initial levels of radiation-induced DNA strand breaks. Each of the strand break dose responses increased as a linear function of γ-ray dose. The strand breaks induced by 4 Gy rejoined following biphasic kinetics for each cell type. At each time point examined after irradiation, however, the percentage of strand breaks that had not rejoined in terminally differentiated cells was three to six times greater than in stem cells. The rate of strand break rejoining in nonterminally differentiated cells was of an intermediate value between that of the stem and of the terminally differentiated cells. These results indicate that, at least for 3T3-T cells, differentiated cells have a reduced capacity for DNA repair

Two- and 4-hour bright-light exposures differentially effect sleepiness and performance the subsequent night.

Science.gov (United States)

Thessing, V C; Anch, A M; Muehlbach, M J; Schweitzer, P K; Walsh, J K

1994-03-01

The effect of two durations of bright light upon sleepiness and performance during typical night shift hours was assessed. Thirty normal, healthy young adults participated in a 2-night protocol. On the 1st night subjects were exposed to bright or dim light beginning at 2400 hours, under one of the following three conditions: bright light for 4 hours, dim light for 2 hours followed by bright light for 2 hours or dim light for 4 hours. Following light exposure, subjects remained awake until 0800 hours in a dimly lit room and slept in the laboratory between 0800 and 1600 hours, during which time sleep was estimated with actigraphy. Throughout the 2nd night, the multiple sleep latency test (MSLT), simulated assembly line task (SALT) performance, and subjective sleepiness were recorded. The single, 4-hour exposure to bright light was found to significantly increase MSLT scores and improve SALT performance during the early morning hours on the night following bright-light exposure. No significant effects were noted with a 2-hour exposure. The most likely explanation for these findings is a phase delay in the circadian rhythm of sleepiness-alertness.

Environmental chemical exposures and breast cancer

Directory of Open Access Journals (Sweden)

E. Stanley

2016-02-01

Full Text Available As a hormone-sensitive condition with no single identifiable cause, breast cancer is a major health problem. It is characterized by a wide range of contributing factors and exposures occurring in different combinations and strengths across a lifetime that may be amplified during periods of enhanced developmental susceptibility and impacted by reproductive patterns and behaviours. The vast majority of cases are oestrogen-receptor positive and occur in women with no family history of the disease suggesting that modifiable risk factors are involved. A substantial body of evidence now links oestrogen-positive breast cancer with environmental exposures. Synthetic chemicals capable of oestrogen mimicry are characteristic of industrial development and have been individually and extensively assessed as risk factors for oestrogen-sensitive cancers. Existing breast cancer risk assessment tools do not take such factors into account. In the absence of consensus on causation and in order to better understand the problem of escalating incidence globally, an expanded, integrated approach broadening the inquiry into individual susceptibility breast cancer is proposed. Applying systems thinking to existing data on oestrogen-modulating environmental exposures and other oestrogenic factors characteristic of Westernisation and their interactions in the exposure, encompassing social, behavioural, environmental, hormonal and genetic factors, can assist in understanding cancer risks and the pursuit of prevention strategies. A new conceptual framework based on a broader understanding of the “system” that underlies the development of breast cancer over a period of many years, incorporating the factors known to contribute to breast cancer risk, could provide a new platform from which government and regulators can promulgate enhanced and more effective prevention strategies.

In-depth 2-DE reference map of Aspergillus fumigatus and its proteomic profiling on exposure to itraconazole.

Science.gov (United States)

Gautam, Poonam; Mushahary, Dolly; Hassan, Wazid; Upadhyay, Santosh Kumar; Madan, Taruna; Sirdeshmukh, Ravi; Sundaram, Curam Sreenivasacharlu; Sarma, Puranam Usha

2016-07-01

Aspergillus fumigatus (A. fumigatus) is a medically important opportunistic fungus that may lead to invasive aspergillosis in humans with weak immune system. Proteomic profiling of this fungus on exposure to itraconazole (ITC), an azole antifungal drug, may lead to identification of its molecular targets and better understanding on the development of drug resistance against ITC in A. fumigatus. Here, proteome analysis was performed using 2-DE followed by mass spectrometric analysis which resulted in identification of a total of 259 unique proteins. Further, proteome profiling of A. fumigatus was carried out on exposure to ITC, 0.154 μg/ml, the minimum inhibitory concentration (MIC50). Image analysis showed altered levels of 175 proteins (66 upregulated and 109 downregulated) of A. fumigatus treated with ITC as compared to the untreated control. Peptide mass fingerprinting led to the identification of 54 proteins (12 up-regulated and 42 down-regulated). The differentially expressed proteins include proteins related to cell stress, carbohydrate metabolism and amino acid metabolism. We also observed four proteins, including nucleotide phosphate kinase (NDK), that are reported to interact with calcineurin, a protein involved in regulation of cell morphology and fungal virulence. Comparison of differentially expressed proteins on exposure to ITC with artemisinin (ART), an antimalarial drug with antifungal activity(1), revealed a total of 26 proteins to be common among them suggesting that common proteins and pathways are targeted by these two antifungal agents. The proteins targeted by ITC may serve as important leads for development of new antifungal drugs. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fluoxetine Induces Proliferation and Inhibits Differentiation of Hypothalamic Neuroprogenitor Cells In Vitro

Science.gov (United States)

Sousa-Ferreira, Lígia; Aveleira, Célia; Botelho, Mariana; Álvaro, Ana Rita; Pereira de Almeida, Luís; Cavadas, Cláudia

2014-01-01

A significant number of children undergo maternal exposure to antidepressants and they often present low birth weight. Therefore, it is important to understand how selective serotonin reuptake inhibitors (SSRIs) affect the development of the hypothalamus, the key center for metabolism regulation. In this study we investigated the proliferative actions of fluoxetine in fetal hypothalamic neuroprogenitor cells and demonstrate that fluoxetine induces the proliferation of these cells, as shown by increased neurospheres size and number of proliferative cells (Ki-67+ cells). Moreover, fluoxetine inhibits the differentiation of hypothalamic neuroprogenitor cells, as demonstrated by decreased number of mature neurons (Neu-N+ cells) and increased number of undifferentiated cells (SOX-2+ cells). Additionally, fluoxetine-induced proliferation and maintenance of hypothalamic neuroprogenitor cells leads to changes in the mRNA levels of appetite regulator neuropeptides, including Neuropeptide Y (NPY) and Cocaine-and-Amphetamine-Regulated-Transcript (CART). This study provides the first evidence that SSRIs affect the development of hypothalamic neuroprogenitor cells in vitro with consequent alterations on appetite neuropeptides. PMID:24598761

Pathologic bladder microenvironment attenuates smooth muscle differentiation of skin derived precursor cells: implications for tissue regeneration.

Directory of Open Access Journals (Sweden)

Cornelia Tolg

Full Text Available Smooth muscle cell containing organs (bladder, heart, blood vessels are damaged by a variety of pathological conditions necessitating surgery or organ replacement. Currently, regeneration of contractile tissues is hampered by lack of functional smooth muscle cells. Multipotent skin derived progenitor cells (SKPs can easily be isolated from adult skin and can be differentiated in vitro into contractile smooth muscle cells by exposure to FBS. Here we demonstrate an inhibitory effect of a pathologic contractile organ microenvironment on smooth muscle cell differentiation of SKPs. In vivo, urinary bladder strain induces microenvironmental changes leading to de-differentiation of fully differentiated bladder smooth muscle cells. Co-culture of SKPs with organoids isolated from ex vivo stretched bladders or exposure of SKPs to diffusible factors released by stretched bladders (e.g. bFGF suppresses expression of smooth muscle markers (alpha SMactin, calponin, myocardin, myosin heavy chain as demonstrated by qPCR and immunofluorescent staining. Rapamycin, an inhibitor of mTOR signalling, previously observed to prevent bladder strain induced de-differentiation of fully differentiated smooth muscle cells in vitro, inhibits FBS-induced smooth muscle cell differentiation of undifferentiated SKPs. These results suggest that intended precursor cell differentiation may be paradoxically suppressed by the disease context for which regeneration may be required. Organ-specific microenvironment contexts, particularly prevailing disease, may play a significant role in modulating or attenuating an intended stem cell phenotypic fate, possibly explaining the variable and inefficient differentiation of stem cell constructs in in vivo settings. These observations must be considered in drafting any regeneration strategies.

The Screening of Genes Sensitive to Long-Term, Low-Level Microwave Exposure and Bioinformatic Analysis of Potential Correlations to Learning and Memory

Institute of Scientific and Technical Information of China (English)

ZHAO Ya Li; LI Ying Xian; MA Hong Bo; LI Dong; LI Hai Liang; JIANG Rui; KAN Guang Han; YANG Zhen Zhong; HUANG Zeng Xin

2015-01-01

Objective To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction. Methods Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR. Results The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memory. Conclusion Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases.

Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

International Nuclear Information System (INIS)

Chen, Qi-Liang; Luo, Zhi; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

2013-01-01

Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

Energy Technology Data Exchange (ETDEWEB)

Chen, Qi-Liang; Luo, Zhi, E-mail: luozhi99@yahoo.com.cn; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

2013-07-15

Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

Industrial chemical exposure: guidelines for biological monitoring

National Research Council Canada - National Science Library

Lauwerys, Robert R; Hoet, Perrine

2001-01-01

.... With Third Edition of Industrial Chemical Exposure you will understand the objectives of biological monitoring, the types of biological monitoring methods, their advantages and limitations, as well...

Differential diagnosis of radiation injury

Energy Technology Data Exchange (ETDEWEB)

Wendt, F

1971-04-01

A single haematological alteration is not sufficient to diagnose whether it is a radiation-induced change or not. For the differential diagnosis of possibly radiation-induced changes in the peripheral blood and blood-forming organs, information on the radiation exposure in terms of time, quality, quantity and localization, and the clinical symptoms have to be taken into account. Ionizing radiation within the dosage range considered here produces cell division delay, mitotic inhibition, chromosomal damage or interphase cell death; it thereby interferes with the steady-state equilibria in the cell-renewal systems of the organism (Bond et al., 1965; Little, 1968). The cause of haematological changes appearing immediately after a short-term, external whole-body radiation exposure has been described and analysed elsewhere in this Manual. The critical cell component is the 'stem cell compartment' which is highly radiosensitive and suffers damage but, because stem cells cannot be identified morphologically, a direct study of stem cell injury is not possible.

MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells

Directory of Open Access Journals (Sweden)

Pai-Chi Tsai

2014-07-01

Full Text Available Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3′UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development.

Secreted Frizzled related protein-4 (sFRP4) promotes epidermal differentiation and apoptosis

International Nuclear Information System (INIS)

Maganga, Richard; Giles, Natalie; Adcroft, Katharine; Unni, Ambili; Keeney, Diane; Wood, Fiona; Fear, Mark; Dharmarajan, Arunasalam

2008-01-01

The skin provides vital protection from infection and dehydration. Maintenance of the skin is through a constant program of proliferation, differentiation and apoptosis of epidermal cells, whereby proliferating cells in the basal layer differentiating to form the keratinized, anucleated stratum corneum. The WNT signalling pathway is known to be important in the skin. WNT signalling has been shown to be important both in epidermal development and in the maintenance and cycling of hair follicles and epidermal stem cells. However, the precise role for this pathway in epidermal differentiation remains unknown. We investigated the role of the WNT signalling inhibitor sFRP4 in epidermal differentiation. sFRP4 is expressed in both normal skin and keratinocytes in culture. Expression of sFRP4 mRNA and protein increases with keratinocyte differentiation and apoptosis, whilst exposure of keratinocytes to exogenous sFRP4 promotes apoptosis and expression of the terminal differentiation marker Involucrin. These data suggest sFRP4 promotes epidermal differentiation.

In vitro study on chromosomal abnormality, proliferation and differentiation of hemopoietic stem cells from atomic bomb exposures and patients with acute leukemia and related disorders

Energy Technology Data Exchange (ETDEWEB)

Amenomori, Tatsuhiko

1988-12-01

By using in vitro cloning method and cytogenetic analysis from single hemopoietic colonies, the kinetics of differentiation and proliferation, and chromosomal abnormalities of hemopoietic stem cells (CFU-GM, BFU-E) from atomic bomb exposures and patients with acute leukemia and myelodysplastic syndrome (MDS) were investigated. High incidence (24 colonies/ 206 total colonies; 11.7%) of irradiation-induced chromosomal abnormalities was observed in circulating hemopoietic stem cells from 21 high dose exposures. In two individuals, karyotypic abnormalities closely resembling those observed in the peripheral T lymphocytes were also seen in the myeloid stem cells (BFU-E). This finding suggests that totipotential stem cells common to myeloid and lymphoid lineages exist in healthy human adults and atomic bomb irradiation produced chromosomal aberrations in them. In each of 5 MDS cases with both GM colony and erythroid burst formation, identical marker chromosomes were seen in CFU-GM and BFU-E. This finding demonstrates that MDS is a clonal hemopathy that originates in a pluripotential stem cell. Whether acute leukemia is also a clonal hemopathy originating in a pluripotential stem cell remains to be determined. But there was a considerable heterogeneity in kinetics of proliferation and in responsiveness to colony stimulating factors among these cases. (author) 54 refs.

Understanding of radiation protection in medicine. Pt. 1. Knowledge about radiation exposure and anxiety about radiation injury

International Nuclear Information System (INIS)

Iida, Hiroji; Yamamoto, Tomoyuki; Shimada, Yasuhiro

1997-01-01

Using a questionnaire we investigated whether radiation exposure in correctly understood by medical doctors (n=140), nurses (n=496) and the general public (n=236). Thirty-three percent of medical doctors, 53% of nurses and the general public did not know who is legally allowed to irradiate the human body. Forty-five percent of doctors, 63% of nurses and 48% of the general public complained of anxiety about radiation injury. Fifty-six percent of patients did not ask medical doctors or nurses for an explanation of the risk of exposure. Moreover, 64% of doctors did not explain the risk to patients. In addition, 21% of doctors, 46% of nurses and the general public incorrectly understood that x-rays remain in the examination room. Twenty-seven percent of doctors, 49% of nurses and 80% of the general public did not know the t en-day rule . In conclusion, the results of this questionnaire indicated that basic knowledge about radiation exposure was not adequate. To protect against medical radiation exposure, personnel who are licensed to irradiate to the human body should be well recognized by medical staff and the general public. It is also important that informed consent for radiological examinations be based on fundamental knowledge about radiation exposure. Therefore, to reach a general consensus on radiological examinations and to reduce individual exposure, general public education regarding radiation protection is required. Postgraduate education on radiation protection for medical doctors and nurses is also strongly recommended. (author)

Development of a Job-Exposure Matrix (AsbJEM) to Estimate Occupational Exposure to Asbestos in Australia.

Science.gov (United States)

van Oyen, Svein C; Peters, Susan; Alfonso, Helman; Fritschi, Lin; de Klerk, Nicholas H; Reid, Alison; Franklin, Peter; Gordon, Len; Benke, Geza; Musk, Arthur W

2015-07-01

Occupational exposure data on asbestos are limited and poorly integrated in Australia so that estimates of disease risk and attribution of disease causation are usually calculated from data that are not specific for local conditions. To develop a job-exposure matrix (AsbJEM) to estimate occupational asbestos exposure levels in Australia, making optimal use of the available exposure data. A dossier of all available exposure data in Australia and information on industry practices and controls was provided to an expert panel consisting of three local industrial hygienists with thorough knowledge of local and international work practices. The expert panel estimated asbestos exposures for combinations of occupation, industry, and time period. Intensity and frequency grades were estimated to enable the calculation of annual exposure levels for each occupation-industry combination for each time period. Two indicators of asbestos exposure intensity (mode and peak) were used to account for different patterns of exposure between occupations. Additionally, the probable type of asbestos fibre was determined for each situation. Asbestos exposures were estimated for 537 combinations of 224 occupations and 60 industries for four time periods (1943-1966; 1967-1986; 1987-2003; ≥2004). Workers in the asbestos manufacturing, shipyard, and insulation industries were estimated to have had the highest average exposures. Up until 1986, 46 occupation-industry combinations were estimated to have had exposures exceeding the current Australian exposure standard of 0.1 f ml(-1). Over 90% of exposed occupations were considered to have had exposure to a mixture of asbestos varieties including crocidolite. The AsbJEM provides empirically based quantified estimates of asbestos exposure levels for Australian jobs since 1943. This exposure assessment application will contribute to improved understanding and prediction of asbestos-related diseases and attribution of disease causation. © The

Ability to Discriminate Between Sustainable and Unsustainable Heat Stress Exposures-Part 1: WBGT Exposure Limits.

Science.gov (United States)

Garzón-Villalba, Ximena P; Wu, Yougui; Ashley, Candi D; Bernard, Thomas E

2017-07-01

Heat stress exposure limits based on wet-bulb globe temperature (WBGT) were designed to limit exposures to those that could be sustained for an 8-h day using limited data from Lind in the 1960s. In general, Sustainable exposures are heat stress levels at which thermal equilibrium can be achieved, and Unsustainable exposures occur when there is a steady increase in core temperature. This paper addresses the ability of the ACGIH® Threshold Limit Value (TLV®) to differentiate between Sustainable and Unsustainable heat exposures, to propose alternative occupational exposure limits, and ask whether an adjustment for body surface area improves the exposure decision. Two progressive heat stress studies provided data on 176 trials with 352 pairs of Sustainable and Unsustainable exposures over a range of relative humidities and metabolic rates using 29 participants wearing woven cotton clothing. To assess the discrimination ability of the TLV, the exposure metric was the difference between the observed WBGT and the TLV adjusted for metabolic rate. Conditional logistic regression models and receiver operating characteristic curves (ROC) along with ROC's area under the curve (AUC) were used. Four alternative models for an occupational exposure limit were also developed and compared to the TLV. For the TLV, the odds ratio (OR) for Unsustainable was 2.5 per 1°C-WBGT [confidence interval (CI) 2.12-2.88]. The AUC for the TLV was 0.85 (CI 0.81-0.89). For the alternative models, the ORs were also about 2.5/°C-WBGT, with AUCs between 0.84 and 0.88, which were significantly different from the TLV's AUC but have little practical difference. This study (1) confirmed that the TLV is appropriate for heat stress screening; (2) demonstrated the TLV's discrimination accuracy with an ROC AUC of 0.85; and (3) established the OR of 2.5/°C-WBGT for unsustainable exposures. The TLV has high sensitivity, but its specificity is very low, which is protective. There were no important

Differential calculus in normed linear spaces

CERN Document Server

Mukherjea, Kalyan

2007-01-01

This book presents Advanced Calculus from a geometric point of view: instead of dealing with partial derivatives of functions of several variables, the derivative of the function is treated as a linear transformation between normed linear spaces. Not only does this lead to a simplified and transparent exposition of "difficult" results like the Inverse and Implicit Function Theorems but also permits, without any extra effort, a discussion of the Differential Calculus of functions defined on infinite dimensional Hilbert or Banach spaces.The prerequisites demanded of the reader are modest: a sound understanding of convergence of sequences and series of real numbers, the continuity and differentiability properties of functions of a real variable and a little Linear Algebra should provide adequate background for understanding the book. The first two chapters cover much of the more advanced background material on Linear Algebra (like dual spaces, multilinear functions and tensor products.) Chapter 3 gives an ab ini...

Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency

Directory of Open Access Journals (Sweden)

Yufen Xie

2014-11-01

Full Text Available Dysfunctional stem cell differentiation into placental lineages is associated with gestational diseases. Of the differentiated lineages available to trophoblast stem cells (TSC, elevated O2 and mitochondrial function are necessary to placental lineages at the maternal–placental surface and important in the etiology of preeclampsia. TSC lineage imbalance leads to embryonic failure during uterine implantation. Stress at implantation exacerbates stem cell depletion by decreasing proliferation and increasing differentiation. In an implantation site O2 is normally ~2%. In culture, exposure to 2% O2 and fibroblast growth factor 4 (FGF4 enabled the highest mouse TSC multipotency and proliferation. In contrast, hypoxic stress (0.5% O2 initiated the most TSC differentiation after 24 h despite exposure to FGF4. However, hypoxic stress supported differentiation poorly after 4–7 days, despite FGF4 removal. At all tested O2 levels, FGF4 maintained Warburg metabolism; mitochondrial inactivity and aerobic glycolysis. However, hypoxic stress suppressed mitochondrial membrane potential and maintained low mitochondrial cytochrome c oxidase (oxidative phosphorylation/OxPhos, and high pyruvate kinase M2 (glycolysis despite FGF4 removal. Inhibiting OxPhos inhibited optimum differentiation at 20% O2. Moreover, adding differentiation-inducing hyperosmolar stress failed to induce differentiation during hypoxia. Thus, differentiation depended on OxPhos at 20% O2; hypoxic and hyperosmolar stresses did not induce differentiation at 0.5% O2. Hypoxia-limited differentiation and mitochondrial inhibition and activation suggest that differentiation into two lineages of the labyrinthine placenta requires O2 > 0.5–2% and mitochondrial function. Stress-activated protein kinase increases an early lineage and suppresses later lineages in proportion to the deviation from optimal O2 for multipotency, thus it is the first enzyme reported to prioritize differentiation.

The Exposure Advantage: Early Exposure to a Multilingual Environment Promotes Effective Communication.

Science.gov (United States)

Fan, Samantha P; Liberman, Zoe; Keysar, Boaz; Kinzler, Katherine D

2015-07-01

Early language exposure is essential to developing a formal language system, but may not be sufficient for communicating effectively. To understand a speaker's intention, one must take the speaker's perspective. Multilingual exposure may promote effective communication by enhancing perspective taking. We tested children on a task that required perspective taking to interpret a speaker's intended meaning. Monolingual children failed to interpret the speaker's meaning dramatically more often than both bilingual children and children who were exposed to a multilingual environment but were not bilingual themselves. Children who were merely exposed to a second language performed as well as bilingual children, despite having lower executive-function scores. Thus, the communicative advantages demonstrated by the bilinguals may be social in origin, and not due to enhanced executive control. For millennia, multilingual exposure has been the norm. Our study shows that such an environment may facilitate the development of perspective-taking tools that are critical for effective communication. © The Author(s) 2015.

RAMAN SPECTROSCOPY-BASED METABOLOMICS FOR DIFFERENTIATING EXPOSURES TO TRIAZOLE FUNGICIDES USING RAT URINE

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Normal Raman spectroscopy was evaluated as a metabolomic tool for assessing the impacts of exposure to environmental contaminants, using rat urine collected during the course of a toxicological study. Specifically, one of three triazole fungicides, myclobutanil, propiconazole or ...

Di (2-ethylhexyl Phthalate Exposure Impairs Growth of Antral Follicle in Mice.

Directory of Open Access Journals (Sweden)

Lan Li

Full Text Available Di (2-ethylhexyl phthalate (DEHP is a widely used plastic additive. As an environmental endocrine disruptor, it has been shown to be harmful to the mammalian reproductive system. Previous studies indicated that DEHP inhibited the development of mouse ovarian follicles. However, the mechanisms by which DEHP affects ovarian antral follicle development during the pre-puberty stage are poorly understand. Thus, we investigated the effects of direct DEHP exposure on antral follicle growth in pre-pubescent mice by use of intraperitoneal injection. Our results demonstrated that the percentage of large antral follicles was significantly reduced when mice were exposed to 20 or 40 μg/kg DEHP every 5 days from postnatal day 0 (0 dpp to 15 dpp. In 20 dpp, we performed microarray of these ovaries. The microarray results indicated that mRNA levels of apoptosis related genes were increased. The mRNA levels of the apoptosis and cell proliferation (negative related genes Apoe, Agt, Glo1 and Grina were increased after DEHP exposure. DEHP induced the differential gene expression of Hsp90ab1, Rhoa, Grina and Xdh which may play an important role in this process. In addition, TUNEL staining and immunofluorescence showed that DEHP exposure significantly increased the number of TUNEL, Caspase3 and γH2AX positive ovarian somatic cells within the mouse ovaries. Flow cytometer analyses of redox-sensitive probes showed that DEHP caused the accumulation of reactive oxygen species. Moreover, the mRNA expression of ovarian somatic cell antioxidative enzymes was down-regulated both in vivo and in vitro. In conclusion, our data here demonstrated that DEHP exposure induced oxidative stress and ovarian somatic cell apoptosis, and thus may impact antral follicle enlargement during the pre-pubertal stage in mice.

Characterization of the inhibitory effect of growth hormone on primary preadipocyte differentiation

DEFF Research Database (Denmark)

Hansen, L. H.; Madsen, B; Teisner, Børge

1998-01-01

GH exerts adipogenic activity in several preadipocyte cell lines, whereas in primary rat preadipocytes, GH has an antiadipogenic activity. To better understand the molecular mechanism involved in adipocyte differentiation, the expression of adipocyte-specific genes was analyzed in differentiating...

Chronic neonicotinoid pesticide exposure and parasite stress differentially affects learning in honeybees and bumblebees.

Science.gov (United States)

Piiroinen, Saija; Goulson, Dave

2016-04-13

Learning and memory are crucial functions which enable insect pollinators to efficiently locate and extract floral rewards. Exposure to pesticides or infection by parasites may cause subtle but ecologically important changes in cognitive functions of pollinators. The potential interactive effects of these stressors on learning and memory have not yet been explored. Furthermore, sensitivity to stressors may differ between species, but few studies have compared responses in different species. Here, we show that chronic exposure to field-realistic levels of the neonicotinoid clothianidin impaired olfactory learning acquisition in honeybees, leading to potential impacts on colony fitness, but not in bumblebees. Infection by the microsporidian parasite Nosema ceranae slightly impaired learning in honeybees, but no interactive effects were observed. Nosema did not infect bumblebees (3% infection success). Nevertheless, Nosema-treated bumblebees had a slightly lower rate of learning than controls, but faster learning in combination with neonicotinoid exposure. This highlights the potential for complex interactive effects of stressors on learning. Our results underline that one cannot readily extrapolate findings from one bee species to others. This has important implications for regulatory risk assessments which generally use honeybees as a model for all bees. © 2016 The Author(s).

Chronic neonicotinoid pesticide exposure and parasite stress differentially affects learning in honeybees and bumblebees

Science.gov (United States)

2016-01-01

Learning and memory are crucial functions which enable insect pollinators to efficiently locate and extract floral rewards. Exposure to pesticides or infection by parasites may cause subtle but ecologically important changes in cognitive functions of pollinators. The potential interactive effects of these stressors on learning and memory have not yet been explored. Furthermore, sensitivity to stressors may differ between species, but few studies have compared responses in different species. Here, we show that chronic exposure to field-realistic levels of the neonicotinoid clothianidin impaired olfactory learning acquisition in honeybees, leading to potential impacts on colony fitness, but not in bumblebees. Infection by the microsporidian parasite Nosema ceranae slightly impaired learning in honeybees, but no interactive effects were observed. Nosema did not infect bumblebees (3% infection success). Nevertheless, Nosema-treated bumblebees had a slightly lower rate of learning than controls, but faster learning in combination with neonicotinoid exposure. This highlights the potential for complex interactive effects of stressors on learning. Our results underline that one cannot readily extrapolate findings from one bee species to others. This has important implications for regulatory risk assessments which generally use honeybees as a model for all bees. PMID:27053744

Transcriptional and epigenetic mechanisms underlying enhanced in vitro adipocyte differentiation by the brominated flame retardant BDE-47

DEFF Research Database (Denmark)

Kamstra, Jorke H; Hruba, Eva; Blumberg, Bruce

2014-01-01

Recent studies suggest that exposure to endocrine-disrupting compounds (EDCs) may play a role in the development of obesity. EDCs such as the flame retardant 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) have been shown to enhance adipocyte differentiation in the murine 3T3-L1 model. The mech......Recent studies suggest that exposure to endocrine-disrupting compounds (EDCs) may play a role in the development of obesity. EDCs such as the flame retardant 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) have been shown to enhance adipocyte differentiation in the murine 3T3-L1 model....... The mechanisms by which EDCs direct preadipocytes to form adipocytes are poorly understood. Here, we examined transcriptional and epigenetic mechanisms underlying the induction of in vitro adipocyte differentiation by BDE-47. Quantitative high content microscopy revealed concentration-dependent enhanced...

Cell cycle sensitivity of HL-60 cells to the differentiation-inducing effects of 1-alpha,25-dihydroxyvitamin D3

International Nuclear Information System (INIS)

Studzinski, G.P.; Bhandal, A.K.; Brelvi, Z.S.

1985-01-01

A recently described system for monocyte-like differentiation of HL-60 cells was utilized to determine if the initiation of this pathway can be linked to a set of replicative cellular events. The standard induction system consisted of a 4-h exposure to 100 nM 1-alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] followed by determination of nonspecific esterase and phagocytic activity 24 h later. The cell cycle status was ascertained by the incorporation of [ 3 H]thymidine and autoradiography. Studies in which cell cycle block in the G1/S phase boundary region was produced by a partial inhibition of DNA synthesis with thymidine, or sodium butyrate, showed that the exposure of such semisynchronous cultures to 1,25(OH)2D3 resulted in an increased proportion of differentiated cells. Conversely, blocking the cell cycle with vinblastine (G2/M block) or theobromine (mid-G1 block) inhibited the initiation of differentiation by 1,25(OH)2D3. Experiments in which the differentiated cells were examined for the cell cycle position at the time of the exposure to 1,25(OH)2D3 by [ 3 H]thymidine labeling and autoradiography confirmed that the late G1 and early S phase cells are those which predominate in the differentiated fraction of 1,25(OH)2D3-treated HL-60 cultures. These results link pre- and early replicative cellular events to the induction of monocytic differentiation by 1,25(OH)2D3

Adolescent alcohol exposure: Are there separable vulnerable periods within adolescence?

Science.gov (United States)

Spear, Linda Patia

2015-09-01

There are two key alcohol use patterns among human adolescents that confer increased vulnerability for later alcohol abuse/dependence, along with neurocognitive alterations: (a) early initiation of use during adolescence, and (b) high rates of binge drinking that are particularly prevalent late in adolescence. The central thesis of this review is that lasting neurobehavioral outcomes of these two adolescent exposure patterns may differ. Although it is difficult to disentangle consequences of early use from later binge drinking in human studies given the substantial overlap between groups, these two types of problematic adolescent use are differentially heritable and hence separable to some extent. Although few studies using animal models have manipulated alcohol exposure age, those studies that have have typically observed timing-specific exposure effects, with more marked (or at least different patterns of) lasting consequences evident after exposures during early-mid adolescence than late-adolescence/emerging adulthood, and effects often restricted to male rats in those few instances where sex differences have been explored. As one example, adult male rats exposed to ethanol during early-mid adolescence (postnatal days [P] 25-45) were found to be socially anxious and to retain adolescent-typical ethanol-induced social facilitation into adulthood, effects that were not evident after exposure during late-adolescence/emerging adulthood (P45-65); exposure at the later interval, however, induced lasting tolerance to ethanol's social inhibitory effects that was not evident after exposure early in adolescence. Females, in contrast, were little influenced by ethanol exposure at either interval. Exposure timing effects have likewise been reported following social isolation as well as after repeated exposure to other drugs such as nicotine (and cannabinoids), with effects often, although not always, more pronounced in males where studied. Consistent with these timing

Adverse effects of perinatal nicotine exposure on reproductive outcomes.

Science.gov (United States)

Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

2015-12-01

Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women. © 2015 Society for Reproduction and Fertility.

[Low-frequency pulsed electromagnetic fields promotes rat osteoblast differentiation in vitro through cAMP/PKA signal pathway].

Science.gov (United States)

Fang, Qing-Qing; Li, Zhi-Zhong; Zhou, Jian; Shi, Wen-Gui; Yan, Juan-Li; Xie, Yan-Fang; Chen, Ke-Ming

2016-11-20

To study whether low-frequency pulsed electromagnetic fields promotes the differentiation of cultured rat osteoblasts through the cAMP/PKA signal pathway. Rat calvarial osteoblasts isolated by enzyme digestion were exposed to 50 Hz 0.6 mT low-frequency pulsed electromagnetic field for varying lengths of time, and the concentration of cAMP and levels of phosphorylated PKA in the cells were assayed. In cells treated with DDA to inhibit the activity of adenylate cyclase, the changes of ALP activity and transcription of osteogenic gene were detected after exposure to low-frequency pulsed electromagnetic field. The changes of osteogenic gene transcription and protein expression were tested in the osteoblasts pretreated with KT5720 in response to low-frequency pulsed electromagnetic field exposure. The intracellular cAMP concentration in the cells increased significantly at 20 min during exposure to low-frequency pulsed electromagnetic field, began to decrease at 40 min during the exposure, and increased again after a 2-h exposure; the same pattern of variation was also observed in p-PKA level. Application of DDA and KT5720 pretreatment both suppressed the increase in ALP activity and osteogenic gene transcription induced by electromagnetic field exposure. Low- frequency pulsed electromagnetic field exposure improves the differentiation of cultured rat osteoblasts by activating cAMP/PKA signal pathway.

Corneal Toxicity Following Exposure to Asclepias Tuberosa.

Science.gov (United States)

Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; Gül, Cigdem Altuntas; Heegaard, Steffen

2017-01-01

To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa. A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa . Clinical examination revealed a corneal stromal oedema with small epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine. The corneal oedema had appeared after corneal exposure to the plant, Asclepias tuberosa , whose latex contains cardenolides that inhibit the Na + / K + -ATPase in the corneal endothelium. The oedema resolved after 96 hours. After nine months the best corrected visual acuity was 20/20. Corneal toxicity has previously been reported for plants of the Asclepias family. This is a rare case describing severe corneal toxicity caused by exposure to latex from Asclepias tuberosa . Handling of plants of the Asclepias family should be kept as a differential diagnosis in cases of acute corneal toxicity.

Troubled or Traumatized Youth? The Relations Between Psychopathy, Violence Exposure, Posttraumatic Stress Disorder, and Antisocial Behavior Among Juvenile Offenders.

Science.gov (United States)

Tsang, Siny

2018-01-01

The current study examined how psychopathy, exposure to violence, and posttraumatic stress disorder (PTSD) are associated with antisocial behavior among 1,354 serious delinquent adolescents from the Pathways to Desistance study. Results showed that psychopathy, violence exposure, and PTSD are independently linked to self-reported involvement of delinquency, even after controlling for respondents' demographic characteristics. However, the effect of PTSD on antisocial behavior was small. Differential associations were observed between the 2 factors of psychopathy, interpersonal/affective and social deviance, and PTSD symptoms. Specifically, the effect of social deviance characteristics on delinquency was above and beyond that of interpersonal/affective features. In addition, exposure to violence as a victim or witness were uniquely associated with increased delinquent behavior. Findings clarified the relations among psychopathy, violence exposure, PTSD, and antisocial behavior, and highlighted the differential links between psychopathy factors and delinquency.

Exposure science in an age of rapidly changing climate: challenges and opportunities

Science.gov (United States)

LaKind, Judy S; Overpeck, Jonathan; Breysse, Patrick N; Backer, Lorrie; Richardson, Susan D; Sobus, Jon; Sapkota, Amir; Upperman, Crystal R; Jiang, Chengsheng; Beard, C Ben; Brunkard, J M; Bell, Jesse E; Harris, Ryan; Chretien, Jean-Paul; Peltier, Richard E; Chew, Ginger L; Blount, Benjamin C

2016-01-01

Climate change is anticipated to alter the production, use, release, and fate of environmental chemicals, likely leading to increased uncertainty in exposure and human health risk predictions. Exposure science provides a key connection between changes in climate and associated health outcomes. The theme of the 2015 Annual Meeting of the International Society of Exposure Science—Exposures in an Evolving Environment—brought this issue to the fore. By directing attention to questions that may affect society in profound ways, exposure scientists have an opportunity to conduct “consequential science”—doing science that matters, using our tools for the greater good and to answer key policy questions, and identifying causes leading to implementation of solutions. Understanding the implications of changing exposures on public health may be one of the most consequential areas of study in which exposure scientists could currently be engaged. In this paper, we use a series of case studies to identify exposure data gaps and research paths that will enable us to capture the information necessary for understanding climate change-related human exposures and consequent health impacts. We hope that paper will focus attention on under-developed areas of exposure science that will likely have broad implications for public health. PMID:27485992

Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

Energy Technology Data Exchange (ETDEWEB)

Biemann, Ronald, E-mail: ronald.biemann@medizin.uni-halle.de [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany); Navarrete Santos, Anne [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany); Navarrete Santos, Alexander [Department of Cardiothoracic Surgery, Martin Luther University, Faculty of Medicine, Halle (Germany); Riemann, Dagmar [Department of Immunology, Martin Luther University, Faculty of Medicine, Halle (Germany); Knelangen, Julia [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany); Blueher, Matthias [Department of Medicine, University of Leipzig, Leipzig (Germany); Koch, Holger [Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Ruhr-University Bochum, Bochum (Germany); Fischer, Bernd [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany)

2012-01-13

Highlights: Black-Right-Pointing-Pointer Endocrine disrupting chemicals affect adipogenesis in mesenchymal stem cells (MSC). Black-Right-Pointing-Pointer The adipogenic impact depends strongly on the window of exposure. Black-Right-Pointing-Pointer Bisphenol A reduces the potential of MSC to differentiate into adipocytes. Black-Right-Pointing-Pointer DEHP and TBT trigger the adipogenic differentiation of mesenchymal stem cells. Black-Right-Pointing-Pointer BPA, DEHP and TBT did not affect adipogenesis in embryonic stem cells. -- Abstract: Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPAR{gamma}2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 {mu}M) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 {mu}M) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

International Nuclear Information System (INIS)

Biemann, Ronald; Navarrete Santos, Anne; Navarrete Santos, Alexander; Riemann, Dagmar; Knelangen, Julia; Blüher, Matthias; Koch, Holger; Fischer, Bernd

2012-01-01

Highlights: ► Endocrine disrupting chemicals affect adipogenesis in mesenchymal stem cells (MSC). ► The adipogenic impact depends strongly on the window of exposure. ► Bisphenol A reduces the potential of MSC to differentiate into adipocytes. ► DEHP and TBT trigger the adipogenic differentiation of mesenchymal stem cells. ► BPA, DEHP and TBT did not affect adipogenesis in embryonic stem cells. -- Abstract: Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPARγ2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 μM) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 μM) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

Why did adolescents have sleep problems after earthquakes? Understanding the role of traumatic exposure, fear, and PTSD.

Science.gov (United States)

Zhou, Xiao; Wu, Xinchun; Chen, Qiuyan; Zhen, Rui

2017-06-01

To examine the relationships between trauma exposure, fear, post-traumatic stress disorder, and sleep problems in adolescents, 746 adolescent survivors of the 2008 Wenchuan earthquake in China were assessed at 1 year (T1) and 1.5 years (T2) after the earthquake using a trauma exposure questionnaire, a fear questionnaire, a child posttraumatic stress disorder symptom scale, and a subscale on child sleep problems. The results showed that T1 trauma exposure were not directly associated with sleep problems at T1 and T2, but played a positive role in sleep problems at both T1 and T2 indirectly through T1 posttraumatic stress disorder and T1 fear. T1 trauma exposure was also positively and indirectly associated with T2 sleep problems through T1 posttraumatic stress disorder via T1 sleep problems, or through T1 fear via the path from T1 posttraumatic stress disorder to T1 sleep problems. These findings indicated that fear and posttraumatic stress disorder 1 year after the earthquake played a mediating role in the relationship between trauma exposure at 1 year after the earthquake, and sleep problems at both 1 year and 1.5 years after the earthquake, respectively. In particular, posttraumatic stress disorder also had a multiple mediating effect in the path from trauma exposure to sleep problems via fear. Furthermore, the findings indicated that sleep problems were relatively stable between 1 and 1.5 years after an earthquake. © 2017 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

The differential susceptibility to media effects model

NARCIS (Netherlands)

Valkenburg, P.M.; Peter, J.

2013-01-01

In this theoretical article, we introduce the Differential Susceptibility to Media Effects Model (DSMM), a new, integrative model to improve our understanding of media effects. The DSMM organizes, integrates, and extends the insights developed in earlier microlevel media-effects theories. It

Rho GTPases in ameloblast differentiation

Directory of Open Access Journals (Sweden)

Keishi Otsu

2016-05-01

Full Text Available During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating epithelial–mesenchymal interaction and a cell-autonomous gene network. The differentiation process of epithelial cells is characterized by marked changes in their morphology and polarity, accompanied by dynamic cytoskeletal reorganization and changes in cell–cell and cell–matrix adhesion over time. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete enamel-specific proteins. After deposition of the full thickness of enamel matrix, ameloblasts become smaller and regulate enamel maturation. Recent significant advances in the fields of molecular biology and genetics have improved our understanding of the regulatory mechanism of the ameloblast cell life cycle, mediated by the Rho family of small GTPases. They act as intracellular molecular switch that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus. In our review, we summarize studies that provide current evidence for Rho GTPases and their involvement in ameloblast differentiation. In addition to the Rho GTPases themselves, their downstream effectors and upstream regulators have also been implicated in ameloblast differentiation.

Effect of low and chronic radiation exposure to human population: Kollam study

International Nuclear Information System (INIS)

Ghosh, Anu; Kumar, Vinay

2018-01-01

Understanding the cellular and biological processes with low-level chronic radiation provides a rational basis for limits of exposure for occupational workers and general public. There are several high level natural radiation areas (HLNRA) of the world where human population is continuously exposed to natural radiation higher than the global average of 2.4 mGy/y. These areas provide unique opportunities to conduct studies which can provide better understanding of radiation effects and underlying mechanisms. The ∼55 km long monazite bearing belt of Kerala on the south-west coast of India is one such area. Over the last few decades, Bhabha Atomic Research Centre (BARC) has conducted extensive research on the human population residing in these areas to understand effects of low dose at the organismal, cellular and molecular levels. More recently, high resolution quantitative proteomic analysis of PBMCs using iTRAQ based LC-MS/MS identified differential expression of 1570 proteins in HLNRA individuals relative to individuals from the adjoining Normal Level Natural Radiation Areas (NLNRA). Almost 215 biological processes were distinctly altered in HLNRA samples, which included several pro-survival stress activated protein kinases and DNA repair networks. Many of the changes seen at the proteomics level were confirmed at the gene level using microarray expression data. This suggests an enhanced level of basal repair mechanisms in HLNRA individuals. The scientific program at BARC thus, focuses on fundamental scientific understanding of the mechanisms cells use to sense, repair and adapt to low dose radiation. Implications of these cellular processes for low dose radiation risk estimation will be discussed. (author)

Effects of high vs low-level radiation exposure

International Nuclear Information System (INIS)

Bond, V.P.

1983-01-01

In order to appreciate adequately the various possible effects of radiation, particularly from high-level vs low-level radiation exposure (HLRE, vs LLRE), it is necessary to understand the substantial differences between (a) exposure as used in exposure-incidence curves, which are always initially linear and without threshold, and (b) dose as used in dose-response curves, which always have a threshold, above which the function is curvilinear with increasing slope. The differences are discussed first in terms of generally familiar nonradiation situations involving dose vs exposure, and then specifically in terms of exposure to radiation, vs a dose of radiation. Examples are given of relevant biomedical findings illustrating that, while dose can be used with HLRE, it is inappropriate and misleading the LLRE where exposure is the conceptually correct measure of the amount of radiation involved

Human exposure assessment to environmental chemicals using biomonitoring.

Science.gov (United States)

Calafat, Antonia M; Ye, Xiaoyun; Silva, Manori J; Kuklenyik, Zsuzsanna; Needham, Larry L

2006-02-01

In modern societies, humans may be exposed to a wide spectrum of environmental chemicals. Although the health significance of this exposure for many chemicals is unknown, studies to investigate the prevalence of exposure are warranted because of the chemicals' potential harmful health effects, as often indicated in animal studies. Three tools have been used to assess exposure: exposure history/questionnaire information, environmental monitoring, and biomonitoring (i.e. measuring concentrations of the chemicals, their metabolites, or their adducts in human specimens). We present an overview on the use of biomonitoring in exposure assessment using phthalates, bisphenol A and other environmental phenols, and perfluorinated chemicals as examples. We discuss some factors relevant for interpreting and understanding biomonitoring data, including selection of both biomarkers of exposure and human matrices, and toxicokinetic information. The use of biomonitoring in human risk assessment is not discussed.

The implications of ICRP publication (60) 1990 for public exposure to natural radiation

International Nuclear Information System (INIS)

Laughlin, J.Mc.

1992-01-01

The implications of the new ICRP recommendations on the control of public exposure to natural radiation are described. As ICRP differentiates between Practices and Interventions the application of the basic recommendations in the case of natural radiation exposures will be discussed in this context. Particular emphasis will be placed on public exposure to indoor radon with some discussion on situations in which occupational and public exposure to this source occur together. This major source of public exposure i discussed in relation to both ICRP 60 and ICRP 39. Some of the difficulties that the new recommendations may give rise to in the management of natural radiation exposures are discussed. One of the major changes in the new recommendations concerns the area of risk. This will be briefly discussed as regards the ways in which the risk arising from public exposure to natural radiation may be assessed. (author)

Biomarkers of acute respiratory allergen exposure: Screening for sensitization potential

International Nuclear Information System (INIS)

Pucheu-Haston, Cherie M.; Copeland, Lisa B.; Vallanat, Beena; Boykin, Elizabeth; Ward, Marsha D.W.

2010-01-01

Effective hazard screening will require the development of high-throughput or in vitro assays for the identification of potential sensitizers. The goal of this preliminary study was to identify potential biomarkers that differentiate the response to allergens vs non-allergens following an acute exposure in naive individuals. Female BALB/c mice received a single intratracheal aspiration exposure to Metarhizium anisopliae crude antigen (MACA) or bovine serum albumin (BSA) in Hank's Balanced Salt Solution (HBSS) or HBSS alone. Mice were terminated after 1, 3, 6, 12, 18 and 24 h. Bronchoalveolar lavage fluid (BALF) was evaluated to determine total and differential cellularity, total protein concentration and LDH activity. RNA was isolated from lung tissue for microarray analysis and qRT-PCR. MACA administration induced a rapid increase in BALF neutrophils, lymphocytes, eosinophils and total protein compared to BSA or HBSS. Microarray analysis demonstrated differential expression of genes involved in cytokine production, signaling, inflammatory cell recruitment, adhesion and activation in 3 and 12 h MACA-treated samples compared to BSA or HBSS. Further analyses allowed identification of ∼ 100 candidate biomarker genes. Eleven genes were selected for further assessment by qRT-PCR. Of these, 6 demonstrated persistently increased expression (Ccl17, Ccl22, Ccl7, Cxcl10, Cxcl2, Saa1), while C3ar1 increased from 6-24 h. In conclusion, a single respiratory exposure of mice to an allergenic mold extract induces an inflammatory response which is distinct in phenotype and gene transcription from the response to a control protein. Further validation of these biomarkers with additional allergens and irritants is needed. These biomarkers may facilitate improvements in screening methods.

Chronic wasting disease prion infection of differentiated neurospheres.

Science.gov (United States)

Iwamaru, Yoshifumi; Mathiason, Candace K; Telling, Glenn C; Hoover, Edward A

2017-07-04

A possible strategy to develop more diverse cell culture systems permissive to infection with naturally occurring prions is to exploit culture of neurospheres from transgenic mice expressing the normal prion protein (PrP) of the native host species. Accordingly, we developed differentiated neurosphere cultures from the cervid PrP-expressing mice to investigate whether this in vitro system would support replication of non-adapted cervid-origin chronic wasting disease (CWD) prions. Here we report the successful amplification of disease-associated PrP in differentiated neurosphere cultures within 3 weeks after exposure to CWD prions from both white-tailed deer or elk. This neurosphere culture system provides a new in vitro tool that can be used to assess non-adapted CWD prion propagation and transmission.

The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells

International Nuclear Information System (INIS)

Li, Xiao-Fei; Wu, Xiao-Rong; Xue, Ming; Wang, Yan; Wang, Jie; Li, Yang; Suriguga,; Zhang, Guang-Yao; Yi, Zong-Chun

2012-01-01

Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, β-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, β-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes. -- Highlights: ► Catechol enhanced hemin-induced hemoglobin accumulation. ► Exposure to catechol resulted in up-regulated expression of erythroid genes. ► Catechol reduced methylation levels at some CpG sites in erythroid genes.

The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells

Energy Technology Data Exchange (ETDEWEB)

Li, Xiao-Fei; Wu, Xiao-Rong; Xue, Ming; Wang, Yan; Wang, Jie; Li, Yang; Suriguga,; Zhang, Guang-Yao; Yi, Zong-Chun, E-mail: yizc@buaa.edu.cn

2012-11-15

Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, β-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, β-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes. -- Highlights: ► Catechol enhanced hemin-induced hemoglobin accumulation. ► Exposure to catechol resulted in up-regulated expression of erythroid genes. ► Catechol reduced methylation levels at some CpG sites in erythroid genes.

Non-differential underestimation may cause a threshold effect of exposure to appear as a dose-response relationship

NARCIS (Netherlands)

Verkerk, P. H.; Buitendijk, S. E.

1992-01-01

It is generally believed that non-differential misclassification will lead to a bias toward the null-value. However, using one graphical and one numerical example, we show that in situations where underestimation more than overestimation is the problem, non-differential misclassification may lead to

How can GPS technology help us better understand exposure to the food environment? A systematic review.

Science.gov (United States)

Cetateanu, Andreea; Jones, Andy

2016-12-01

Global Positioning Systems (GPS) are increasingly being used to objectively assess movement patterns of people related to health behaviours. However research detailing their application to the food environment is scarce. This systematic review examines the application of GPS in studies of exposure to food environments and their potential influences on health. Based on an initial scoping exercise, published articles to be included in the systematic review were identified from four electronic databases and reference lists and were appraised and analysed, the final cut-off date for inclusion being January 2015. Included studies used GPS to identify location of individuals in relation to food outlets and link that to health or diet outcomes. They were appraised against a set of quality criteria. Six studies met the inclusion criteria, which were appraised to be of moderate quality. Newer studies had a higher quality score. Associations between observed mobility patterns in the food environment and diet related outcomes were equivocal. Findings agreed that traditional food exposure measures overestimate the importance of the home food environment. The use of GPS to measure exposure to the food environment is still in its infancy yet holds much potential. There are considerable variations and challenges in developing and standardising the methods used to assess exposure.

The Pregnancy Exposome: Multiple Environmental Exposures in the INMA-Sabadell Birth Cohort.

Science.gov (United States)

Robinson, Oliver; Basagaña, Xavier; Agier, Lydiane; de Castro, Montserrat; Hernandez-Ferrer, Carles; Gonzalez, Juan R; Grimalt, Joan O; Nieuwenhuijsen, Mark; Sunyer, Jordi; Slama, Rémy; Vrijheid, Martine

2015-09-01

The "exposome" is defined as "the totality of human environmental exposures from conception onward, complementing the genome" and its holistic approach may advance understanding of disease etiology. We aimed to describe the correlation structure of the exposome during pregnancy to better understand the relationships between and within families of exposure and to develop analytical tools appropriate to exposome data. Estimates on 81 environmental exposures of current health concern were obtained for 728 women enrolled in The INMA (INfancia y Medio Ambiente) birth cohort, in Sabadell, Spain, using biomonitoring, geospatial modeling, remote sensors, and questionnaires. Pair-wise Pearson's and polychoric correlations were calculated and principal components were derived. The median absolute correlation across all exposures was 0.06 (5th-95th centiles, 0.01-0.54). There were strong levels of correlation within families of exposure (median = 0.45, 5th-95th centiles, 0.07-0.85). Nine exposures (11%) had a correlation higher than 0.5 with at least one exposure outside their exposure family. Effectively all the variance in the data set (99.5%) was explained by 40 principal components. Future exposome studies should interpret exposure effects in light of their correlations to other exposures. The weak to moderate correlation observed between exposure families will permit adjustment for confounding in future exposome studies.

Exposure Based Health Issues Project Report: Phase I of High Level Tank Operations, Retrieval, Pretreatment, and Vitrification Exposure Based Health Issues Analysis

International Nuclear Information System (INIS)

Stenner, Robert D.; Bowers, Harold N.; Kenoyer, Judson L.; Strenge, Dennis L.; Brady, William H.; Ladue, Buffi; Samuels, Joseph K.

2001-01-01

The Department of Energy (DOE) has the responsibility to understand the ''big picture'' of worker health and safety which includes fully recognizing the vulnerabilities and associated programs necessary to protect workers at the various DOE sites across the complex. Exposure analysis and medical surveillance are key aspects for understanding this big picture, as is understanding current health and safety practices and how they may need to change to relate to future health and safety management needs. The exposure-based health issues project was initiated to assemble the components necessary to understand potential exposure situations and their medical surveillance and clinical aspects. Phase I focused only on current Hanford tank farm operations and serves as a starting point for the overall project. It is also anticipated that once the pilot is fully developed for Hanford HLW (i.e., current operations, retrieval, pretreatment, vitrification, and disposal), the process and analysis methods developed will be available and applicable for other DOE operations and sites. The purpose of this Phase I project report is to present the health impact information collected regarding ongoing tank waste maintenance operations, show the various aspects of health and safety involved in protecting workers, introduce the reader to the kinds of information that will need to be analyzed in order to effectively manage worker safety

Preschool outcomes following prenatal serotonin reuptake inhibitor exposure: differences in language and behavior, but not cognitive function.

Science.gov (United States)

Johnson, Katrina C; Smith, Alicia K; Stowe, Zachary N; Newport, D Jeffrey; Brennan, Patricia A

2016-02-01

To test the hypothesis that prenatal exposure to serotonin reuptake inhibitors (SRIs) is associated with language and behavioral outcomes in preschool-aged children, while accounting for confounds such as concomitant exposures and maternal mental illness. An observational, prospective, longitudinal study of mental illness in pregnancy was conducted at a university-based women's mental health clinic (April 2010-November 2012). A sample of 178 mother-child dyads participated in a laboratory visit at preschool age (2.5-5.5 years). The majority of women (87%) received psychotropic medication during pregnancy. Psychiatric status (based on DSM-IV), other medication use, and substance use were serially assessed and tested as confounds. Primary outcome measures included standardized measures of expressive language and cognitive function and mother and alternate caregiver ratings of child behavior problems, including the Pervasive Developmental Disorders (PDD) subscale of the Child Behavior Checklist. Linear regression analyses revealed that, after controlling for relevant covariates, expressive language scores from the Test of Early Language Development, 3rd edition, were negatively associated with prenatal SRI exposure (β = -0.15, t = -2.41), while the PDD behavioral problems subscales completed by alternate caregivers and mothers were positively associated with prenatal SRI exposure (β = 0.17, t = 2.01; β = 0.16, t = 2.00, respectively). Cognitive function, measured using the Differential Ability Scales, 2nd edition, was not associated with any medication exposures. The current data suggest a small but significant association between prenatal SRI exposure and preschool outcomes, including expressive language and behavior problems. These data corroborate data from recent, population-based studies, although overall, published findings are mixed. Replication and identification of moderating risk factors are needed to understand potential clinical implications. �

HESI pilot project: Testing a qualitative approach for incorporating exposure into alternatives assessment

DEFF Research Database (Denmark)

Greggs, Bill; Arnold, Scott; Burns, Thomas J.

-quantitative exposure assessment on the alternatives being considered. This talk will demonstrate an approach for including chemical and product exposure information in a qualitative AA comparison. Starting from existing hazard AAs, a series of four exposure examples were examined to test the concept, to understand...

Diclofenac and triamcinolone acetonide impair tenocytic differentiation and promote adipocytic differentiation of mesenchymal stem cells

OpenAIRE

Fredriksson, Maritha; Li, Yan; St?lman, Anders; Haldos?n, Lars-Arne; Fell?nder-Tsai, Li

2013-01-01

Background Tendinopathies are often empirically treated with oral/topical nonsteroidal anti-inflammatory medications and corticosteroid injections despite their unclear effects on tendon regeneration. Recent studies indicate that tendon progenitors exhibit stem cell-like properties, i.e., differentiation to osteoblasts, adipocytes, and chondrocytes, in addition to tenocytes. Our present study aims at understanding the effects of triamcinolone acetonide and diclofenac on tenocytic differentiat...

Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

KAUST Repository

Mu, Huawei; Sun, Jin; Cheung, Siu Gin; Fang, Ling; Zhou, Haiyun; Luan, Tiangang; Zhang, Huoming; Wong, Chris K.C.; Qiu, Jian-Wen

2017-01-01

Although high-throughput proteomics has been widely applied to study mechanisms of environmental adaptation, the conclusions from studies that are based on one species can be confounded by phylogeny. We compare the freshwater snail Pomacea canaliculata (a notorious invasive species) and its congener Pomacea diffusa (a non-invasive species) to understand the molecular mechanisms of their differential resistance to hypoxia. A 72-h acute exposure experiment showed that P. canaliculata is more tolerant to hypoxia than P. diffusa. The two species were then exposed to three levels of dissolved oxygen (6.7, 2.0 and 1.0mgL−1) for 8h, and their gill proteins were analyzed using iTRAQ-coupled LC-MS/MS. The two species showed striking differences in protein expression profiles, with the more hypoxia tolerant P. canaliculata having more up-regulated proteins in signal transduction and down-regulated proteins in glycolysis and the tricarboxylic acid cycle. Evolutionary analysis revealed five orthologous genes encoding differentially expressed proteins having clear signal of positive selection, indicating selection has acted on some of the hypoxia responsive genes. Our case study has highlighted the potential of integrated proteomics and comparative evolutionary analysis for understanding the genetic basis of adaptation to global environmental change in non-model species. SignificanceRapid globalization in recent decades has greatly facilitated species introduction around the world. Successfully established introduced species, so-called invasive species, have threatened the invaded ecosystems. There has been substantial interest in studying how invasive species respond to extreme environmental conditions because the results can help not only predict their range of expansion and manage their impact, but also may reveal the adaptive mechanisms underlying their invasiveness. Our study has adopted a comparative approach to study the differential physiological and proteomic

Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

KAUST Repository

Mu, Huawei

2017-11-06

Although high-throughput proteomics has been widely applied to study mechanisms of environmental adaptation, the conclusions from studies that are based on one species can be confounded by phylogeny. We compare the freshwater snail Pomacea canaliculata (a notorious invasive species) and its congener Pomacea diffusa (a non-invasive species) to understand the molecular mechanisms of their differential resistance to hypoxia. A 72-h acute exposure experiment showed that P. canaliculata is more tolerant to hypoxia than P. diffusa. The two species were then exposed to three levels of dissolved oxygen (6.7, 2.0 and 1.0mgL−1) for 8h, and their gill proteins were analyzed using iTRAQ-coupled LC-MS/MS. The two species showed striking differences in protein expression profiles, with the more hypoxia tolerant P. canaliculata having more up-regulated proteins in signal transduction and down-regulated proteins in glycolysis and the tricarboxylic acid cycle. Evolutionary analysis revealed five orthologous genes encoding differentially expressed proteins having clear signal of positive selection, indicating selection has acted on some of the hypoxia responsive genes. Our case study has highlighted the potential of integrated proteomics and comparative evolutionary analysis for understanding the genetic basis of adaptation to global environmental change in non-model species. SignificanceRapid globalization in recent decades has greatly facilitated species introduction around the world. Successfully established introduced species, so-called invasive species, have threatened the invaded ecosystems. There has been substantial interest in studying how invasive species respond to extreme environmental conditions because the results can help not only predict their range of expansion and manage their impact, but also may reveal the adaptive mechanisms underlying their invasiveness. Our study has adopted a comparative approach to study the differential physiological and proteomic

A re-examination of the mere exposure effect: The influence of repeated exposure on recognition, familiarity, and liking.

Science.gov (United States)

Montoya, R Matthew; Horton, Robert S; Vevea, Jack L; Citkowicz, Martyna; Lauber, Elissa A

2017-05-01

To evaluate the veracity of models of the mere exposure effect and to understand the processes that moderate the effect, we conducted a meta-analysis of the influence of repeated exposure on liking, familiarity, recognition, among other evaluations. We estimated parameters from 268 curve estimates drawn from 81 articles and revealed that the mere exposure effect was characterized by a positive slope and negative quadratic effect consistent with an inverted-U shaped curve. In fact, such curves were associated with (a) all visual, but not auditory stimuli; (b) exposure durations shorter than 10 s and longer than 1 min; (c) both homogeneous and heterogeneous presentation types; and (d) ratings that were taken after all stimuli were presented. We conclude that existing models for the mere exposure effect do not adequately account for the findings, and we provide a framework to help guide future research. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Effects of Substrate and Co-Culture on Neural Progenitor Cell Differentiation

Energy Technology Data Exchange (ETDEWEB)

Jones, Erin Boote [Iowa State Univ., Ames, IA (United States)

2008-01-01

In recent years the study of stem and progenitor cells has moved to the forefront of research. Since the isolation of human hematopoietic stem cells in 1988 and the subsequent discovery of a self renewing population of multipotent cells in many tissues, many researchers have envisioned a better understanding of development and potential clinical usage in intractable diseases. Both these goals, however, depend on a solid understanding of the intracellular and extracellular forces that cause stem cells to differentiate to a specific cell fate. Many diseases of large scale cell loss have been suggested as candidates for stem cell based treatments. It is proposed that replacing the function of the damaged or defective cells by specific differentiation of stem or progenitor cells could treat the disease. Before cells can be directed to specific lineages, the mechanisms of differentiation must be better understood. Differentiation in vivo is an intensively complex system that is difficult to study. The goal of this research is to develop further understanding of the effects of soluble and extracellular matrix (ECM) cues on the differentiation of neural progenitor cells with the use of a simplified in vitro culture system. Specific research objectives are to study the differentiation of neural progenitor cells in response to astrocyte conditioned medium and protein substrate composition and concentration. In an effort to reveal the mechanism of the conditioned medium interaction, a test for the presence of a feedback loop between progenitor cells and astrocytes is presented along with an examination of conditioned medium storage temperature, which can reveal enzymatic dependencies. An examination of protein substrate composition and concentration will help to reveal the role of any ECM interactions on differentiation. This thesis is organized into a literature review covering recent advances in use of external modulators of differentiation such as surface coatings, co

Current understanding of the toxicological risk posed to the fetus following maternal exposure to nanoparticles.

Science.gov (United States)

Zhang, Yanli; Wu, Junrong; Feng, Xiaoli; Wang, Ruolan; Chen, Aijie; Shao, Longquan

2017-12-01

With the broad use of nanotechnology, the number and variety of nanoparticles that humans can be exposed to has further increased. Consequently, there is growing concern about the potential effect of maternal exposure to various nanoparticles during pregnancy on a fetus. However, the nature of this risk is not fully known. Areas covered: In this review, materno-fetal transfer of nanoparticles through the placenta is described. Both prenatal and postnatal adverse effects, such as fetal resorption, malformation and injury to various organs in mice exposed to nanoparticles are reviewed. The potential mechanisms of toxicity are also discussed. Expert opinion: The toxicology and safe application of recently developed nanoparticles has attracted much attention in the past few years. Although many studies have demonstrated the toxicology of nanoparticles in various species, only a small number of studies have examined the effect on a fetus after maternal exposure to nanoparticles. This is particularly important, because the developing fetus is especially vulnerable to the toxic effects of nanoparticles during fetal development due to the unique physical stage of the fetus. Nanoparticles may directly or indirectly impair fetal development and growth after maternal exposure to nanoparticles.

Changes in health perceptions after exposure to human suffering: using discrete emotions to understand underlying processes.

Directory of Open Access Journals (Sweden)

Antonia A Paschali

Full Text Available BACKGROUND: The aim of this study was to examine whether exposure to human suffering is associated with negative changes in perceptions about personal health. We further examined the relation of possible health perception changes, to changes in five discrete emotions (i.e., fear, guilt, hostility/anger, and joviality, as a guide to understand the processes underlying health perception changes, provided that each emotion conveys information regarding triggering conditions. METHODOLOGY/FINDINGS: An experimental group (N = 47 was exposed to images of human affliction, whereas a control group (N = 47 was exposed to relaxing images. Participants in the experimental group reported more health anxiety and health value, as well as lower health-related optimism and internal health locus of control, in comparison to participants exposed to relaxing images. They also reported more fear, guilt, hostility and sadness, as well as less joviality. Changes in each health perception were related to changes in particular emotions. CONCLUSION: These findings imply that health perceptions are shaped in a constant dialogue with the representations about the broader world. Furthermore, it seems that the core of health perception changes lies in the acceptance that personal well-being is subject to several potential threats, as well as that people cannot fully control many of the factors the determine their own well-being.

Differential effect of waterborne cadmium exposure on lipid metabolism in liver and muscle of yellow catfish Pelteobagrus fulvidraco

International Nuclear Information System (INIS)

Chen, Qi-Liang; Gong, Yuan; Luo, Zhi; Zheng, Jia-Lang; Zhu, Qing-Ling

2013-01-01

Highlights: •Cd triggered hepatic lipid accumulation through the improvement of lipogenesis. •Lipid homeostasis in muscle after Cd exposure derived from the down-regulation of both lipogenesis and lipolysis. •Our study determines the mechanism of waterborne Cd exposure on lipid metabolism in fish on a molecular level. •Our study indicates the tissue-specific regulatory effect of lipid metabolism under waterborne Cd exposure. -- Abstract: The present study was conducted to investigate the effect of waterborne cadmium (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and 0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation, the activities and expression level of several enzymes as well as the mRNA expression of transcription factors involved in lipid metabolism in liver and muscle were determined. Waterborne Cd exposure reduced growth performance, but increased Cd accumulation in liver and muscle. In liver, lipid content, the activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome proliferators-activated receptor (PPAR) α were down-regulated by Cd exposure. Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions of CPT1 and PPARγ showed no significant differences among the treatments. In muscle, lipid contents showed no significant differences among the treatments. The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARα and PPARγ were down-regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic lipid accumulation through the improvement of lipogenesis, and that lipid homeostasis in muscle was probably conducted by the down

Differential effect of waterborne cadmium exposure on lipid metabolism in liver and muscle of yellow catfish Pelteobagrus fulvidraco

Energy Technology Data Exchange (ETDEWEB)

Chen, Qi-Liang; Gong, Yuan [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China); Luo, Zhi, E-mail: luozhi99@mail.hzau.edu.cn [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China); Zheng, Jia-Lang; Zhu, Qing-Ling [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China)

2013-10-15

Highlights: •Cd triggered hepatic lipid accumulation through the improvement of lipogenesis. •Lipid homeostasis in muscle after Cd exposure derived from the down-regulation of both lipogenesis and lipolysis. •Our study determines the mechanism of waterborne Cd exposure on lipid metabolism in fish on a molecular level. •Our study indicates the tissue-specific regulatory effect of lipid metabolism under waterborne Cd exposure. -- Abstract: The present study was conducted to investigate the effect of waterborne cadmium (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and 0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation, the activities and expression level of several enzymes as well as the mRNA expression of transcription factors involved in lipid metabolism in liver and muscle were determined. Waterborne Cd exposure reduced growth performance, but increased Cd accumulation in liver and muscle. In liver, lipid content, the activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome proliferators-activated receptor (PPAR) α were down-regulated by Cd exposure. Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions of CPT1 and PPARγ showed no significant differences among the treatments. In muscle, lipid contents showed no significant differences among the treatments. The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARα and PPARγ were down-regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic lipid accumulation through the improvement of lipogenesis, and that lipid homeostasis in muscle was probably conducted by the down

Chronic bronchiolitis in non-human primates after prolonged ozone exposure

International Nuclear Information System (INIS)

Eustis, S.L.

1979-01-01

Bonnet monkeys (Macaca radiata) were exposed to 0.0, 0.5, and 0.8 ppM ozone for 7, 28, or 90 consecutive d, eight h per d. Changes in the lung evoked by prolonged oxidant exposure were evaluated by light microscopy, scanning electron microscopy, transmission electron microscopy, autoradiography, and morphometry. Morphological changes were principally characterized as a low-grade chronic respiratory bronchiolitis. Proximal generations of respiratory bronchioles were the most consistently affected region of the pulmonary acinus. Major features of the bronchiolitis were intraluminal accumulations of macrophages and hypertrophy and hyperplasia of cuboidal bronchiolar epithelial cells. The degree of inflammation was greatest at the 0.8 ppM ozone concentration at each exposure period. The number of inflammatory cells observed at 90 d, however, was about one-half that observed at 7 d. Tritiated thymidine labeling and differential cell counts of respiratory bronchiolar epithelium demonstrated a proliferative response and an increase in the proportion of cubiodal bronchiolar cells which presumably function as the progenitor cell during cell renewal and repair of the epithelium. The labeling index remained elevated above control values through 90 d of ozone exposure despite a reduction below 7 d values at both 28 and 90 d. The epithelial hyperplasia persisted through 90 d at a level similar to but slightly above that present at 7 d. Since cell differentials remained shifted at 28 and 90 d, it appears that persistent ozone exposure delayed maturation and transformation of cubiodal bronchiolar cells to their mature phenotype

Understanding of Self and Maternal Warmth Predict Later Self-Regulation in Toddlers

Science.gov (United States)

Jennings, Kay D.; Sandberg, Ian; Kelley, Sue A.; Valdes, Lourdes; Yaggi, Kirsten; Abrew, Amy; Macey-Kalcevic, Melody

2008-01-01

Research on the development of self-regulation has focused primarily on the roles of maternal behavior and attention, but cognitive understanding of the self is also likely to contribute, as is exposure to maternal depression. In this study toddlers' understanding of self-as-object and understanding of agency were assessed behaviorally at both 20…

The use of environmental metabolomics to determine glyphosate level of exposure in rapeseed (Brassica napus L.) seedlings

International Nuclear Information System (INIS)

Petersen, Iben Lykke; Tomasi, Giorgio; Sorensen, Hilmer; Boll, Esther S.; Hansen, Hans Christian Bruun; Christensen, Jan H.

2011-01-01

Metabolic profiling in plants can be used to differentiate between treatments and to search for biomarkers for exposure. A methodology for processing Ultra-High-Performance Liquid Chromatography-Diode-Array-Detection data is devised. This methodology includes a scheme for selecting informative wavelengths, baseline removal, retention time alignment, selection of relevant retention times, and principal component analysis (PCA). Plant crude extracts from rapeseed seedling exposed to sublethal concentrations of glyphosate are used as a study case. Through this approach, plants exposed to concentrations down to 5 μM could be distinguished from the controls. The compounds responsible for this differentiation were partially identified and were different from those specific for high exposure samples, which suggests that two different responses to glyphosate are elicited in rapeseed depending on the level of exposure. The PCA loadings indicate that a combination of other metabolites could be more sensitive than the response of shikimate to detect glyphosate exposure. - Highlights: → A method for processing UHPLC-DAD data for plant metabolic profiling is devised. → The metabolic profiling approach is more sensitive to glyphosate exposure than shikimate. → Plants exposed to concentrations down to 5 μM can be distinguished from the controls. → Two different responses to glyphosate may be elicited in rapeseed depending on the level of exposure. - A novel untargeted environmental metabololomic approach is used to detect low-level glyphosate exposure of rapeseed seedlings.

The use of environmental metabolomics to determine glyphosate level of exposure in rapeseed (Brassica napus L.) seedlings

Energy Technology Data Exchange (ETDEWEB)

Petersen, Iben Lykke; Tomasi, Giorgio; Sorensen, Hilmer; Boll, Esther S.; Hansen, Hans Christian Bruun [Department of Basic Sciences and Environment, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg C (Denmark); Christensen, Jan H., E-mail: jch@life.ku.dk [Department of Basic Sciences and Environment, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg C (Denmark)

2011-10-15

Metabolic profiling in plants can be used to differentiate between treatments and to search for biomarkers for exposure. A methodology for processing Ultra-High-Performance Liquid Chromatography-Diode-Array-Detection data is devised. This methodology includes a scheme for selecting informative wavelengths, baseline removal, retention time alignment, selection of relevant retention times, and principal component analysis (PCA). Plant crude extracts from rapeseed seedling exposed to sublethal concentrations of glyphosate are used as a study case. Through this approach, plants exposed to concentrations down to 5 {mu}M could be distinguished from the controls. The compounds responsible for this differentiation were partially identified and were different from those specific for high exposure samples, which suggests that two different responses to glyphosate are elicited in rapeseed depending on the level of exposure. The PCA loadings indicate that a combination of other metabolites could be more sensitive than the response of shikimate to detect glyphosate exposure. - Highlights: > A method for processing UHPLC-DAD data for plant metabolic profiling is devised. > The metabolic profiling approach is more sensitive to glyphosate exposure than shikimate. > Plants exposed to concentrations down to 5 {mu}M can be distinguished from the controls. > Two different responses to glyphosate may be elicited in rapeseed depending on the level of exposure. - A novel untargeted environmental metabololomic approach is used to detect low-level glyphosate exposure of rapeseed seedlings.

Partial Differential Equations Modeling and Numerical Simulation

CERN Document Server

Glowinski, Roland

2008-01-01

This book is dedicated to Olivier Pironneau. For more than 250 years partial differential equations have been clearly the most important tool available to mankind in order to understand a large variety of phenomena, natural at first and then those originating from human activity and technological development. Mechanics, physics and their engineering applications were the first to benefit from the impact of partial differential equations on modeling and design, but a little less than a century ago the Schrödinger equation was the key opening the door to the application of partial differential equations to quantum chemistry, for small atomic and molecular systems at first, but then for systems of fast growing complexity. Mathematical modeling methods based on partial differential equations form an important part of contemporary science and are widely used in engineering and scientific applications. In this book several experts in this field present their latest results and discuss trends in the numerical analy...

The Screening of Genes Sensitive to Long-Term, Low-Level Microwave Exposure and Bioinformatic Analysis of Potential Correlations to Learning and Memory.

Science.gov (United States)

Zhao, Ya Li; Li, Ying Xian; Ma, Hong Bo; Li, Dong; Li, Hai Liang; Jiang, Rui; Kan, Guang Han; Yang, Zhen Zhong; Huang, Zeng Xin

2015-08-01

To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction. Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR. The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memorye. Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Chromatin remodeling agent trichostatin A: a key-factor in the hepatic differentiation of human mesenchymal stem cells derived of adult bone marrow

Directory of Open Access Journals (Sweden)

Vinken Mathieu

2007-04-01

Full Text Available Abstract Background The capability of human mesenchymal stem cells (hMSC derived of adult bone marrow to undergo in vitro hepatic differentiation was investigated. Results Exposure of hMSC to a cocktail of hepatogenic factors [(fibroblast growth factor-4 (FGF-4, hepatocyte growth factor (HGF, insulin-transferrin-sodium-selenite (ITS and dexamethasone] failed to induce hepatic differentiation. Sequential exposure to these factors (FGF-4, followed by HGF, followed by HGF+ITS+dexamethasone, however, resembling the order of secretion during liver embryogenesis, induced both glycogen-storage and cytokeratin (CK18 expression. Additional exposure of the cells to trichostatin A (TSA considerably improved endodermal differentiation, as evidenced by acquisition of an epithelial morphology, chronological expression of hepatic proteins, including hepatocyte-nuclear factor (HNF-3β, alpha-fetoprotein (AFP, CK18, albumin (ALB, HNF1α, multidrug resistance-associated protein (MRP2 and CCAAT-enhancer binding protein (C/EBPα, and functional maturation, i.e. upregulated ALB secretion, urea production and inducible cytochrome P450 (CYP-dependent activity. Conclusion hMSC are able to undergo mesenchymal-to-epithelial transition. TSA is hereby essential to promote differentiation of hMSC towards functional hepatocyte-like cells.

Exposure of highway maintenance workers to fine particulate matter and noise

Science.gov (United States)

In this study we assessed the mixed exposure of highway maintenance workers to airborne particles, noise and gaseous co-pollutants. The aims were to provide a better understanding of the workers exposure to facilitate the evaluation of short-term effects on cardiovascular health ...

Estimating Inorganic Arsenic Exposure from U.S. Rice and Total Water Intakes

OpenAIRE

Mantha, Madhavi; Yeary, Edward; Trent, John; Creed, Patricia A.; Kubachka, Kevin; Hanley, Traci; Shockey, Nohora; Heitkemper, Douglas; Caruso, Joseph; Xue, Jianping; Rice, Glenn; Wymer, Larry; Creed, John T.

2017-01-01

Background: Among nonoccupationally exposed U.S. residents, drinking water and diet are considered primary exposure pathways for inorganic arsenic (iAs). In drinking water, iAs is the primary form of arsenic (As), while dietary As speciation techniques are used to differentiate iAs from less toxic arsenicals in food matrices. Objectives: Our goal was to estimate the distribution of iAs exposure rates from drinking water intakes and rice consumption in the U.S. population and ethnic- and age-b...

Understanding gene expression in coronary artery disease through ...

Indian Academy of Sciences (India)

Understanding gene expression in coronary artery disease through global profiling, network analysis and independent validation of key candidate genes. Prathima ... Table 2. Differentially expressed genes in CAD compared to age and gender matched controls. .... Regulation of nuclear pre-mRNA domain containing 1A.

Comparison of modeling approaches to prioritize chemicals based on estimates of exposure and exposure potential.

Science.gov (United States)

Mitchell, Jade; Arnot, Jon A; Jolliet, Olivier; Georgopoulos, Panos G; Isukapalli, Sastry; Dasgupta, Surajit; Pandian, Muhilan; Wambaugh, John; Egeghy, Peter; Cohen Hubal, Elaine A; Vallero, Daniel A

2013-08-01

While only limited data are available to characterize the potential toxicity of over 8 million commercially available chemical substances, there is even less information available on the exposure and use-scenarios that are required to link potential toxicity to human and ecological health outcomes. Recent improvements and advances such as high throughput data gathering, high performance computational capabilities, and predictive chemical inherency methodology make this an opportune time to develop an exposure-based prioritization approach that can systematically utilize and link the asymmetrical bodies of knowledge for hazard and exposure. In response to the US EPA's need to develop novel approaches and tools for rapidly prioritizing chemicals, a "Challenge" was issued to several exposure model developers to aid the understanding of current systems in a broader sense and to assist the US EPA's effort to develop an approach comparable to other international efforts. A common set of chemicals were prioritized under each current approach. The results are presented herein along with a comparative analysis of the rankings of the chemicals based on metrics of exposure potential or actual exposure estimates. The analysis illustrates the similarities and differences across the domains of information incorporated in each modeling approach. The overall findings indicate a need to reconcile exposures from diffuse, indirect sources (far-field) with exposures from directly, applied chemicals in consumer products or resulting from the presence of a chemical in a microenvironment like a home or vehicle. Additionally, the exposure scenario, including the mode of entry into the environment (i.e. through air, water or sediment) appears to be an important determinant of the level of agreement between modeling approaches. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison of modeling approaches to prioritize chemicals based on estimates of exposure and exposure potential

Science.gov (United States)

Mitchell, Jade; Arnot, Jon A.; Jolliet, Olivier; Georgopoulos, Panos G.; Isukapalli, Sastry; Dasgupta, Surajit; Pandian, Muhilan; Wambaugh, John; Egeghy, Peter; Cohen Hubal, Elaine A.; Vallero, Daniel A.

2014-01-01

While only limited data are available to characterize the potential toxicity of over 8 million commercially available chemical substances, there is even less information available on the exposure and use-scenarios that are required to link potential toxicity to human and ecological health outcomes. Recent improvements and advances such as high throughput data gathering, high performance computational capabilities, and predictive chemical inherency methodology make this an opportune time to develop an exposure-based prioritization approach that can systematically utilize and link the asymmetrical bodies of knowledge for hazard and exposure. In response to the US EPA’s need to develop novel approaches and tools for rapidly prioritizing chemicals, a “Challenge” was issued to several exposure model developers to aid the understanding of current systems in a broader sense and to assist the US EPA’s effort to develop an approach comparable to other international efforts. A common set of chemicals were prioritized under each current approach. The results are presented herein along with a comparative analysis of the rankings of the chemicals based on metrics of exposure potential or actual exposure estimates. The analysis illustrates the similarities and differences across the domains of information incorporated in each modeling approach. The overall findings indicate a need to reconcile exposures from diffuse, indirect sources (far-field) with exposures from directly, applied chemicals in consumer products or resulting from the presence of a chemical in a microenvironment like a home or vehicle. Additionally, the exposure scenario, including the mode of entry into the environment (i.e. through air, water or sediment) appears to be an important determinant of the level of agreement between modeling approaches. PMID:23707726

Redefining the expression and function of the inhibitor of differentiation 1 in mammary gland development.

Directory of Open Access Journals (Sweden)

Radhika Nair

2010-08-01

Full Text Available The accumulation of poorly differentiated cells is a hallmark of breast neoplasia and progression. Thus an understanding of the factors controlling mammary differentiation is critical to a proper understanding of breast tumourigenesis. The Inhibitor of Differentiation 1 (Id1 protein has well documented roles in the control of mammary epithelial differentiation and proliferation in vitro and breast cancer progression in vivo. However, it has not been determined whether Id1 expression is sufficient for the inhibition of mammary epithelial differentiation or the promotion of neoplastic transformation in vivo. We now show that Id1 is not commonly expressed by the luminal mammary epithelia, as previously reported. Generation and analysis of a transgenic mouse model of Id1 overexpression in the mammary gland reveals that Id1 is insufficient for neoplastic progression in virgin animals or to prevent terminal differentiation of the luminal epithelia during pregnancy and lactation. Together, these data demonstrate that there is no luminal cell-autonomous role for Id1 in mammary epithelial cell fate determination, ductal morphogenesis and terminal differentiation.

Aerosol exposure: Concepts, criteria, standards and applications

International Nuclear Information System (INIS)

Vincent, James H

2009-01-01

This paper places Inhaled Particles X in the context of the whole sequence of such symposia, going back to the first one in 1961. It draws together some of the essential principles that have been learned since that earlier meeting about the nature of exposure and exposure assessment and thus provides a framework by which to integrate the new knowledge presented at this latest one. In the process, the importance of understanding the formal definition of aerosol exposure is stressed, including the distinction between exposure intensity and exposure history, and how that relates to some measure of cumulative dose which, in turn, may be linked with knowledge about intrinsic toxicity, etc. This then leads to a definition of exposure standards, and the important ingredients of criteria, sampling and limit values. A summary is provided of the current set of particle size-selective criteria that have been widely agreed in the international occupational and environmental health community. Some ideas are presented about how this set might be expanded for certain applications, the important case of ultrafine aerosols being one of them.

Tributyltin and triphenyltin exposure promotes in vitro adipogenic differentiation but alters the adipocyte phenotype in rainbow trout.

Science.gov (United States)

Lutfi, Esmail; Riera-Heredia, Natàlia; Córdoba, Marlon; Porte, Cinta; Gutiérrez, Joaquim; Capilla, Encarnación; Navarro, Isabel

2017-07-01

Numerous environmental pollutants have been identified as potential obesogenic compounds affecting endocrine signaling and lipid homeostasis. Among them, well-known organotins such as tributyltin (TBT) and triphenyltin (TPT), can be found in significant concentrations in aquatic environments. The aim of the present study was to investigate in vitro the effects of TBT and TPT on the development and lipid metabolism of rainbow trout (Onchorynchus mykiss) primary cultured adipocytes. Results showed that TBT and TPT induced lipid accumulation and slightly enhanced peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer binding protein alpha (C/EBPα) protein expression when compared to a control, both in the presence or absence of lipid mixture. However, the effects were higher when combined with lipid, and in the absence of it, the organotins did not cause complete mature adipocyte morphology. Regarding gene expression analyses, exposure to TBT and TPT caused an increase in fatty acid synthase (fasn) mRNA levels confirming the pro-adipogenic properties of these compounds. In addition, when added together with lipid, TBT and TPT significantly increased cebpa, tumor necrosis factor alpha (tnfa) and ATP-binding cassette transporter 1 (abca1) mRNA levels suggesting a synergistic effect. Overall, our data highlighted that TBT and TPT activate adipocyte differentiation in rainbow trout supporting an obesogenic role for these compounds, although by themselves they are not able to induce complete adipocyte development and maturation suggesting that these adipocytes might not be properly functional. Copyright © 2017 Elsevier B.V. All rights reserved.

Air Pollution Exposure Modeling for Health Studies | Science ...

Science.gov (United States)

Dr. Michael Breen is leading the development of air pollution exposure models, integrated with novel personal sensor technologies, to improve exposure and risk assessments for individuals in health studies. He is co-investigator for multiple health studies assessing the exposure and effects of air pollutants. These health studies include participants with asthma, diabetes, and coronary artery disease living in various U.S. cities. He has developed, evaluated, and applied novel exposure modeling and time-activity tools, which includes the Exposure Model for Individuals (EMI), GPS-based Microenvironment Tracker (MicroTrac) and Exposure Tracker models. At this seminar, Dr. Breen will present the development and application of these models to predict individual-level personal exposures to particulate matter (PM) for two health studies in central North Carolina. These health studies examine the association between PM and adverse health outcomes for susceptible individuals. During Dr. Breen’s visit, he will also have the opportunity to establish additional collaborations with researchers at Harvard University that may benefit from the use of exposure models for cohort health studies. These research projects that link air pollution exposure with adverse health outcomes benefit EPA by developing model-predicted exposure-dose metrics for individuals in health studies to improve the understanding of exposure-response behavior of air pollutants, and to reduce participant

Differential Exposure and Reactivity to Interpersonal Stress Predict Sex Differences in Adolescent Depression

Science.gov (United States)

Shih, Josephine H.; Eberhart, Nicole K.; Hammen, Constance L.; Brennan, Patricia A.

2006-01-01

This study tested the hypothesis that higher rates of depression in adolescent girls are explained by their greater exposure and reactivity to stress in the interpersonal domain in a large sample of 15-year-olds. Findings indicate that adolescent girls experienced higher levels of total and interpersonal episodic stress, whereas boys experienced…

The 2008-2009 recession and alcohol outcomes: differential exposure and vulnerability for Black and Latino populations.

Science.gov (United States)

Zemore, Sarah E; Mulia, Nina; Jones-Webb, Rhonda J; Liu, Huiguo; Schmidt, Laura

2013-01-01

We examined whether race/ethnicity was related to exposure to acute economic losses in the 2008-2009 recession, even accounting for individual-level and geographic variables, and whether it influenced associations between economic losses and drinking patterns and problems. Data were from the 2010 National Alcohol Survey (N = 5,382). Surveys assessed both severe losses (i.e., job and housing loss) and moderate losses (i.e., reduced hours/pay and trouble paying the rent/mortgage) attributed to the 2008-2009 recession. Alcohol outcomes included total annual volume, monthly drunkenness, drinking consequences, and alcohol dependence (based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). Compared with Whites, Blacks reported significantly greater exposure to job loss and trouble paying the rent/mortgage, and Latinos reported greater exposure to all economic losses. However, only Black-White differences were robust in multivariate analyses. Interaction tests suggested that associations between exposure to economic loss and alcohol problems were stronger among Blacks than Whites. Given severe (vs. no) loss, Blacks had about 13 times the odds of both two or more drinking consequences and alcohol dependence, whereas the corresponding odds ratios for Whites were less than 3. Conversely, associations between economic loss and alcohol outcomes were weak and ambiguous among Latinos. Results suggest greater exposure to economic loss for both Blacks and Latinos (vs. Whites) and that the Black population may be particularly vulnerable to the negative effects of economic hardship on the development and/or maintenance of alcohol problems. Findings extend the economic literature and signal policy makers and service providers that Blacks and Latinos may be at special risk during economic downturns.

Exposure to Hedione Increases Reciprocity in Humans

Directory of Open Access Journals (Sweden)

Sebastian Berger

2017-05-01

Full Text Available Cooperation among unrelated humans is frequently regarded as a defining feature in the evolutionary success of our species. Whereas, much research has addressed the strategic and cognitive mechanisms that underlie cooperation, investigations into chemosensory processes have received very limited research attention. To bridge that gap, we build on recent research that has identified the chemically synthesized odorant Hedione (HED as a ligand for the putative human pheromone receptor (VN1R1 expressed in the olfactory mucosa, and hypothesize that exposure to HED may increase reciprocity. Applying behavioral economics paradigms, the present research shows that exposure to the ligand causes differentiated behavioral effects in reciprocal punishments (Study 1 as well as rewards (Study 2, two types of behaviors that are frequently regarded as essential for the development and maintenance of cooperation.

Exposure to Hedione Increases Reciprocity in Humans

Science.gov (United States)

Berger, Sebastian; Hatt, Hanns; Ockenfels, Axel

2017-01-01

Cooperation among unrelated humans is frequently regarded as a defining feature in the evolutionary success of our species. Whereas, much research has addressed the strategic and cognitive mechanisms that underlie cooperation, investigations into chemosensory processes have received very limited research attention. To bridge that gap, we build on recent research that has identified the chemically synthesized odorant Hedione (HED) as a ligand for the putative human pheromone receptor (VN1R1) expressed in the olfactory mucosa, and hypothesize that exposure to HED may increase reciprocity. Applying behavioral economics paradigms, the present research shows that exposure to the ligand causes differentiated behavioral effects in reciprocal punishments (Study 1) as well as rewards (Study 2), two types of behaviors that are frequently regarded as essential for the development and maintenance of cooperation. PMID:28512400

Basic units and concepts in radiation exposures

International Nuclear Information System (INIS)

Mlekodaj, R.L.

1992-01-01

Some of the most common units, concepts and models in use today in dealing with radiation exposures and the associated risks are presented. Discussions toward a better understanding of some of the basic difficulties in quantifying risks associated with low levels of radiation are presented. The main thrust of this talk is to lay a foundation for better understanding and appreciation of the talks to follow in this symposium

Problems associated with localised skin exposures

International Nuclear Information System (INIS)

Wells, J.

1986-01-01

The possible sources of localised skin exposure include small commercial sources (for radiotherapy, for example), radiopharmaceuticals, collimated microbeams, and both fission and activation products from nuclear reactors, neutron generators and associated facilities. Each of these sources has its own particular characteristics and associated problems. Recommendations and regulations relating to limits on skin dose for such exposures have been constrained by inadequate radiobiological data and the limitations inherent in personal dosimetric techniques. A growing body of data is now available for beta-emitters which allows a preliminary reassessment of some aspects of the currently recommended dose limits for localised skin exposures. How the skin dose is measured is particularly important for such exposures, as doses often have to be averaged over a specific area. The area chosen for dose measurement and the depth at which the measurement is made are crucial to understanding the possible biological consequences and for formulating appropriate protection criteria. (author)

Differential forms and the geometry of general relativity

CERN Document Server

Dray, Tevian

2015-01-01

Differential Forms and the Geometry of General Relativity provides readers with a coherent path to understanding relativity. Requiring little more than calculus and some linear algebra, it helps readers learn just enough differential geometry to grasp the basics of general relativity.The book contains two intertwined but distinct halves. Designed for advanced undergraduate or beginning graduate students in mathematics or physics, most of the text requires little more than familiarity with calculus and linear algebra. The first half presents an introduction to general relativity that describes

Human exposure, health hazards, and environmental regulations

International Nuclear Information System (INIS)

Steinemann, Anne

2004-01-01

United States environmental regulations, intended to protect human health, generally fail to address major sources of pollutants that endanger human health. These sources are surprisingly close to us and within our control, such as consumer products and building materials that we use within our homes, workplaces, schools, and other indoor environments. Even though these indoor sources account for nearly 90% of our pollutant exposure, they are virtually unregulated by existing laws. Even pollutant levels found in typical homes, if found outdoors, would often violate federal environmental standards. This article examines the importance of human exposure as a way to understand and reduce effects of pollutants on human health. Results from exposure studies challenge traditional thinking about pollutant hazards, and reveal deficiencies in our patchwork of laws. And results from epidemiological studies, showing increases in exposure-related diseases, underscore the need for new protections. Because we cannot rely solely on regulations to protect us, and because health effects from exposures can develop insidiously, greater efforts are needed to reduce and prevent significant exposures before they occur. Recommendations include the development and use of safer alternatives to common products, public education on ways to reduce exposure, systematic monitoring of human exposure to pollutants, and a precautionary approach in decision-making

Differential diagnosis of CNS angiostrongyliasis: a short review.

Science.gov (United States)

Senthong, Vichai; Chindaprasirt, Jarin; Sawanyawisuth, Kittisak

2013-06-01

The diagnostic criterion for eosinophilic meningitis (EOM) is the identification of an absolute count of 10 eosinophils per ml or more than 10% of the total white blood cells in the cerebrospinal fluid (CSF) in the proper clinical context. The most common cause of EOM is Angiostrongylus cantonensis infection, termed meningitic angiostrongyliasis (MA). Neurognathostomiasis (NG) is the main parasitic disease in the differential diagnosis of meningitic angiostrongyliasis. This short review is based on articles published on Medline between 2000 and 2012 related to EOM. There are three main approaches that can be used to differentiate between MA and NG, involving clinical factors, history of larval exposure, and serological tests. MA patients presented with acute severe headache but without neurological deficit, combined with a history of eating uncooked snails or slugs. NG patients always presented with motor weakness, migratory swelling, radicular pain and had history of eating uncooked poultry or fish. Specific antigenic bands in immunoblot tests are helpful tools to differentiate the two diseases. Other causes of eosinophilic meningitis are neurocysticercosis, cerebral paragonimiasis, Toxoplasma canis, Baylisascaris, tuberculous meningitis, and cryptococcal meningitis.

Oxygen-controlled automated neural differentiation of mouse embryonic stem cells.

Science.gov (United States)

Mondragon-Teran, Paul; Tostoes, Rui; Mason, Chris; Lye, Gary J; Veraitch, Farlan S

2013-03-01

Automation and oxygen tension control are two tools that provide significant improvements to the reproducibility and efficiency of stem cell production processes. the aim of this study was to establish a novel automation platform capable of controlling oxygen tension during both the cell-culture and liquid-handling steps of neural differentiation processes. We built a bespoke automation platform, which enclosed a liquid-handling platform in a sterile, oxygen-controlled environment. An airtight connection was used to transfer cell culture plates to and from an automated oxygen-controlled incubator. Our results demonstrate that our system yielded comparable cell numbers, viabilities, metabolism profiles and differentiation efficiencies when compared with traditional manual processes. Interestingly, eliminating exposure to ambient conditions during the liquid-handling stage resulted in significant improvements in the yield of MAP2-positive neural cells, indicating that this level of control can improve differentiation processes. This article describes, for the first time, an automation platform capable of maintaining oxygen tension control during both the cell-culture and liquid-handling stages of a 2D embryonic stem cell differentiation process.

An Investigation of Organic and Inorganic Mercury Exposure and Blood Pressure in a Small-Scale Gold Mining Community in Ghana.

Science.gov (United States)

Rajaee, Mozhgon; Sánchez, Brisa N; Renne, Elisha P; Basu, Niladri

2015-08-21

There is increasing concern about the cardiovascular effects of mercury (Hg) exposure, and that organic methylmercury and inorganic Hg(2+) may affect the cardiovascular system and blood pressure differentially. In small-scale gold mining communities where inorganic, elemental Hg exposures are high, little is known about the effects of Hg on blood pressure. In 2011, we assessed the relationship between Hg exposure and blood pressure (BP) in a cross-sectional study of adults from a small-scale gold mining community, Kejetia, and subsistence farming community, Gorogo, in Ghana's Upper East Region. Participants' resting heart rate and BP were measured, and hair and urine samples were provided to serve as biomarkers of organic and inorganic Hg exposure, respectively. Participants included 70 miners and 26 non-miners from Kejetia and 75 non-miners from Gorogo. Total specific gravity-adjusted urinary and hair Hg was higher among Kejetia miners than Kejetia non-miners and Gorogo participants (median urinary Hg: 5.17, 1.18, and 0.154 µg/L, respectively; hair Hg: 0.945, 0.419, and 0.181 µg/g, respectively). Hypertension was prevalent in 17.7% of Kejetia and 21.3% of Gorogo participants. Urinary and hair Hg were not significantly associated with systolic or diastolic BP for Kejetia or Gorogo participants while adjusting for sex, age, and smoking status. Although our results follow trends seen in other studies, the associations were not of statistical significance. Given the unique study population and high exposures to inorganic Hg, the work contained here will help increase our understanding of the cardiovascular effects of Hg.

An Investigation of Organic and Inorganic Mercury Exposure and Blood Pressure in a Small-Scale Gold Mining Community in Ghana

Science.gov (United States)

Rajaee, Mozhgon; Sánchez, Brisa N.; Renne, Elisha P.; Basu, Niladri

2015-01-01

There is increasing concern about the cardiovascular effects of mercury (Hg) exposure, and that organic methylmercury and inorganic Hg2+ may affect the cardiovascular system and blood pressure differentially. In small-scale gold mining communities where inorganic, elemental Hg exposures are high, little is known about the effects of Hg on blood pressure. In 2011, we assessed the relationship between Hg exposure and blood pressure (BP) in a cross-sectional study of adults from a small-scale gold mining community, Kejetia, and subsistence farming community, Gorogo, in Ghana’s Upper East Region. Participants’ resting heart rate and BP were measured, and hair and urine samples were provided to serve as biomarkers of organic and inorganic Hg exposure, respectively. Participants included 70 miners and 26 non-miners from Kejetia and 75 non-miners from Gorogo. Total specific gravity-adjusted urinary and hair Hg was higher among Kejetia miners than Kejetia non-miners and Gorogo participants (median urinary Hg: 5.17, 1.18, and 0.154 µg/L, respectively; hair Hg: 0.945, 0.419, and 0.181 µg/g, respectively). Hypertension was prevalent in 17.7% of Kejetia and 21.3% of Gorogo participants. Urinary and hair Hg were not significantly associated with systolic or diastolic BP for Kejetia or Gorogo participants while adjusting for sex, age, and smoking status. Although our results follow trends seen in other studies, the associations were not of statistical significance. Given the unique study population and high exposures to inorganic Hg, the work contained here will help increase our understanding of the cardiovascular effects of Hg. PMID:26308023

Radiation exposures: risks and realities

International Nuclear Information System (INIS)

Ganesh, G.

2010-01-01

Discovery of radioactivity in 1869 by Henry Becquerel and artificial radioactivity by Irene Curie in 1934 led to the development of nuclear field and nuclear materials in 20th century. They are widely used for man-kind across the globe in electricity production, carbon dating, treatment and diagnosis of diseases etc. While deriving benefits and utilizing nuclear resources for the benefit of man-kind, it is inevitable that exposure to radiation can not be avoided. Radiation exists all around us either natural or man-made which can not be totally eliminated or avoided. Radiation exposures from natural background contribute 2.4 to 3.6 mSv in a year. Radiation exposures incurred by a member of public due to nuclear industries constitute less than one hundredth of annual dose due to natural background. Hence it is important to understand the risk posed by radiation and comparison of radiation risk with various risks arising due to other sources. Studies have indicated that risks due to environmental pollution, cigarette smoking, alcohol consumption, heart diseases are far higher in magnitude compared to radiation risks from man made sources. This paper brings about the details and awareness regarding radiation exposures, radiation risk, various risks associated with other industries and benefits of radiation exposures. (author)

Genome-Wide Expression Analysis of Human In Vivo Irritated Epidermis: Differential Profiles Induced by Sodium Lauryl Sulfate and Nonanoic Acid

DEFF Research Database (Denmark)

Clemmensen, Anders; Andersen, Klaus E; Clemmensen, Ole

2010-01-01

the differential molecular events induced in the epidermis by different irritants, we collected sequential biopsies ((1/2), 4, and 24 hours after a single exposure and at day 11 after repeated exposure) from human volunteers exposed to either sodium lauryl sulfate (SLS) or nonanoic acid (NON). Gene expression...

Isolated femoral hypoplasia: an intrauterine differential diagnosis to campomelia

Energy Technology Data Exchange (ETDEWEB)

Koerber, Friederike; Benz-Bohm, Gabriele [University of Cologne, Department of Paediatric Radiology, Cologne (Germany); Schoenau, Eckard [University of Cologne, Department of Paediatrics, Cologne (Germany); Horwitz, A.Eldad [Klinikum Krefeld, Department of Paediatric Radiology, Krefeld (Germany)

2005-06-01

The isolated form of femoral bowing is an important differential diagnosis of campomelia. Therefore, knowledge of isolated anomalies is fundamental for prenatal diagnosis, especially for the differential diagnosis from severe syndromes. Four cases are presented to discuss the differential diagnosis of femoral bowing including a review of the literature. We report four newborn babies with unilateral bowing and shortening of the femur. Three had no further anomaly; one child had additional abnormalities due to coumarin embryopathy. The radiological findings were shortened femora with bowing and varus deformity and cortical thickening on the concave side. All other parts showed normal bone structure. The aetiology of femoral bowing is unknown. Early damage of the cartilaginous model followed by remodelling with thickening on the concave side of the bone similar to the healing of malaligned fractures is suspected. The isolated form of femoral bowing without any other anomalies has to be differentiated from complex and more often severe congenital syndromes such as campomelia. Postpartum radiological examination should be reduced to a single exposure of the affected limb and follow-up should be done by clinical examination. (orig.)

Differentiating for Multiple Intelligences: A Study of Students' Understandings through the Use of Aesthetic Representations

Science.gov (United States)

Crim, Courtney L.; Kennedy, Kimberley D.; Thornton, Jenifer S.

2013-01-01

This article reviews the relevant literature in regard to differentiation, multiple intelligences, and aesthetic representations. Next, it presents the methodology, reports findings, and discusses themes related to the authors' research questions. Finally, it concludes that tapping into students' multiple intelligence strength(s) is an excellent…

Osteoclast differentiation inhibitors: a patent review (2008 - 2012).

Science.gov (United States)

Kim, Seong Hwan; Moon, Seong-Hee

2013-12-01

Mononuclear macrophage/monocyte-lineage hematopoietic precursors differentiate into multinucleated osteoclasts. Abnormally increased numbers and/or overactivation of osteoclasts can lead to bone loss. Therefore, pharmaceutical inhibition of osteoclast differentiation is one therapeutic strategy for mitigating the occurrence of bone loss-associated disorders and related fractures. This review surveys the patents and patent applications from 2008 to 2012 that are related to inventions of therapeutics and/or methods for inhibiting osteoclast differentiation. Over the past 20 years, the identification and validation of signaling molecules involved in osteoclast differentiation has led to a better understanding of the molecular mechanism, and to the development of new therapeutic agents for treating bone loss-associated disorders. Since 2008, 34 WO patents or patent applications have been filed that relate to inventions of therapeutics and/or methods for chemical-based, natural product-based, or biological-based inhibitors of osteoclast differentiation. Here, analysis of these patents and patent applications is presented, and summarize the disclosed osteoclast differentiation-inhibiting target molecules. This report can support further advances in the development of anti-osteoclastogenic therapeutics for bone loss-associated disorders, including osteoporosis, rheumatoid arthritis, Paget's disease, periodontal disease, osteosarcoma, and cancer bone metastasis.

Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development

International Nuclear Information System (INIS)

Cheng, Xin; Chen, Jian-long; Ma, Zheng-lai; Zhang, Zhao-long; Lv, Shun; Mai, Dong-mei; Liu, Jia-jia; Chuai, Manli; Lee, Kenneth Ka Ho; Wan, Chao; Yang, Xuesong

2014-01-01

Dexamethasone (Dex) has anti-inflammatory and immunomodulatory properties against many conditions. There is a potential teratogenic risk, however, for pregnant women receiving Dex treatment. It has been claimed that Dex exposure during pregnancy could affect osteogenesis in the developing embryo, which still remains highly controversial. In this study, we employed chick embryos to investigate the effects of Dex exposure on skeletal development using combined in vivo and in vitro approach. First, we demonstrated that Dex (10 −8 –10 −6 μmol/egg) exposure resulted in a shortening of the developing long bones of chick embryos, and it accelerated the deposition of calcium salts. Secondly, histological analysis of chick embryo phalanxes exhibited Dex exposure inhibited the proliferation of chondrocytes, increased apoptosis of chondrocytes and osteocytes, and led to atypical arranged hypertrophic chondrocytes. The expression of genes related to skeletogenesis was also analyzed by semi-quantitative RT-PCR. The expression of ALP, Col1a2 and Col2a1 was decreased in the Dex treated phalanxes. A detectable increase was observed in Runx-2 and Mmp-13 expression. We next examined how Dex affected the different stages of skeletogenesis in vitro. Utilizing limb bud mesenchyme micromass cultures, we determined that Dex exposure exerted no effect on apoptosis but impaired chondrogenic cell proliferation. Interestingly, low dose of Dex moderately prompted nodule formation as revealed by alcian blue staining, but higher doses of Dex significantly inhibited similar chondrogenic differentiation. Dex exposure did not induce apoptosis when the chondrogenic precursors were still at the mesenchymal stage, however, cell viability was suppressed when the mesenchyme differentiated into chondrocytes. Alizarin red staining revealed that the capacity to form mineralized bone nodules was correspondingly enhanced as Dex concentrations increased. The mRNA level of Sox-9 was slightly increased

Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development

Energy Technology Data Exchange (ETDEWEB)

Cheng, Xin; Chen, Jian-long; Ma, Zheng-lai; Zhang, Zhao-long; Lv, Shun; Mai, Dong-mei; Liu, Jia-jia [Department of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Medicine, Jinan University, Guangzhou 510632 (China); Chuai, Manli [Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH (United Kingdom); Lee, Kenneth Ka Ho; Wan, Chao [Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin (Hong Kong); Yang, Xuesong, E-mail: yang_xuesong@126.com [Department of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Medicine, Jinan University, Guangzhou 510632 (China); Institute of Fetal-Preterm Labor Medicine, Jinan University, Guangzhou 510632 (China)

2014-11-15

Dexamethasone (Dex) has anti-inflammatory and immunomodulatory properties against many conditions. There is a potential teratogenic risk, however, for pregnant women receiving Dex treatment. It has been claimed that Dex exposure during pregnancy could affect osteogenesis in the developing embryo, which still remains highly controversial. In this study, we employed chick embryos to investigate the effects of Dex exposure on skeletal development using combined in vivo and in vitro approach. First, we demonstrated that Dex (10{sup −8}–10{sup −6} μmol/egg) exposure resulted in a shortening of the developing long bones of chick embryos, and it accelerated the deposition of calcium salts. Secondly, histological analysis of chick embryo phalanxes exhibited Dex exposure inhibited the proliferation of chondrocytes, increased apoptosis of chondrocytes and osteocytes, and led to atypical arranged hypertrophic chondrocytes. The expression of genes related to skeletogenesis was also analyzed by semi-quantitative RT-PCR. The expression of ALP, Col1a2 and Col2a1 was decreased in the Dex treated phalanxes. A detectable increase was observed in Runx-2 and Mmp-13 expression. We next examined how Dex affected the different stages of skeletogenesis in vitro. Utilizing limb bud mesenchyme micromass cultures, we determined that Dex exposure exerted no effect on apoptosis but impaired chondrogenic cell proliferation. Interestingly, low dose of Dex moderately prompted nodule formation as revealed by alcian blue staining, but higher doses of Dex significantly inhibited similar chondrogenic differentiation. Dex exposure did not induce apoptosis when the chondrogenic precursors were still at the mesenchymal stage, however, cell viability was suppressed when the mesenchyme differentiated into chondrocytes. Alizarin red staining revealed that the capacity to form mineralized bone nodules was correspondingly enhanced as Dex concentrations increased. The mRNA level of Sox-9 was slightly

Youth Exposure to Violence in an Urban Setting

OpenAIRE

Seal, David; Nguyen, Annie; Beyer, Kirsten

2014-01-01

To inform a city-wide youth Violence Prevention Initiative, we explored youth narratives about their exposure to violence to gain insight into their understanding of the causes and effects of violence in their communities. At-risk youth were recruited through street outreach for individual interviews and focus group sessions. Types of experiential violence identified included (1) street, (2) family/interpersonal, (3) school, (4) indirect exposure (e.g., neighborhood crime), and (5) prejudice/...

Mesenchymal Stem Cells Retain Their Defining Stem Cell Characteristics After Exposure to Ionizing Radiation

International Nuclear Information System (INIS)

Nicolay, Nils H.; Sommer, Eva; Lopez, Ramon; Wirkner, Ute; Trinh, Thuy; Sisombath, Sonevisay; Debus, Jürgen; Ho, Anthony D.; Saffrich, Rainer; Huber, Peter E.

2013-01-01

Purpose: Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown. Methods and Materials: Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays. Results: MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR. Conclusions: These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression

Professional Niche Differentiation: Understanding Dai (Traditional Midwife Survival in Rural Rajasthan

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Sharmeen Azher

2017-04-01

Full Text Available Prescribing medicine, providing contraception, delivering babies – although we may turn to physicians, rural Rajasthani women turn to Barefoot Doctors out of necessity. Such care is available courtesy of the Barefoot College, a pioneering NGO that transforms the skills of the illiterate poor into local infrastructure. Barefoot Doctors are innovative because of their origins as dais (traditional midwives; once abundant across South Asia, dais are mostly extinct due to government/NGO interventions emphasizing “modernity”, like the Accredited Social Health Activist program. Why, then, have dais survived as Barefoot Doctors when they are extinct elsewhere? Ecological niche differentiation refers to when competing species successfully coexist; one species adapts to fulfill another role. Using over fifty interviews with stakeholders, I explain the persistence of Barefoot Doctors as health resources using “professional niche differentiation”. Barefoot Doctors exemplify how health infrastructure can be sustainable in resource-poor settings when created according to local needs and ideologies.

The Occupational Cost of Being Illegal in the United States: Legal Status, Job Hazards, and Compensating Differentials.

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Hall, Matthew; Greenman, Emily

2015-01-01

Considerable research and pervasive cultural narratives suggest that undocumented immigrant workers are concentrated in the most dangerous, hazardous, and otherwise unappealing jobs in U.S. labor markets. Yet, owing largely to data limitations, little empirical work has addressed this topic. Using data from the 2004 and 2008 panels of the Survey of Income and Program Participation, we impute legal status for Mexican and Central American immigrants and link their occupations to BLS data on occupational fatalities and occupational hazard data from the Department of Labor to explore racial and legal status differentials on several specific measures of occupational risk. Results indicate that undocumented workers face heightened exposure to numerous dimensions of occupational hazard - including higher levels of physical strain, exposure to heights, and repetitive motions - but are less exposed than native workers to some of the potentially most dangerous environments. We also show that undocumented workers are rewarded less for employment in hazardous settings, receiving low or no compensating differential for working in jobs with high fatality, toxic materials, or exposure to heights. Overall, this study suggests that legal status plays an important role in determining exposure to job hazard and in structuring the wage returns to risky work.

The usefulness of Schwartz's 'Values Theory' in understanding consumer behaviour towards differentiated products

DEFF Research Database (Denmark)

Krystallis Krontalis, Athanasios; Vassallo, M.; Chryssochoidis, G.

2012-01-01

The Values Theory adopts a generic framework whereby a set of values is employed across consumer decision-making contexts in a manner that makes no distinction among various product categories. The present study advances this theory by exhibiting the adaptation capability of the generic values...... instrument (the Portrait Value Questionnaire, PVQ), demonstrating that tailor-made PVQ versions can reflect consumers’ motives towards differentiated products (i.e. organic foods). A questionnaire was completed by approximately 1000 households in each of eight EU countries (N = 8171). The organic food...

Differential forms for scientists and engineers

Science.gov (United States)

Blair Perot, J.; Zusi, Christopher J.

2014-01-01

This paper is a review of a number of mathematical concepts from differential geometry and exterior calculus that are finding increasing application in the numerical solution of partial differential equations. The objective of the paper is to introduce the scientist/ engineer to some of these ideas via a number of concrete examples in 2, 3, and 4 dimensions. The goal is not to explain these ideas with mathematical precision but to present concrete examples and enable a physical intuition of these concepts for those who are not mathematicians. The objective of this paper is to provide enough context so that scientist/engineers can interpret, implement, and understand other works which use these elegant mathematical concepts.

Enhanced differentiation of neural stem cells to neurons and promotion of neurite outgrowth by oxygen-glucose deprivation.

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Wang, Qin; Yang, Lin; Wang, Yaping

2015-06-01

Stroke has become the leading cause of mortality worldwide. Hypoxic or ischemic insults are crucial factors mediating the neural damage in the brain tissue of stroke patients. Neural stem cells (NSCs) have been recognized as a promising tool for the treatment of ischemic stroke and other neurodegenerative diseases due to their inducible pluripotency. In this study, we aim to mimick the cerebral hypoxic-ischemic injury in vitro using oxygen-glucose deprivation (OGD) strategy, and evaluate the effects of OGD on the NSC's neural differentiation, as well as the differentiated neurite outgrowth. Our data showed that NSCs under the short-term 2h OGD treatment are able to maintain cell viability and the capability to form neurospheres. Importantly, this moderate OGD treatment promotes NSC differentiation to neurons and enhances the performance of the mature neuronal networks, accompanying increased neurite outgrowth of differentiated neurons. However, long-term 6h and 8h OGD exposures in NSCs lead to decreased cell survival, reduced differentiation and diminished NSC-derived neurite outgrowth. The expressions of neuron-specific microtubule-associated protein 2 (MAP-2) and growth associated protein 43 (GAP-43) are increased by short-term OGD treatments but suppressed by long-term OGD. Overall, our results demonstrate that short-term OGD exposure in vitro induces differentiation of NSCs while maintaining their proliferation and survival, providing valuable insights of adopting NSC-based therapy for ischemic stroke and other neurodegenerative disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Creation of a retrospective job-exposure matrix using surrogate measures of exposure for a cohort of US career firefighters from San Francisco, Chicago and Philadelphia.

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Dahm, Matthew M; Bertke, Stephen; Allee, Steve; Daniels, Robert D

2015-09-01

To construct a cohort-specific job-exposure matrix (JEM) using surrogate metrics of exposure for a cancer study on career firefighters from the Chicago, Philadelphia and San Francisco Fire Departments. Departmental work history records, along with data on historical annual fire-runs and hours, were collected from 1950 to 2009 and coded into separate databases. These data were used to create a JEM based on standardised job titles and fire apparatus assignments using several surrogate exposure metrics to estimate firefighters' exposure to the combustion byproducts of fire. The metrics included duration of exposure (cumulative time with a standardised exposed job title and assignment), fire-runs (cumulative events of potential fire exposure) and time at fire (cumulative hours of potential fire exposure). The JEM consisted of 2298 unique job titles alongside 16,174 fire apparatus assignments from the three departments, which were collapsed into 15 standardised job titles and 15 standardised job assignments. Correlations were found between fire-runs and time at fires (Pearson coefficient=0.92), duration of exposure and time at fires (Pearson coefficient=0.85), and duration of exposure and fire-runs (Pearson coefficient=0.82). Total misclassification rates were found to be between 16-30% when using duration of employment as an exposure surrogate, which has been traditionally used in most epidemiological studies, compared with using the duration of exposure surrogate metric. The constructed JEM successfully differentiated firefighters based on gradient levels of potential exposure to the combustion byproducts of fire using multiple surrogate exposure metrics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Transcriptional differences between smokers and non-smokers and variance by obesity as a risk factor for human sensitivity to environmental exposures.

Science.gov (United States)

Nikodemova, Maria; Yee, Jeremiah; Carney, Patrick R; Bradfield, Christopher A; Malecki, Kristen Mc

2018-04-01

Obesity has been shown to alter response to air pollution and smoking but underlying biological mechanisms are largely unknown and few studies have explored mechanisms by which obesity increases human sensitivity to environmental exposures. Overall study goals were to investigate whole blood gene expression in smokers and non-smokers to examine associations between cigarette smoke and changes in gene expression by obesity status and test for effect modification. Relative fold-change in mRNA expression levels of 84 genes were analyzed using a Toxicity and Stress PCR array among 50 21-54 year old adults. Data on smoking status was confirmed using urinary cotinine levels. Adjusted models included age, gender, white blood cell count and body-mass index. Models comparing gene expression of smokers vs. non-smokers identified six differentially expressed genes associated with smoking after adjustments for covariates. Obesity was associated with 29 genes differentially expressed compared to non-obese. We also identified 9 genes with significant smoking/obesity interactions influencing mRNA levels in adjusted models comparing expression between smokers vs non-smokers for four DNA damage related genes (GADD45A, DDB2, RAD51 and P53), two oxidative stress genes (FTH1, TXN), two hypoxia response genes (BN1P3lL, ARNT), and one gene associated with unfolded protein response (ATF6B). Findings suggest that obesity alters human sensitivity to smoke exposures through several biological pathways by modifying gene expression. Additional studies are needed to fully understand the clinical impact of these effects, but risk assessments should consider underlying phenotypes, such as obesity, that may modulate sensitivity of vulnerable populations to environmental exposures. Copyright © 2018 Elsevier Ltd. All rights reserved.

Expression of assayable residual stem cell damage in erythroid differentiation

International Nuclear Information System (INIS)

Huebner, G.E.; Miller, M.E.; Cronkite, E.P.

1985-01-01

In rodents, residual damage is inducible in hematopoietic stem cells by exposure to ionizing radiation or alkylating agents. This damage can b e assayed in mice by transferring bone marrow into lethally irradiated syngeneic recipients and subsequently measuring the incremental increase of-( 125 I)iodo-2'-deoxyuridine incorporation in spleens. In this study, bone marrow from mice treated 3 weeks previously with Methylnitrosourea (50 mg/kg) or 450 rad was injected into recipients in order to determine possible residual effects of treatment of erythroid cell differentiation following stem cell seeding. Such effects were detected by a reduced amount of 59 Fe incorporation into spleens, thus indicatin g transfer of residual stem cell damage to differentiating cells. (orig.)

Global differential geometry: An introduction for control engineers

Science.gov (United States)

Doolin, B. F.; Martin, C. F.

1982-01-01

The basic concepts and terminology of modern global differential geometry are discussed as an introduction to the Lie theory of differential equations and to the role of Grassmannians in control systems analysis. To reach these topics, the fundamental notions of manifolds, tangent spaces, vector fields, and Lie algebras are discussed and exemplified. An appendix reviews such concepts needed for vector calculus as open and closed sets, compactness, continuity, and derivative. Although the content is mathematical, this is not a mathematical treatise but rather a text for engineers to understand geometric and nonlinear control.

Symptom patterns related to traumatic exposure among female inmates with and without a diagnosis of posttraumatic stress disorder.

Science.gov (United States)

Warren, Janet I; Loper, Ann Booker; Komarovskaya, Irina

2009-01-01

Our study examines the trauma-related experiences of 203 female prison inmates, most of whom had experienced chronic trauma throughout their lives but among whom only 51 percent met diagnostic criteria for PTSD. We used the two groups to study differences in trauma exposure and pre-existent psychopathology as they related to the emergence of full diagnostic criteria for PTSD. We also used the entire sample to explore the factor structure and endorsement frequencies of each symptom category as it related to trauma exposure. Our analyses indicated that the PTSD group differed from the non-PTSD group in the number of life traumas each group had experienced and the pre-existence of borderline personality disorder. Five symptoms accurately differentiated the two groups, with an 86 percent correct classification: recurrent thoughts, amnesia, loss of interest, difficulty concentrating, and a heightened startle response. An exploratory factor analysis further suggested two primary factors: intrusion and arousal. We apply our findings to the naturalistic versus interactional debate surrounding the disorder and reflect on the endorsement frequencies as they might inform our understanding of malingering as it occurs in legal and forensic settings.

Maltreatment Exposure, Brain Structure, and Fear Conditioning in Children and Adolescents.

Science.gov (United States)

McLaughlin, Katie A; Sheridan, Margaret A; Gold, Andrea L; Duys, Andrea; Lambert, Hilary K; Peverill, Matthew; Heleniak, Charlotte; Shechner, Tomer; Wojcieszak, Zuzanna; Pine, Daniel S

2016-07-01

Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n=94) aged 6-18 years, 40.4% (n=38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells as conditioned stimuli (CS+/CS-) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self-reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. Children without maltreatment exposure exhibited strong differential conditioning to the CS+ vs CS-, based on SCR and self-reported fear. In contrast, maltreated children exhibited blunted SCR to the CS+ and failed to exhibit differential SCR to the CS+ vs CS- during early conditioning. Amygdala and hippocampal volume were reduced among children with maltreatment exposure and were negatively associated with SCR to the CS+ during early conditioning in the total sample, although these associations were negative only among non-maltreated children and were positive among maltreated children. The association of maltreatment with externalizing psychopathology was mediated by this perturbed pattern of fear conditioning. Child maltreatment is associated with failure to discriminate between threat and safety cues during fear conditioning in children. Poor threat-safety discrimination might reflect either enhanced fear generalization or a deficit in associative learning, which may in turn represent a central mechanism underlying the development of maltreatment-related externalizing psychopathology in children.

Induction of glutathione synthesis in human hepatocytes by acute and chronic arsenic exposure: Differential roles of mitogen-activated protein kinases

International Nuclear Information System (INIS)

Hou, Yongyong; Wang, Yi; Wang, Huihui; Xu, Yuanyuan

2014-01-01

Highlights: • Arsenic exposure increased intracellular levels of glutathione. • Mitogen-activated protein kinases were involved in glutathione homeostasis. • ERK contributed to glutathione synthesis during acute arsenic exposure. • Glutathione synthesis was regulated by p38 at least in part independent of NRF2 during chronic arsenic exposure. - Abstract: Glutathione (GSH) is a vital component of antioxidant defense which protects cells from toxic insults. Previously we found intracellular GSH was involved in cell resistance against arsenic-induced cytotoxicity. However, molecular mechanisms of GSH homeostasis during arsenic exposure are largely undefined. Here, we investigated roles of mitogen-activated protein kinases (MAPKs) in GSH synthesis pathway with two arsenic exposure strategies by using Chang human hepatocytes. In one strategy, acute arsenic exposure (20 μM, 24 h) was applied, as MAPK signaling is generally considered to be transient. In the other one, chronic arsenic exposure (500 nM, 20 weeks) was applied, which mimicked the general human exposure to arsenic. We found that acute arsenic exposure activated extracellular signal-regulated 1/2 kinases (ERK1/2) and c-Jun N-terminal kinase (JNK) in parallel with increased transcription and nuclear translocation of factor-erythroid 2-related factor 2 (NRF2) and enhanced expression of γ-glutamyl cysteine ligase catalytic subunit (GCLC), resulting in elevated intracellular GSH levels. Specific ERK inhibitor abolished arsenic-induced NRF2 nuclear translocation and GSH synthesis. During chronic arsenic exposure which induced a malignant cellular phenotype, continuous p38 activation and NRF2 nuclear translocation were observed with enhanced GSH synthesis. Specific p38 inhibitor attenuated arsenic-enhanced GSH synthesis without changing NRF2 nuclear translocation. Taken together, our results indicate MAPK pathways play an important role in cellular GSH homeostasis in response to arsenic. However, the

Human exposure to aluminium.

Science.gov (United States)

Exley, Christopher

2013-10-01

Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

Sex-Specific Effects of Combined Exposure to Chemical and Non-chemical Stressors on Neuroendocrine Development: a Review of Recent Findings and Putative Mechanisms.

Science.gov (United States)

Cowell, Whitney J; Wright, Rosalind J

2017-12-01

Environmental toxicants and psychosocial stressors share many biological substrates and influence overlapping physiological pathways. Increasing evidence indicates stress-induced changes to the maternal milieu may prime rapidly developing physiological systems for disruption by concurrent or subsequent exposure to environmental chemicals. In this review, we highlight putative mechanisms underlying sex-specific susceptibility of the developing neuroendocrine system to the joint effects of stress or stress correlates and environmental toxicants (bisphenol A, alcohol, phthalates, lead, chlorpyrifos, and traffic-related air pollution). We provide evidence indicating that concurrent or tandem exposure to chemical and non-chemical stressors during windows of rapid development is associated with sex-specific synergistic, potentiated and reversed effects on several neuroendocrine endpoints related to hypothalamic-pituitary-adrenal axis function, sex steroid levels, neurotransmitter circuits, and innate immune function. We additionally identify gaps, such as the role that the endocrine-active placenta plays, in our understanding of these complex interactions. Finally, we discuss future research needs, including the investigation of non-hormonal biomarkers of stress. We demonstrate multiple physiologic systems are impacted by joint exposure to chemical and non-chemical stressors differentially among males and females. Collectively, the results highlight the importance of evaluating sex-specific endpoints when investigating the neuroendocrine system and underscore the need to examine exposure to chemical toxicants within the context of the social environment.

Well differentiated papillary mesothelioma of abdomen- a rare case with diagnostic dilemma.

Science.gov (United States)

Saha, Aniruddha; Mandal, Palash Kumar; Manna, Anupam; Khan, Kalyan; Pal, Subrata

2018-01-01

Well-differentiated papillary mesothelioma is a rare tumor occurring predominantly in the peritoneum of young women, a few with history of asbestos exposure. A 28-year-old woman presented with ascites and pain abdomen. Ultrasonography and computed tomography scan of the abdomen revealed a mass in the retroperitoneum measuring 15 cm × 12 cm. Histopathological examination along with immunohistochemistry (IHC) confirmed it to be a papillary mesothelioma in the peritoneum. It is difficult to differentiate from more common malignant mesothelioma and papillary adenocarcinoma, which also have poorer prognosis. The difficulty can be resolved by clinico-radiological correlation along with histopathological examination and IHC.

INF-γ Enhances Nox2 Activity by Upregulating phox Proteins When Applied to Differentiating PLB-985 Cells but Does Not Induce Nox2 Activity by Itself.

Directory of Open Access Journals (Sweden)

Michael A Ellison

Full Text Available The cytokine and drug interferon-γ enhances superoxide anion production by the antimicrobicidal Nox2 enzyme of neutrophils. Because mature neutrophils have a short lifespan, we hypothesized that the effects of interferon-γ on these cells might be mediated by its prolonged exposure to differentiating neutrophil precursors in the bone marrow rather than its brief exposure to mature circulating neutrophils. Effects of INF-Γ on NOX2 activity: To address this possibility we exposed the myeloid PLB-985 cell line to interferon-γ for 3 days in the presence of dimethyl sulfoxide which induces terminal differentiation of these cells. Interferon-γ was found to enhance superoxide production by Nox2 in a concentration dependent manner. In contrast, application of interferon-γ alone for 3 days failed to induce detectible Nox2 activity. Additionally, application of interferon-γ for 3 hours to pre-differentiated PLB-985 cells, which models studies using isolated neutrophils, was much less effective at enhancing superoxide anion production. Effects of INF-Γ on phox protein levels: Addition of interferon-γ during differentiation was found to upregulate the Nox2 proteins gp91phox and p47phox in concert with elevated transcription of their genes. The p22phox protein was upregulated in the absence of increased transcription presumably reflecting stabilization resulting from binding to the elevated gp91phox. Thus, increased levels of gp91phox, p47phox and p22phox likely account for the interferon-γ mediated enhancement of dimethyl sulfoxide-induced Nox2 activity. In contrast, although interferon-γ alone also increased various phox proteins and their mRNAs, the pattern was very different to that seen with interferon-γ plus dimethyl sulfoxide. In particular, p47phox was not induced thus explaining the inability of interferon -γ alone to enhance Nox2 activity. Short application of interferon-γ to already differentiated cells failed to increase any phox

The epigenomics of embryonic stem cell differentiation.

Science.gov (United States)

Kraushaar, Daniel C; Zhao, Keji

2013-01-01

Embryonic stem cells (ESCs) possess an open and highly dynamic chromatin landscape, which underlies their plasticity and ultimately maintains ESC pluripotency. The ESC epigenome must not only maintain the transcription of pluripotency-associated genes but must also, through gene priming, facilitate rapid and cell type-specific activation of developmental genes upon lineage commitment. Trans-generational inheritance ensures that the ESC chromatin state is stably transmitted from one generation to the next; yet at the same time, epigenetic marks are highly dynamic, reversible and responsive to extracellular cues. Once committed to differentiation, the ESC epigenome is remodeled and resolves into a more compact chromatin state. A thorough understanding of the role of chromatin modifiers in ESC fate and differentiation will be important if they are to be used for therapeutic purposes. Recent technical advances, particularly in next-generation sequencing technologies, have provided a genome-scale view of epigenetic marks and chromatin modifiers. More affordable and faster sequencing platforms have led to a comprehensive characterization of the ESC epigenome and epigenomes of differentiated cell types. In this review, we summarize and discuss the recent progress that has highlighted the central role of histone modifications, histone variants, DNA methylation and chromatin modifiers in ESC pluripotency and ESC fate. We provide a detailed and comprehensive discussion of genome-wide studies that are pertinent to our understanding of mammalian development.

LEUKOCYTE DIFFERENTIAL OF ANGUILLID EEL, Anguilla bicolor McClelland, EXPOSED TO VARIED SALINITIES

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Fita Fatimah

2017-06-01

Full Text Available The anguillid eel is a catadromous eel capable of inhabiting freshwater growth habitat and seawater spawning habitat throughout their life cycle. At the juvenile to mature stage, they inhabit freshwater then migrate to marine water to spawn. Changes in salinity, which is one of the stressful environmental factors for the eel, affect their physiological condition by increasing the leukocytes number. This increase is an adaptation method to improve their immune system as a response to salinity change. This study intended to evaluate the leukocyte differential of anguillid eel (Anguilla bicolor McClelland exposed to various salinities. This research applied a Completely Randomized Design. The treatment was three levels of saline media including 4 ppt, 15 ppt, and 30 ppt with five replicates. The independent variable was the different salinity, and the dependent variable was the leukocyte differential. The parameters measured consisted of the different percentage of neutrophils, lymphocytes, monocytes, and eosinophils in which the measurements administered after two months of the eel exposure. We analyzed the data with ANOVA at the confidence level of 95%. The results showed that exposure of salinity significantly affected the percentage of leukocyte differential (P < 0.05. The increase in salinity decreased the neutrophils and monocytes, but increased the lymphocytes, and showed no effect on eosinophils.

Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood.

Science.gov (United States)

Solomon, Olivia; Yousefi, Paul; Huen, Karen; Gunier, Robert B; Escudero-Fung, Maria; Barcellos, Lisa F; Eskenazi, Brenda; Holland, Nina

2017-07-01

Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Phthalates are known endocrine disruptors with ubiquitous exposures in the general population including pregnant women, and they have been linked with a number of adverse health outcomes. We examined the association between in utero phthalate exposure and altered patterns of cord blood DNA methylation in 336 Mexican-American newborns. Concentrations of 11 phthalate metabolites were analyzed in maternal urine samples collected at 13 and 26 weeks gestation as a measure of fetal exposure. DNA methylation was assessed using the Infinium HumanMethylation 450K BeadChip adjusting for cord blood cell composition. To identify differentially methylated regions (DMRs) that may be more informative than individual CpG sites, we used two different approaches, DMRcate and comb-p. Regional assessment by both methods identified 27 distinct DMRs, the majority of which were in relation to multiple phthalate metabolites. Most of the significant DMRs (67%) were observed for later pregnancy (26 weeks gestation). Further, 51% of the significant DMRs were associated with the di-(2-ethylhexyl) phthalate metabolites. Five individual CpG sites were associated with phthalate metabolite concentrations after multiple comparisons adjustment (FDR), all showing hypermethylation. Genes with DMRs were involved in inflammatory response (IRAK4 and ESM1), cancer (BRCA1 and LASP1), endocrine function (CNPY1), and male fertility (IFT140, TESC, and PRDM8). These results on differential DNA methylation in newborns with prenatal phthalate exposure provide new insights and targets to explore mechanism of adverse effects of phthalates on human health. Environ. Mol. Mutagen. 58:398-410, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Repeated exposure to immobilization or two different footshock intensities reveals differential adaptation of the hypothalamic-pituitary-adrenal axis.

Science.gov (United States)

Rabasa, Cristina; Muñoz-Abellán, Cristina; Daviu, Núria; Nadal, Roser; Armario, Antonio

2011-05-03

Factors involved in adaptation to repeated stress are not well-characterized. For instance, acute footshock (FS) of high intensity appears to be less severe than immobilization (IMO) in light of the speed of post-stress recovery of the hypothalamic-pituitary-adrenal (HPA) axis and other physiological variables. However, repeated exposure to IMO consistently resulted in reduction of the HPA response to the same stressor (adaptation), whereas failure to adapt has been usually reported after FS. Thus, in the present work we directly compared the activation of HPA axis and other physiological changes in response to both acute and repeated exposure to IMO and two intensities of FS (medium and high) in adult male rats. Control rats were exposed to the FS boxes but they did not receive shocks. Daily repeated exposure to IMO resulted in significant adaptation of the overall ACTH and corticosterone responses to the stressor. Such a reduction was also observed with repeated exposure to FS boxes and FS-medium, whereas repeated exposure to FS-high only resulted in a small reduction of the corticosterone response during the post-stress period. This suggests that some properties of FS-high make adaptation to it difficult. Interestingly, overall changes in food intake and body weight gain throughout the week of exposure to the stressors reveal a greater impact of IMO than FS-high, indicating that factors other than the intensity of a stressor, at least when evaluated in function of the above physiological variables, can influence HPA adaptation. Since FS exposure is likely to cause more pain than IMO, activation of nociceptive signals above a certain level may negatively affect HPA adaptation to repeated stressors. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of gold nanoparticles on adipogenic differentiation of human mesenchymal stem cells

International Nuclear Information System (INIS)

Kohl, Yvonne; Gorjup, Erwin; Katsen-Globa, Alisa; Büchel, Claudia; Briesen, Hagen von; Thielecke, Hagen

2011-01-01

Gold nanoparticles are very attractive for biomedical products. However, there is a serious lack of information concerning the biological activity of nanosized gold in human tissue cells. An influence of nanoparticles on stem cells might lead to unforeseen consequences to organ and tissue functions as long as all cells arising from the initial stem cell might be subsequently damaged. Therefore the effect of negatively charged gold nanoparticles (9 and 95 nm), which are certified as reference material for preclinical biomedical research, on the adipogenic differentiation of human mesenchymal stem cells (hMSCs) is investigated here. Bone marrow hMSCs are chosen as differentiation model since bone marrow hMSCs are well characterized and their differentiation into the adipogenic lineage shows clear and easily detectable differentiation. In this study effects of gold nanoparticles on adipogenic differentiation are analyzed regarding fat storage and mitochondrial activity after different exposure times (4–21 days). Using time lapse microscopy the differentiation progress under chronically gold nanoparticle treatment is continuously investigated. In this preliminary study, chronically treatment of adipogenic differentiating hMSCs with gold nanoparticles resulted in a reduced number and size of lipid vacuoles and reduced mitochondrial activity depending on the applied concentration and the surface charge of the particles.

Effect of gold nanoparticles on adipogenic differentiation of human mesenchymal stem cells

Science.gov (United States)

Kohl, Yvonne; Gorjup, Erwin; Katsen-Globa, Alisa; Büchel, Claudia; von Briesen, Hagen; Thielecke, Hagen

2011-12-01

Gold nanoparticles are very attractive for biomedical products. However, there is a serious lack of information concerning the biological activity of nanosized gold in human tissue cells. An influence of nanoparticles on stem cells might lead to unforeseen consequences to organ and tissue functions as long as all cells arising from the initial stem cell might be subsequently damaged. Therefore the effect of negatively charged gold nanoparticles (9 and 95 nm), which are certified as reference material for preclinical biomedical research, on the adipogenic differentiation of human mesenchymal stem cells (hMSCs) is investigated here. Bone marrow hMSCs are chosen as differentiation model since bone marrow hMSCs are well characterized and their differentiation into the adipogenic lineage shows clear and easily detectable differentiation. In this study effects of gold nanoparticles on adipogenic differentiation are analyzed regarding fat storage and mitochondrial activity after different exposure times (4-21 days). Using time lapse microscopy the differentiation progress under chronically gold nanoparticle treatment is continuously investigated. In this preliminary study, chronically treatment of adipogenic differentiating hMSCs with gold nanoparticles resulted in a reduced number and size of lipid vacuoles and reduced mitochondrial activity depending on the applied concentration and the surface charge of the particles.

Understanding the radiosensitivity of hematopoietic stem cells through CDNA micro-arrays profiling

Energy Technology Data Exchange (ETDEWEB)

Pawlik, A.; Cebo, Ch.; Vaigot, P.; Tronik-Le Roux, D. [Evry Univ., Lab. de Genomique et Radiobiologie de l' Hematopoiese, Service de Genomique Fonctionnelle, CEA, 91 (France)

2006-07-01

Eradication of circulating hematopoietic cells has been long known to be the first noticeable somatic effect following total body ionizing radiation (IR) exposure. Among these hematopoietic cells a marked differences in sensitivity to IR have been documented reflecting the remarkable degree of heterogeneity in cell type, proliferative capacity and cell cycle status within the bone marrow cells. From all the hematopoietic cells, the small lymphocyte has the greatest radiosensitivity. In fact, a decline in absolute lymphocyte count has been used to assess IR dose in the early phase of observation after IR exposure. At moderate doses, bone marrow recovery is triggered by the differentiation of stem/early progenitor cells, which confirms further their differential sensitivity to radiation exposure. Although differences in radiosensitivity of the stem cell pool have also been documented, little is known from a molecular viewpoint. To gain insight into the molecular programs underlying the response o f hematopoietic cells to radiation exposure, we have applied a genome wide analysis strategy based on cDNA micro arrays. This technology offers a unique opportunity to dissect complex biological process by assessing three types of questions, which are, in order of complexity: Which genes are differentially expressed among the samples studied:Which genes are expressed in a coordinated manner and what are the regulators involved,what are the global biological pathways mobilized. To answer these questions transcriptional changes occurring after exposure of mice to whole body irradiation (2 Gy) were monitored in bone marrow and spleen. The time course was established in vivo and encompassed the reversible eradication of cells. For each kinetic point RNA was collected from both, spleen or sorted B.M. populations from irradiated and sham irradiated mice. The sham irradiated mice were used to eliminate stress modifications due to handling.The results highlight numerous

Role for early-differentiated natural killer cells in infectious mononucleosis.

Science.gov (United States)

Azzi, Tarik; Lünemann, Anna; Murer, Anita; Ueda, Seigo; Béziat, Vivien; Malmberg, Karl-Johan; Staubli, Georg; Gysin, Claudine; Berger, Christoph; Münz, Christian; Chijioke, Obinna; Nadal, David

2014-10-16

A growing body of evidence suggests that the human natural killer (NK)-cell compartment is phenotypically and functionally heterogeneous and is composed of several differentiation stages. Moreover, NK-cell subsets have been shown to exhibit adaptive immune features during herpes virus infection in experimental mice and to expand preferentially during viral infections in humans. However, both phenotype and role of NK cells during acute symptomatic Epstein-Barr virus (EBV) infection, termed infectious mononucleosis (IM), remain unclear. Here, we longitudinally assessed the kinetics, the differentiation, and the proliferation of subsets of NK cells in pediatric IM patients. Our results indicate that acute IM is characterized by the preferential proliferation of early-differentiated CD56(dim) NKG2A(+) immunoglobulin-like receptor(-) NK cells. Moreover, this NK-cell subset exhibits features of terminal differentiation and persists at higher frequency during at least the first 6 months after acute IM. Finally, we demonstrate that this NK-cell subset preferentially degranulates and proliferates on exposure to EBV-infected B cells expressing lytic antigens. Thus, early-differentiated NK cells might play a key role in the immune control of primary infection with this persistent tumor-associated virus. © 2014 by The American Society of Hematology.

SOLAR ULTRAVIOLET EXPOSURE AND MORTALITY FROM SKIN TUMORS

Science.gov (United States)

Berwick, Marianne; Pestak, Claire; Thomas, Nancy

2015-01-01

Solar UV radiation (UVR) exposure is clearly associated with increased mortality from nonmelanoma skin cancer—usually squamous cell carcinoma. However, the association with cutaneous melanoma is unclear from the evidence in ecologic studies and several analytic studies have conflicting results regarding the effect of high levels of intermittent UV exposure prior to diagnosis on mortality. Understanding this conundrum is critical to present coherent public health messages and to improve the mortality rates from melanoma. PMID:25207375

Ergonomics and Beyond: Understanding How Chemical and Heat Exposures and Physical Exertions at Work Affect Functional Ability, Injury, and Long-Term Health.

Science.gov (United States)

Ross, Jennifer A; Shipp, Eva M; Trueblood, Amber B; Bhattacharya, Amit

2016-08-01

To honor Tom Waters's work on emerging occupational health issues, we review the literature on physical along with chemical exposures and their impact on functional outcomes. Many occupations present the opportunity for exposure to multiple hazardous exposures, including both physical and chemical factors. However, little is known about how these different factors affect functional ability and injury. The goal of this review is to examine the relationships between these exposures, impairment of the neuromuscular and musculoskeletal systems, functional outcomes, and health problems with a focus on acute injury. Literature was identified using online databases, including PubMed, Ovid Medline, and Google Scholar. References from included articles were searched for additional relevant articles. This review documented the limited existing literature that discussed cognitive impairment and functional disorders via neurotoxicity for physical exposures (heat and repetitive loading) and chemical exposures (pesticides, volatile organic compounds [VOCs], and heavy metals). This review supports that workers are exposed to physical and chemical exposures that are associated with negative health effects, including functional impairment and injury. Innovation in exposure assessment with respect to quantifying the joint exposure to these different exposures is especially needed for developing risk assessment models and, ultimately, preventive measures. Along with physical exposures, chemical exposures need to be considered, alone and in combination, in assessing functional ability and occupationally related injuries. © 2016, Human Factors and Ergonomics Society.

Differential reconstructed gene interaction networks for deriving toxicity threshold in chemical risk assessment.

Science.gov (United States)

Yang, Yi; Maxwell, Andrew; Zhang, Xiaowei; Wang, Nan; Perkins, Edward J; Zhang, Chaoyang; Gong, Ping

2013-01-01

Pathway alterations reflected as changes in gene expression regulation and gene interaction can result from cellular exposure to toxicants. Such information is often used to elucidate toxicological modes of action. From a risk assessment perspective, alterations in biological pathways are a rich resource for setting toxicant thresholds, which may be more sensitive and mechanism-informed than traditional toxicity endpoints. Here we developed a novel differential networks (DNs) approach to connect pathway perturbation with toxicity threshold setting. Our DNs approach consists of 6 steps: time-series gene expression data collection, identification of altered genes, gene interaction network reconstruction, differential edge inference, mapping of genes with differential edges to pathways, and establishment of causal relationships between chemical concentration and perturbed pathways. A one-sample Gaussian process model and a linear regression model were used to identify genes that exhibited significant profile changes across an entire time course and between treatments, respectively. Interaction networks of differentially expressed (DE) genes were reconstructed for different treatments using a state space model and then compared to infer differential edges/interactions. DE genes possessing differential edges were mapped to biological pathways in databases such as KEGG pathways. Using the DNs approach, we analyzed a time-series Escherichia coli live cell gene expression dataset consisting of 4 treatments (control, 10, 100, 1000 mg/L naphthenic acids, NAs) and 18 time points. Through comparison of reconstructed networks and construction of differential networks, 80 genes were identified as DE genes with a significant number of differential edges, and 22 KEGG pathways were altered in a concentration-dependent manner. Some of these pathways were perturbed to a degree as high as 70% even at the lowest exposure concentration, implying a high sensitivity of our DNs approach

Toxicological analysis of limonene reaction products using an in vitro exposure system

Science.gov (United States)

Anderson, Stacey E.; Khurshid, Shahana S.; Meade, B. Jean; Lukomska, Ewa; Wells, J.R.

2015-01-01

Epidemiological investigations suggest a link between exposure to indoor air chemicals and adverse health effects. Consumer products contain reactive chemicals which can form secondary pollutants which may contribute to these effects. The reaction of limonene and ozone is a well characterized example of this type of indoor air chemistry. The studies described here characterize an in vitro model using an epithelial cell line (A549) or differentiated epithelial tissue (MucilAir™). The model is used to investigate adverse effects following exposure to combinations of limonene and ozone. In A549 cells, exposure to both the parent compounds and reaction products resulted in alterations in inflammatory cytokine production. A one hour exposure to limonene + ozone resulted in decreased proliferation when compared to cells exposed to limonene alone. Repeated dose exposures of limonene or limonene + ozone were conducted on MucilAir™ tissue. No change in proliferation was observed but increases in cytokine production were observed for both the parent compounds and reaction products. Factors such as exposure duration, chemical concentration, and sampling time point were identified to influence result outcome. These findings suggest that exposure to reaction products may produce more severe effects compared to the parent compound. PMID:23220291

Rethinking Pedagogy for Second-Order Differential Equations: A Simplified Approach to Understanding Well-Posed Problems

Science.gov (United States)

Tisdell, Christopher C.

2017-01-01

Knowing an equation has a unique solution is important from both a modelling and theoretical point of view. For over 70 years, the approach to learning and teaching "well posedness" of initial value problems (IVPs) for second- and higher-order ordinary differential equations has involved transforming the problem and its analysis to a…

Perfluorooctane sulfonate induces neuronal and oligodendrocytic differentiation in neural stem cells and alters the expression of PPARγ in vitro and in vivo

International Nuclear Information System (INIS)

Wan Ibrahim, Wan Norhamidah; Tofighi, Roshan; Onishchenko, Natalia; Rebellato, Paola; Bose, Raj; Uhlén, Per; Ceccatelli, Sandra

2013-01-01

Perfluorinated compounds are ubiquitous chemicals of major concern for their potential adverse effects on the human population. We have used primary rat embryonic neural stem cells (NSCs) to study the effects of perfluorooctane sulfonate (PFOS) on the process of NSC spontaneous differentiation. Upon removal of basic fibroblast growth factor, NSCs were exposed to nanomolar concentrations of PFOS for 48 h, and then allowed to differentiate for additional 5 days. Exposure to 25 or 50 nM concentration resulted in a lower number of proliferating cells and a higher number of neurite-bearing TuJ1-positive cells, indicating an increase in neuronal differentiation. Exposure to 50 nM also significantly increased the number of CNPase-positive cells, pointing to facilitation of oligodendrocytic differentiation. PPAR genes have been shown to be involved in PFOS toxicity. By q-PCR we detected an upregulation of PPARγ with no changes in PPARα or PPARδ genes. One of the downstream targets of PPARs, the mitochondrial uncoupling protein 2 (UCP2) was also upregulated. The number of TuJ1- and CNPase-positive cells increased after exposure to PPARγ agonist rosiglitazone (RGZ, 3 μM) and decreased after pre-incubation with the PPARγ antagonist GW9662 (5 μM). RGZ also upregulated the expression of PPARγ and UCP2 genes. Meanwhile GW9662 abolished the UCP2 upregulation and decreased Ca 2+ activity induced by PFOS. Interestingly, a significantly higher expression of PPARγ and UCP3 genes was also detected in mouse neonatal brain after prenatal exposure to PFOS. These data suggest that PPARγ plays a role in the alteration of spontaneous differentiation of NSCs induced by nanomolar concentrations of PFOS. - Highlights: • PFOS decreases proliferation of neural stem cells (NSCs). • PFOS induces neuronal and oligodendrocytic differentiation in NSCs. • PFOS alters expression of PPARγ and UCP2 in vitro. • PFOS alters expression of PPARγ and UCP3 in vivo. • Block of PPARγ by

Perfluorooctane sulfonate induces neuronal and oligodendrocytic differentiation in neural stem cells and alters the expression of PPARγ in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Wan Ibrahim, Wan Norhamidah, E-mail: hamidah@science.upm.edu.my [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Tofighi, Roshan, E-mail: Roshan.Tofighi@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Onishchenko, Natalia, E-mail: Natalia.Onishchenko@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Rebellato, Paola, E-mail: Paola.Rebellato@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm (Sweden); Bose, Raj, E-mail: Raj.Bose@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Uhlén, Per, E-mail: Per.Uhlen@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm (Sweden); Ceccatelli, Sandra, E-mail: Sandra.Ceccatelli@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden)

2013-05-15

Perfluorinated compounds are ubiquitous chemicals of major concern for their potential adverse effects on the human population. We have used primary rat embryonic neural stem cells (NSCs) to study the effects of perfluorooctane sulfonate (PFOS) on the process of NSC spontaneous differentiation. Upon removal of basic fibroblast growth factor, NSCs were exposed to nanomolar concentrations of PFOS for 48 h, and then allowed to differentiate for additional 5 days. Exposure to 25 or 50 nM concentration resulted in a lower number of proliferating cells and a higher number of neurite-bearing TuJ1-positive cells, indicating an increase in neuronal differentiation. Exposure to 50 nM also significantly increased the number of CNPase-positive cells, pointing to facilitation of oligodendrocytic differentiation. PPAR genes have been shown to be involved in PFOS toxicity. By q-PCR we detected an upregulation of PPARγ with no changes in PPARα or PPARδ genes. One of the downstream targets of PPARs, the mitochondrial uncoupling protein 2 (UCP2) was also upregulated. The number of TuJ1- and CNPase-positive cells increased after exposure to PPARγ agonist rosiglitazone (RGZ, 3 μM) and decreased after pre-incubation with the PPARγ antagonist GW9662 (5 μM). RGZ also upregulated the expression of PPARγ and UCP2 genes. Meanwhile GW9662 abolished the UCP2 upregulation and decreased Ca{sup 2+} activity induced by PFOS. Interestingly, a significantly higher expression of PPARγ and UCP3 genes was also detected in mouse neonatal brain after prenatal exposure to PFOS. These data suggest that PPARγ plays a role in the alteration of spontaneous differentiation of NSCs induced by nanomolar concentrations of PFOS. - Highlights: • PFOS decreases proliferation of neural stem cells (NSCs). • PFOS induces neuronal and oligodendrocytic differentiation in NSCs. • PFOS alters expression of PPARγ and UCP2 in vitro. • PFOS alters expression of PPARγ and UCP3 in vivo. • Block of PPAR�

ELF-MF exposure affects the robustness of epigenetic programming during granulopoiesis

Science.gov (United States)

Manser, Melissa; Sater, Mohamad R. Abdul; Schmid, Christoph D.; Noreen, Faiza; Murbach, Manuel; Kuster, Niels; Schuermann, David; Schär, Primo

2017-03-01

Extremely-low-frequency magnetic fields (ELF-MF) have been classified as “possibly carcinogenic” to humans on the grounds of an epidemiological association of ELF-MF exposure with an increased risk of childhood leukaemia. Yet, underlying mechanisms have remained obscure. Genome instability seems an unlikely reason as the energy transmitted by ELF-MF is too low to damage DNA and induce cancer-promoting mutations. ELF-MF, however, may perturb the epigenetic code of genomes, which is well-known to be sensitive to environmental conditions and generally deranged in cancers, including leukaemia. We examined the potential of ELF-MF to influence key epigenetic modifications in leukaemic Jurkat cells and in human CD34+ haematopoietic stem cells undergoing in vitro differentiation into the neutrophilic lineage. During granulopoiesis, sensitive genome-wide profiling of multiple replicate experiments did not reveal any statistically significant, ELF-MF-dependent alterations in the patterns of active (H3K4me2) and repressive (H3K27me3) histone marks nor in DNA methylation. However, ELF-MF exposure showed consistent effects on the reproducibility of these histone and DNA modification profiles (replicate variability), which appear to be of a stochastic nature but show preferences for the genomic context. The data indicate that ELF-MF exposure stabilizes active chromatin, particularly during the transition from a repressive to an active state during cell differentiation.

Early endocrine disruptors exposure acts on 3T3-L1 differentiation and endocrine activity

Directory of Open Access Journals (Sweden)

Sofiane Boudalia

2017-06-01

Conclusion: This study confirms that EDs singularly or in mixtures, introduced during early stages of life, could affect the differentiation and the endocrine activity of adipocytes, and can act as potential factors for obesity.

Endogenous anticancer mechanism: differentiation.

Science.gov (United States)

Werneck, Miriam Bianchi de Frontin

2012-06-01

It has been recently shown that within heterogeneous tumor masses a small population of less differentiated transformed cells has the ability to self-renew and regenerate the bulk of the tumor. Their similarities with normal stem cells in terms of gene expression patterns, proliferative capacity and surface markers rendered them the name of cancer stem-like cells (CSC), and these are thought to be the tumor initiating cells (TIC). Their limited susceptibility to classical anti-tumor therapy help explain the high incidence of cancer-treatment relapses observed in selected malignancies. Much effort is being directed towards the understanding of factors that maintain CSC survival and their self-renewal capacity, with the goal that these same signaling pathways can be harnessed for treatments that aim at inducing CSC differentiation. This review will discuss the CSC theory, its implications, potential signaling pathways responsible for maintaining their undifferentiated and pluripotent states, and new venues being explored to target these cells in modern cancer therapy.

Health impact assessment of air pollution using a dynamic exposure profile: Implications for exposure and health impact estimates

International Nuclear Information System (INIS)

Dhondt, Stijn; Beckx, Carolien; Degraeuwe, Bart; Lefebvre, Wouter; Kochan, Bruno; Bellemans, Tom; Int Panis, Luc; Macharis, Cathy; Putman, Koen

2012-01-01

In both ambient air pollution epidemiology and health impact assessment an accurate assessment of the population exposure is crucial. Although considerable advances have been made in assessing human exposure outdoors, the assessments often do not consider the impact of individual travel behavior on such exposures. Population-based exposures to NO 2 and O 3 using only home addresses were compared with models that integrate all time-activity patterns—including time in commute—for Flanders and Brussels. The exposure estimates were used to estimate the air pollution impact on years of life lost due to respiratory mortality. Health impact of NO 2 using an exposure that integrates time-activity information was on average 1.2% higher than when assuming that people are always at their home address. For ozone the overall estimated health impact was 0.8% lower. Local differences could be much larger, with estimates that differ up to 12% from the exposure using residential addresses only. Depending on age and gender, deviations from the population average were seen. Our results showed modest differences on a regional level. At the local level, however, time-activity patterns indicated larger differences in exposure and health impact estimates, mainly for people living in more rural areas. These results suggest that for local analyses the dynamic approach can contribute to an improved assessment of the health impact of various types of pollution and to the understanding of exposure differences between population groups. - Highlights: ► Exposure to ambient air pollution was assessed integrating population mobility. ► This dynamic exposure was integrated into a health impact assessment. ► Differences between the dynamic and residential exposure were quantified. ► Modest differences in health impact were found at a regional level. ► At municipal level larger differences were found, influenced by gender and age.

Induction of apoptotic death and retardation of neuronal differentiation of human neural stem cells by sodium arsenite treatment

Energy Technology Data Exchange (ETDEWEB)

Ivanov, Vladimir N., E-mail: vni3@columbia.edu [Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, NY 10032 (United States); Hei, Tom K. [Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, NY 10032 (United States)

2013-04-01

Chronic arsenic toxicity is a global health problem that affects more than 100 million people worldwide. Long-term health effects of inorganic sodium arsenite in drinking water may result in skin, lung and liver cancers and in severe neurological abnormalities. We investigated in the present study whether sodium arsenite affects signaling pathways that control cell survival, proliferation and neuronal differentiation of human neural stem cells (NSC). We demonstrated that the critical signaling pathway, which was suppressed by sodium arsenite in NSC, was the protective PI3K–AKT pathway. Sodium arsenite (2–4 μM) also caused down-regulation of Nanog, one of the key transcription factors that control pluripotency and self-renewal of stem cells. Mitochondrial damage and cytochrome-c release induced by sodium arsenite exposure was followed by initiation of the mitochondrial apoptotic pathway in NSC. Beside caspase-9 and caspase-3 inhibitors, suppression of JNK activity decreased levels of arsenite-induced apoptosis in NSC. Neuronal differentiation of NSC was substantially inhibited by sodium arsenite exposure. Overactivation of JNK1 and ERK1/2 and down-regulation of PI3K–AKT activity induced by sodium arsenite were critical factors that strongly affected neuronal differentiation. In conclusion, sodium arsenite exposure of human NSC induces the mitochondrial apoptotic pathway, which is substantially accelerated due to the simultaneous suppression of PI3K–AKT. Sodium arsenite also negatively affects neuronal differentiation of NSC through overactivation of MEK–ERK and suppression of PI3K–AKT. - Highlights: ► Arsenite induces the mitochondrial apoptotic pathway in human neural stem cells. ► Arsenite-induced apoptosis is strongly upregulated by suppression of PI3K–AKT. ► Arsenite-induced apoptosis is strongly down-regulated by inhibition of JNK–cJun. ► Arsenite negatively affects neuronal differentiation by inhibition of PI3K–AKT.

Induction of apoptotic death and retardation of neuronal differentiation of human neural stem cells by sodium arsenite treatment

International Nuclear Information System (INIS)

Ivanov, Vladimir N.; Hei, Tom K.

2013-01-01

Chronic arsenic toxicity is a global health problem that affects more than 100 million people worldwide. Long-term health effects of inorganic sodium arsenite in drinking water may result in skin, lung and liver cancers and in severe neurological abnormalities. We investigated in the present study whether sodium arsenite affects signaling pathways that control cell survival, proliferation and neuronal differentiation of human neural stem cells (NSC). We demonstrated that the critical signaling pathway, which was suppressed by sodium arsenite in NSC, was the protective PI3K–AKT pathway. Sodium arsenite (2–4 μM) also caused down-regulation of Nanog, one of the key transcription factors that control pluripotency and self-renewal of stem cells. Mitochondrial damage and cytochrome-c release induced by sodium arsenite exposure was followed by initiation of the mitochondrial apoptotic pathway in NSC. Beside caspase-9 and caspase-3 inhibitors, suppression of JNK activity decreased levels of arsenite-induced apoptosis in NSC. Neuronal differentiation of NSC was substantially inhibited by sodium arsenite exposure. Overactivation of JNK1 and ERK1/2 and down-regulation of PI3K–AKT activity induced by sodium arsenite were critical factors that strongly affected neuronal differentiation. In conclusion, sodium arsenite exposure of human NSC induces the mitochondrial apoptotic pathway, which is substantially accelerated due to the simultaneous suppression of PI3K–AKT. Sodium arsenite also negatively affects neuronal differentiation of NSC through overactivation of MEK–ERK and suppression of PI3K–AKT. - Highlights: ► Arsenite induces the mitochondrial apoptotic pathway in human neural stem cells. ► Arsenite-induced apoptosis is strongly upregulated by suppression of PI3K–AKT. ► Arsenite-induced apoptosis is strongly down-regulated by inhibition of JNK–cJun. ► Arsenite negatively affects neuronal differentiation by inhibition of PI3K–AKT

Differential modulation of ammonia excretion, Rhesus glycoproteins and ion-regulation in common carp (Cyprinus carpio) following individual and combined exposure to waterborne copper and ammonia.

Science.gov (United States)

Sinha, Amit Kumar; Kapotwe, Mumba; Dabi, Shambel Boki; Montes, Caroline da Silva; Shrivastava, Jyotsna; Blust, Ronny; De Boeck, Gudrun

2016-01-01

The main objective of this study was to understand the mode of interaction between waterborne copper (Cu) and high environmental ammonia (HEA) exposure on freshwater fish, and how they influence the toxicity of each other when present together. For this purpose, individual and combined effects of Cu and HEA were examined on selected physiological and ion-regulatory processes and changes at transcript level in the common carp (Cyprinus carpio). Juvenile carp were exposed to 2.6μM Cu (25% of the 96h LC50value) and to 0.65mM ammonia (25% of the 96h LC50value) singly and as a mixture for 12h, 24h, 48h, 84h and 180h. Responses such as ammonia (Jamm) and urea (Jurea) excretion rate, plasma ammonia and urea, plasma ions (Na(+), Cl(-) and K(+)), muscle water content (MWC) as well as branchial Na(+)/K(+)-ATPase (NKA) and H(+)-ATPase activity, and branchial mRNA expression of NKA, H(+)-ATPase, Na(+)/H(+) exchanger (NHE-3) and Rhesus (Rh) glycoproteins were investigated under experimental conditions. Results show that Jamm was inhibited during Cu exposure, while HEA exposed fish were able to increase excretion efficiently. In the combined exposure, Jamm remained at the control levels indicating that Cu and HEA abolished each other's effect. Expression of Rhcg (Rhcg-a and Rhcg-b) mRNA was upregulated during HEA, thereby facilitated ammonia efflux out of gills. On the contrary, Rhcg-a transcript level declined following Cu exposure which might account for Cu induced Jamm inhibition. Likewise, Rhcg-a was also down-regulated in Cu-HEA co-exposed fish whilst a temporary increment was noted for Rhch-b. Fish exposed to HEA displayed pronounced up-regulation in NKA expression and activity and stable plasma ion levels. In both the Cu exposure alone and combined Cu-HEA exposure, ion-osmo homeostasis was adversely affected, exemplified by the significant reduction in plasma [Na(+)] and [Cl(-)], and elevated plasma [K(+)], along with an elevation in MWC. These changes were accompanied

Exposure to sub-concussive head injury in boxing and other sports.

Science.gov (United States)

Erlanger, David M

2015-01-01

Current characterizations of chronic traumatic brain injury (CTBI) in boxing, football and other sports are reviewed in the context of the history of research on sub-concussive brain trauma in athletes. The utility of exposure models for understanding CTBI in boxers is examined and concerns regarding the paucity of findings supportive of an exposure model for CTBI in football players are discussed. Recommendations for development of exposure models for sport-specific phenotypic characterizations of CTBI are presented.

Structural and functional localization of airway effects from episodic exposure of infant monkeys to allergen and/or ozone

International Nuclear Information System (INIS)

Joad, Jesse P.; Kott, Kayleen S.; Bric, John M.; Peake, Janice L.; Plopper, Charles G.; Schelegle, Edward S.; Gershwin, Laurel J.; Pinkerton, Kent E.

2006-01-01

Both allergen and ozone exposure increase asthma symptoms and airway responsiveness in children. Little is known about how these inhalants may differentially modify airway responsiveness in large proximal as compared to small distal airways. We evaluated whether bronchi and respiratory bronchioles from infant monkeys exposed episodically to allergen and/or ozone differentially develop intrinsic hyperresponsiveness to methacholine and whether eosinophils and/or pulmonary neuroendocrine cells play a role. Infant monkeys were exposed episodically for 5 months to: (1) filtered air, (2) aerosolized house dust mite allergen, (3) ozone 0.5 ppm, or (4) house dust mite allergen + ozone. Studying the function/structure relationship of the same lung slices, we evaluated methacholine airway responsiveness and histology of bronchi and respiratory bronchioles. In bronchi, intrinsic responsiveness was increased by allergen exposure, an effect reduced by bombesin antagonist. In respiratory bronchioles, intrinsic airway responsiveness was increased by allergen + ozone exposure. Eosinophils were increased by allergen and allergen + ozone exposure in bronchi and by allergen exposure in respiratory bronchioles. In both airways, exposure to allergen + ozone resulted in fewer tissue eosinophils than did allergen exposure alone. In bronchi, but not in respiratory bronchioles, the number of eosinophils and neuroendocrine cells correlated with airway responsiveness. We conclude that episodically exposing infant monkeys to house dust mite allergen with or without ozone increased intrinsic airway responsiveness to methacholine in bronchi differently than in respiratory bronchioles. In bronchi, eosinophils and neuroendocrine cells may play a role in the development of airway hyperresponsiveness

Biophysical Regulation of Vascular Differentiation and Assembly

CERN Document Server

Gerecht, Sharon

2011-01-01

The ability to grow stem cells in the laboratory and to guide their maturation to functional cells allows us to study the underlying mechanisms that govern vasculature differentiation and assembly in health and disease. Accumulating evidence suggests that early stages of vascular growth are exquisitely tuned by biophysical cues from the microenvironment, yet the scientific understanding of such cellular environments is still in its infancy. Comprehending these processes sufficiently to manipulate them would pave the way to controlling blood vessel growth in therapeutic applications. This book assembles the works and views of experts from various disciplines to provide a unique perspective on how different aspects of its microenvironment regulate the differentiation and assembly of the vasculature. In particular, it describes recent efforts to exploit modern engineering techniques to study and manipulate various biophysical cues. Biophysical Regulation of Vascular Differentiation and Assembly provides an inter...

Lead induces similar gene expression changes in brains of gestationally exposed adult mice and in neurons differentiated from mouse embryonic stem cells.

Directory of Open Access Journals (Sweden)

Francisco Javier Sánchez-Martín

Full Text Available Exposure to environmental toxicants during embryonic life causes changes in the expression of developmental genes that may last for a lifetime and adversely affect the exposed individual. Developmental exposure to lead (Pb, an ubiquitous environmental contaminant, causes deficits in cognitive functions and IQ, behavioral effects, and attention deficit hyperactivity disorder (ADHD. Long-term effects observed after early life exposure to Pb include reduction of gray matter, alteration of myelin structure, and increment of criminal behavior in adults. Despite growing research interest, the molecular mechanisms responsible for the effects of lead in the central nervous system are still largely unknown. To study the molecular changes due to Pb exposure during neurodevelopment, we exposed mice to Pb in utero and examined the expression of neural markers, neurotrophins, transcription factors and glutamate-related genes in hippocampus, cortex, and thalamus at postnatal day 60. We found that hippocampus was the area where gene expression changes due to Pb exposure were more pronounced. To recapitulate gestational Pb exposure in vitro, we differentiated mouse embryonic stem cells (ESC into neurons and treated ESC-derived neurons with Pb for the length of the differentiation process. These neurons expressed the characteristic neuronal markers Tubb3, Syp, Gap43, Hud, Ngn1, Vglut1 (a marker of glutamatergic neurons, and all the glutamate receptor subunits, but not the glial marker Gafp. Importantly, several of the changes observed in Pb-exposed mouse brains in vivo were also observed in Pb-treated ESC-derived neurons, including those affecting expression of Ngn1, Bdnf exon IV, Grin1, Grin2D, Grik5, Gria4, and Grm6. We conclude that our ESC-derived model of toxicant exposure during neural differentiation promises to be a useful model to analyze mechanisms of neurotoxicity induced by Pb and other environmental agents.

Mialgias: Approaches to differential diagnosis, treatment

Directory of Open Access Journals (Sweden)

Nadezhda Aleksandrovna Shostak

2013-01-01

Full Text Available Differential diagnosis in muscle pains often presents great difficulties so all existing signs of the disease should be carefully considered to make its diagnosis and to prescribe adequate therapy. The paper considers the causes of muscle pains, laboratory and instrumental studies (immunological tests, determination of the level of specific muscular enzymes, primarily creatine phosphokinase – CPK, etc., and the main reasons for enhanced plasma CPK activity. It also describes acute and chronic mialgias associated with enhanced plasma CPK activity, as well as diseases in which mialgias are related to the normal level of CPK, myofascial syndrome (MFS and fibromyalgia (FM in particular. The characteristic features of MFS are given in its diagnostic criteria. It is stated that a differential diagnosis should be made between MFS and major muscle pain-associated abnormalities, such as polymyalgia rheumatica, FM, etc. Diagnosticcriteria for polymyalgia rheumatica are given. A MFS treatment algorithm is presented. Local exposure methods applied to altered musculoligamentous structures in combination with myorelaxants and non-steroidal anti-inflammatory drugs assume paramount importance in MFS.

Population-based nutrikinetic modeling of polyphenol exposure

NARCIS (Netherlands)

van Velzen, E.J.J.; Westerhuis, J.A.; Grün, C.H.; Jacobs, D.M.; Eilers, P.H.C.; Mulder, Th.P.; Foltz, M.; Garczarek, U.; Kemperman, R.; Vaughan, E. E.; van Duynhoven, J.P.M.; Smilde, A.K.

2014-01-01

The beneficial health effects of fruits and vegetables have been attributed to their polyphenol content. These compounds undergo many bioconversions in the body. Modeling polyphenol exposure of humans upon intake is a prerequisite for understanding the modulating effect of the food matrix and the

Population-based nutrikinetic modelling of phytochemical exposure

NARCIS (Netherlands)

Velzen, van E.J.J.; Westerhuis, J.A.; Grün, C.H.; Duynhoven, van J.P.M.; Jacobs, D.M.; Eilers, P.H.C.; Mulder, T.P.; Foltz, M.; Garczarek, U.; Kemperman, R.; Vaughan, E.E.; Smilde, A.K.

2014-01-01

The beneficial health effects of fruits and vegetables have been attributed to their polyphenol content. These compounds undergo many bioconversions in the body. Modeling polyphenol exposure of humans upon intake is a prerequisite for understanding the modulating effect of the food matrix and the

Introduction to partial differential equations

CERN Document Server

Borthwick, David

2016-01-01

This modern take on partial differential equations does not require knowledge beyond vector calculus and linear algebra. The author focuses on the most important classical partial differential equations, including conservation equations and their characteristics, the wave equation, the heat equation, function spaces, and Fourier series, drawing on tools from analysis only as they arise.Within each section the author creates a narrative that answers the five questions: (1) What is the scientific problem we are trying to understand? (2) How do we model that with PDE? (3) What techniques can we use to analyze the PDE? (4) How do those techniques apply to this equation? (5) What information or insight did we obtain by developing and analyzing the PDE? The text stresses the interplay between modeling and mathematical analysis, providing a thorough source of problems and an inspiration for the development of methods.

Tensor and vector analysis with applications to differential geometry

CERN Document Server

Springer, C E

2012-01-01

Concise and user-friendly, this college-level text assumes only a knowledge of basic calculus in its elementary and gradual development of tensor theory. The introductory approach bridges the gap between mere manipulation and a genuine understanding of an important aspect of both pure and applied mathematics.Beginning with a consideration of coordinate transformations and mappings, the treatment examines loci in three-space, transformation of coordinates in space and differentiation, tensor algebra and analysis, and vector analysis and algebra. Additional topics include differentiation of vect

Human exposure to unconventional natural gas development: A public health demonstration of periodic high exposure to chemical mixtures in ambient air.

Science.gov (United States)

Brown, David R; Lewis, Celia; Weinberger, Beth I

2015-01-01

hydraulic fracturing stage. Over one year, compressor station emissions created 118 peak exposure levels and a gas processing plant produced 99 peak exposures over one year. The screening model identified the periods during the day and the specific weather conditions when the highest potential exposures would occur. The periodicity of occurrence of extreme exposures is similar to the episodic nature of the health complaints reported in Washington County and in the literature. This study demonstrates the need to determine the aggregate quantitative impact on health when multiple facilities are placed near residences, schools, daycare centers and other locations where people are present. It shows that understanding the influence of air stability and wind direction is essential to exposure assessment at the residential level. The model can be applied to other emissions and similar sites. Profiles such as this will assist health providers in understanding the frequency and intensity of the human exposures when diagnosing and treating patients living near unconventional natural gas development.

Differential Effects of Methyl-4-Phenylpyridinium Ion, Rotenone, and Paraquat on Differentiated SH-SY5Y Cells

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João Barbosa Martins

2013-01-01

Full Text Available Paraquat (PQ, a cationic nonselective bipyridyl herbicide, has been used as neurotoxicant to modulate Parkinson’s disease in laboratory settings. Other compounds like rotenone (ROT, a pesticide, and 1-methyl-4-phenylpyridinium ion (MPP+ have been widely used as neurotoxicants. We compared the toxicity of these three neurotoxicants using differentiated dopaminergic SH-SY5Y human cells, aiming to elucidate their differential effects. PQ-induced neurotoxicity was shown to be concentration and time dependent, being mitochondrial dysfunction followed by neuronal death. On the other hand, cells exposure to MPP+ induced mitochondrial dysfunction, but not cellular lyses. Meanwhile, ROT promoted both mitochondrial dysfunction and neuronal death, revealing a biphasic pattern. To further elucidate PQ neurotoxic mechanism, several protective agents were used. SH-SY5Y cells pretreatment with tiron (TIR and 2-hydroxybenzoic acid sodium salt (NaSAL, both antioxidants, and Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, a nitric oxide synthase inhibitor, partially protected against PQ-induced cell injury. Additionally, 1-(2-[bis(4-fluorophenylmethoxy]ethyl-4-(3-phenyl-propylpiperazine (GBR 12909, a dopamine transporter inhibitor, and cycloheximide (CHX, a protein synthesis inhibitor, also partially protected against PQ-induced cell injury. In conclusion, we demonstrated that PQ, MPP+, and ROT exerted differential toxic effects on dopaminergic cells. PQ neurotoxicity occurred through exacerbated oxidative stress, with involvement of uptake through the dopamine transporter and protein synthesis.

Exposure of the mouse perinatal testis to radiation leads to hypospermia at sexual maturity

International Nuclear Information System (INIS)

Forand, A.; Messiaen, S.; Habert, R.; Bernardino-Sgherri, J.

2009-01-01

The first round of mouse spermatogenesis begins from 3 to 4 days after birth through differentiation of gonocytes into spermatogonial-stem cells and type A spermatogonia. Consequently, this step of differentiation may determine generation of the original population of stem cells and the fertility potential of the adult mouse. We aimed to determine the effect of perinatal exposure to ionizing radiation on the testis at the end of the first wave of spermatogenesis and at sexual maturity. Our results show that, radiation sensitivity of the testis substantially decreases from late foetal life to the end of the first week after birth. In addition, partial or full recovery from radiation induced testicular weight loss occurred between the first round of spermatogenesis and sexual maturity, and this was associated with the stimulation of spermatogonial proliferation. Exposure of mice at 17.5 days after conception or at 1 day after birth to γ-rays decreased the sperm counts at sexual maturity, while exposure of 8 day-old mice had no effect. This suggests that irradiation of late foetal or early neonatal testes has a direct impact on the generation of the neonatal spermatogonial-stem cell pool. (authors)

Low-dose/dose-rate γ radiation depresses neural differentiation and alters protein expression profiles in neuroblastoma SH-SY5Y cells and C17.2 neural stem cells.

Science.gov (United States)

Bajinskis, Ainars; Lindegren, Heléne; Johansson, Lotta; Harms-Ringdahl, Mats; Forsby, Anna

2011-02-01

The effects of low doses of ionizing radiation on cellular development in the nervous system are presently unclear. The focus of the present study was to examine low-dose γ-radiation-induced effects on the differentiation of neuronal cells and on the development of neural stem cells to glial cells. Human neuroblastoma SH-SY5Y cells were exposed to (137)Cs γ rays at different stages of retinoic acid-induced neuronal differentiation, and neurite formation was determined 6 days after exposure. When SH-SY5Y cells were exposed to low-dose-rate γ rays at the onset of differentiation, the number of neurites formed per cell was significantly less after exposure to either 10, 30 or 100 mGy compared to control cells. Exposure to 10 and 30 mGy attenuated differentiation of immature C17.2 mouse-derived neural stem cells to glial cells, as verified by the diminished expression of glial fibrillary acidic protein. Proteomic analysis of the neuroblastoma cells by 2D-PAGE after 30 mGy irradiation showed that proteins involved in neuronal development were downregulated. Proteins involved in cell cycle and proliferation were altered in both cell lines after exposure to 30 mGy; however, the rate of cell proliferation was not affected in the low-dose range. The radiation-induced attenuation of differentiation and the persistent changes in protein expression is indicative of an epigenetic rather than a cytotoxic mechanism.

Understand electrical and electronics maths

CERN Document Server

Bishop, Owen

1993-01-01

Understand Electrical and Electronics Maths covers elementary maths and the aspects of electronics. The book discusses basic maths including quotients, algebraic fractions, logarithms, types of equations and balancing of equations. The text also describes the main features and functions of graphs and the solutions to simpler types of electronics problems. The book then tackles the applications of polar coordinates in electronics, limits, differentiation and integration, and the applications of maths of rates of change in electronics. The activities of an electronic circuit; techniques of math

Skin exposure to isocyanates: reasons for concern.

Science.gov (United States)

Bello, Dhimiter; Herrick, Christina A; Smith, Thomas J; Woskie, Susan R; Streicher, Robert P; Cullen, Mark R; Liu, Youcheng; Redlich, Carrie A

2007-03-01

Isocyanates (di- and poly-), important chemicals used worldwide to produce polyurethane products, are a leading cause of occupational asthma. Respiratory exposures have been reduced through improved hygiene controls and the use of less-volatile isocyanates. Yet isocyanate asthma continues to occur, not uncommonly in settings with minimal inhalation exposure but opportunity for skin exposure. In this review we evaluate the potential role of skin exposure in the development of isocyanate asthma. We reviewed the published animal and human literature on isocyanate skin-exposure methods, workplace skin exposure, skin absorption, and the role of skin exposure in isocyanate sensitization and asthma. We selected relevant articles from computerized searches on Medline, U.S. Environmental Protection Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, and Google databases using the keywords "isocyanate," "asthma," "skin," "sensitization," and other synonymous terms, and our own extensive collection of isocyanate publications. Isocyanate production and use continues to increase as the polyurethane industry expands. There is substantial opportunity for isocyanate skin exposure in many work settings, but such exposure is challenging to quantify and continues to be underappreciated. Isocyanate skin exposure can occur at work, even with the use of personal protective equipment, and may also occur with consumer use of certain isocyanate products. In animals, isocyanate skin exposure is an efficient route to induce sensitization, with subsequent inhalation challenge resulting in asthma-like responses. Several lines of evidence support a similar role for human isocyanate skin exposure, namely, that such exposure occurs and can contribute to the development of isocyanate asthma in certain settings, presumably by inducing systemic sensitization. Integrated animal and human research is needed to better understand the role of skin

An Investigation of Organic and Inorganic Mercury Exposure and Blood Pressure in a Small-Scale Gold Mining Community in Ghana

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Mozhgon Rajaee

2015-08-01

Full Text Available There is increasing concern about the cardiovascular effects of mercury (Hg exposure, and that organic methylmercury and inorganic Hg2+ may affect the cardiovascular system and blood pressure differentially. In small-scale gold mining communities where inorganic, elemental Hg exposures are high, little is known about the effects of Hg on blood pressure. In 2011, we assessed the relationship between Hg exposure and blood pressure (BP in a cross-sectional study of adults from a small-scale gold mining community, Kejetia, and subsistence farming community, Gorogo, in Ghana’s Upper East Region. Participants’ resting heart rate and BP were measured, and hair and urine samples were provided to serve as biomarkers of organic and inorganic Hg exposure, respectively. Participants included 70 miners and 26 non-miners from Kejetia and 75 non-miners from Gorogo. Total specific gravity-adjusted urinary and hair Hg was higher among Kejetia miners than Kejetia non-miners and Gorogo participants (median urinary Hg: 5.17, 1.18, and 0.154 µg/L, respectively; hair Hg: 0.945, 0.419, and 0.181 µg/g, respectively. Hypertension was prevalent in 17.7% of Kejetia and 21.3% of Gorogo participants. Urinary and hair Hg were not significantly associated with systolic or diastolic BP for Kejetia or Gorogo participants while adjusting for sex, age, and smoking status. Although our results follow trends seen in other studies, the associations were not of statistical significance. Given the unique study population and high exposures to inorganic Hg, the work contained here will help increase our understanding of the cardiovascular effects of Hg.

Differentiation between exposures to high or low ionizing radiation by means of Triage type analysis

International Nuclear Information System (INIS)

Guerrero C, C.; Arceo M, C.; Martinez A, J.; Cortina R, E.

2016-09-01

According to a culture of disaster prevention, in this case a radiological emergency, in which a large number of people are exposed to high doses of ionizing radiation, is necessary to make urgent decisions regarding the appropriate treatment, which for each case is required. In this regard, chromosomal analysis may provide additional information to that obtained from clinical observations confirming cases that suffered severe partial exposure and at the same time discriminating against false positives attributable to previous infections or hysterical behavior. The ionizing radiation causes different types of aberrations in the chromosomes, but one of the most characteristic is dicentric. The analysis of these in lymphocytes is a good indicator of the degree of exposure, because apart from being easily recognizable, the basal frequency in the population is low (1 x 10 3 cells) and increases in proportion to the dose. In order to establish the exposure dose, is usually necessary to analyze 1000 cells, a procedure that in an emergency, is very slow since is necessary to make rapid decisions to apply the appropriate treatment to the patient. The results of this intercalibration exercise demonstrate that the analysis of 20, 30 or 50 metaphases is sufficient to separate the cases of overexposure from the non-radio exposed ones and to the first ones by gravity category. (Author)

Suppression of autophagy by extracellular vesicles promotes myofibroblast differentiation in COPD pathogenesis

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Yu Fujita

2015-11-01

Full Text Available Extracellular vesicles (EVs, such as exosomes and microvesicles, encapsulate proteins and microRNAs (miRNAs as new modulators of both intercellular crosstalk and disease pathogenesis. The composition of EVs is modified by various triggers to maintain physiological homeostasis. In response to cigarette smoke exposure, the lungs develop emphysema, myofibroblast accumulation and airway remodelling, which contribute to chronic obstructive pulmonary disease (COPD. However, the lung disease pathogenesis through modified EVs in stress physiology is not understood. Here, we investigated an EV-mediated intercellular communication mechanism between primary human bronchial epithelial cells (HBECs and lung fibroblasts (LFs and discovered that cigarette smoke extract (CSE-induced HBEC-derived EVs promote myofibroblast differentiation in LFs. Thorough evaluations of the modified EVs and COPD lung samples showed that cigarette smoke induced relative upregulation of cellular and EV miR-210 expression of bronchial epithelial cells. Using co-culture assays, we showed that HBEC-derived EV miR-210 promotes myofibroblast differentiation in LFs. Surprisingly, we found that miR-210 directly regulates autophagy processes via targeting ATG7, and expression levels of miR-210 are inversely correlated with ATG7 expression in LFs. Importantly, autophagy induction was significantly decreased in LFs from COPD patients, and silencing ATG7 in LFs led to myofibroblast differentiation. These findings demonstrate that CSE triggers the modification of EV components and identify bronchial epithelial cell-derived miR-210 as a paracrine autophagy mediator of myofibroblast differentiation that has potential as a therapeutic target for COPD. Our findings show that stressor exposure changes EV compositions as emerging factors, potentially controlling pathological disorders such as airway remodelling in COPD.

Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.

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Xiaoke Ma

2015-06-01

Full Text Available Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules. We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.

Differential susceptibility of horizontal and vertical swimming activity to cadmium exposure in a gammaridean amphipod (Gammarus lawrencianus)

International Nuclear Information System (INIS)

Wallace, W.G.; Estephan, A.

2004-01-01

In this study two indices of swimming behavior (horizontal and vertical swimming activity) in a gammaridean amphipod (Gammarus lawrencianus) were examined for their sensitivity to Cd exposure. G. lawrencianus were exposed for 72 h to a variety of Cd concentrations [background (∼12), 62, 125, 250 and 500 μg l -1 ] at 20 ppt. Subsequent to exposure, video surveillance of survivors held within grooved rings or clear boxes was used to assess horizontal swimming activity (percentage of time mobile) and vertical swimming activity (number of surfacings), respectively. Results show that control amphipods were quite active, being mobile ∼61% of the time, with horizontal swimming activity decreasing (P -1 . Vertical swimming activity in amphipods was also impacted by Cd exposure (P -1 ) and 62 μg l -1 (60 versus ∼26 surfacings, respectively), which is approximately four-fold lower than the estimated 72 h LC 50 (250 μg l -1 ) for G. lawrencianus. Based on fluid dynamic considerations, it is speculated that of the two behaviors, vertical swimming activity is more sensitive to Cd exposure because of the presumed greater energetic costs associated with producing enough thrust to attain the lift required to make a vertical ascent into the water

Examining the association between exposure to mass media and health insurance enrolment in Ghana.

Science.gov (United States)

Kansanga, Moses Mosonsieyiri; Asumah Braimah, Joseph; Antabe, Roger; Sano, Yuji; Kyeremeh, Emmanuel; Luginaah, Isaac

2018-02-12

Although previous studies have explored the National Health Insurance Scheme (NHIS) in Ghana, very little attention is paid to the influence of mass media exposure on NHIS enrolment. Yet, understanding this linkage is important, particularly due to the critical role of mass media in disseminating health information and shaping people's health perceptions and choices. Using data from the 2014 Ghana Demographic and Health Survey, we employed logistic regression analysis to understand the relationship between NHIS enrolment and exposure to print media, radio, and television. Our findings indicate that women with more exposure to radio (OR = 1.23, P NHIS than those with no exposure. For men, more exposure to print media was associated with higher odds of enrolling in the NHIS (OR = 1.41, P NHIS enrolment in Ghana. However, given that the relationship between media exposure and enrolment in the NHIS was gendered, we recommend that policymakers should pay attention to these dynamics to ensure effective targeting in NHIS media campaigns for increased enrolment into the scheme. Copyright © 2018 John Wiley & Sons, Ltd.

Prepubertal Gynecomastia Due to Indirect Exposure to Nonformulary Bioidentical Hormonal Replacement Therapy: A Case Report.

Science.gov (United States)

De Pinho, Joao Correia; Aghajanova, Lusine; Herndon, Christopher N

2016-01-01

Gynecomastia is a disorder of the endocrine system characterized by an abnormal presence of a palpable unilateral or bilateral enlargement and proliferation of glandular ductal benign breast tissue in male individuals. This case discusses the medical implications of an unregulated, indirect exposure to nonformulary, bioidentical hormone replacement therapy in male children. An 8-year-old boy presented with prepubertal gynecomastia secondary to estrogen exposure from maternal use of bioidentical hormonal replacement therapy (the Wiley protocol). We review the literature on prepubertal gynecomastia secondary to exogenous estrogen exposure, evaluation, clinical surveillance of the pubertal development, and relevant short- and long-term implications. Indirect exposure to nonformulary hormonal replacement in our case report was an etiologic factor in the development of prepubertal gynecomastia. This novel estrogen exposure source has important implications in the differential diagnosis of prepubertal gynecomastia and potential adverse effects secondary to precocious hormonal exposure.

Stochastic Differential Equations and Kondratiev Spaces

Energy Technology Data Exchange (ETDEWEB)

Vaage, G.

1995-05-01

The purpose of this mathematical thesis was to improve the understanding of physical processes such as fluid flow in porous media. An example is oil flowing in a reservoir. In the first of five included papers, Hilbert space methods for elliptic boundary value problems are used to prove the existence and uniqueness of a large family of elliptic differential equations with additive noise without using the Hermite transform. The ideas are then extended to the multidimensional case and used to prove existence and uniqueness of solution of the Stokes equations with additive noise. The second paper uses functional analytic methods for partial differential equations and presents a general framework for proving existence and uniqueness of solutions to stochastic partial differential equations with multiplicative noise, for a large family of noises. The methods are applied to equations of elliptic, parabolic as well as hyperbolic type. The framework presented can be extended to the multidimensional case. The third paper shows how the ideas from the second paper can be extended to study the moving boundary value problem associated with the stochastic pressure equation. The fourth paper discusses a set of stochastic differential equations. The fifth paper studies the relationship between the two families of Kondratiev spaces used in the thesis. 102 refs.

NOV/CCN3 impairs muscle cell commitment and differentiation

International Nuclear Information System (INIS)

Calhabeu, Frederico; Lafont, Jerome; Le Dreau, Gwenvael; Laurent, Maryvonne; Kazazian, Chantal; Schaeffer, Laurent; Martinerie, Cecile; Dubois, Catherine

2006-01-01

NOV (nephroblastoma overexpressed) is a member of a family of proteins which encodes secreted matrix-associated proteins. NOV is expressed during development in dermomyotome and limb buds, but its functions are still poorly defined. In order to understand the role of NOV in myogenic differentiation, C2C12 cells overexpressing NOV (C2-NOV) were generated. These cells failed to engage into myogenic differentiation, whereas they retained the ability to differentiate into osteoblasts. In differentiating conditions, C2-NOV cells remained proliferative, failed to express differentiation markers and lost their ability to form myotubes. Inhibition of differentiation by NOV was also observed with human primary muscle cells. Further examination of C2-NOV cells revealed a strong downregulation of the myogenic determination genes MyoD and Myf5 and of IGF-II expression. MyoD forced expression in C2-NOV was sufficient to restore differentiation and IGF-II induction whereas 10 -6 M insulin treatment had no effects. NOV therefore acts upstream of MyoD and does not affect IGF-II induction and signaling. HES1, a target of Notch, previously proposed to mediate NOV action, was not implicated in the inhibition of differentiation. We propose that NOV is a specific cell fate regulator in the myogenic lineage, acting negatively on key myogenic genes thus controlling the transition from progenitor cells to myoblasts

Reconstructing human pancreatic differentiation by mapping specific cell populations during development

DEFF Research Database (Denmark)

Ramond, Cyrille; Glaser, Nicolas; Berthault, Claire

2017-01-01

. Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic......Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate...... cell types and how such lineage decisions are regulated....

Bridging Knowledge Gaps to Understand How Zika Virus Exposure and Infection Affect Child Development.

Science.gov (United States)

Kapogiannis, Bill G; Chakhtoura, Nahida; Hazra, Rohan; Spong, Catherine Y

2017-05-01

The Zika virus (ZIKV) epidemic has profoundly affected the lives of children and families across the Americas. As the number of children born with ZIKV-related complications continues to grow, the long-term developmental trajectory for these children and the effect on their families remains largely unknown. In September 2016, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and partner National Institutes of Health institutes convened a workshop to develop a research agenda to improve the evaluation, monitoring, and management of neonates, infants, or children affected by ZIKV and its complications. The agenda also aims to optimally address the prospective effect of ZIKV exposure on the developing child. The full clinical spectrum of congenital ZIKV syndrome has yet to be elucidated. In addition to the well-described anatomic and neurologic manifestations, clinicians are now describing infants with exaggerated primitive reflexes, epilepsy, acquired hydrocephalus and microcephaly, neurodevelopmental delay, gastrointestinal motility problems, and respiratory complications, such as pneumonia. While we are still learning more about the myriad clinical presentations in these severely affected children, it is also paramount to address the larger proportion of ZIKV-exposed infants who are asymptomatic at birth but, we assume, may develop problems later in life. The available evidence for neurologic, neurodevelopmental, neurobehavioral, auditory, and vision assessments and management for infants with congenital ZIKV syndrome was critically evaluated. Lessons from other congenital infections provide valuable clues about the complexities of management and the optimal approaches for evaluating, treating, and caring for the children, which include engaging and involving parents and caregivers in their treatment. Rigorous research is key to improving the identification of ZIKV-infected mothers and babies. Research also is critical to

Structural Differentiation and Ambidexterity: The Mediating Role of Integration Mechanisms

NARCIS (Netherlands)

J.J.P. Jansen (Justin); M.P. Tempelaar (Michiel); F.A.J. van den Bosch (Frans); H.W. Volberda (Henk)

2008-01-01

textabstractPrior studies have emphasized that structural attributes are crucial to simultaneously pursuing exploration and exploitation, yet our understanding of antecedents of ambidexterity is still limited. Structural differentiation can help ambidextrous organizations to maintain multiple

Structural differentiation and ambidexterity: The mediating role of integration mechanisms

NARCIS (Netherlands)

J.J.P. Jansen (Justin); M.P. Tempelaar (Michiel); F.A.J. van den Bosch (Frans); H.W. Volberda (Henk)

2009-01-01

textabstractPrior studies have emphasized that structural attributes are crucial to simultaneously pursuing exploration and exploitation, yet our understanding of antecedents of ambidexterity is still limited. Structural differentiation can help ambidextrous organizations to maintain multiple

Exposure to Pre- and Perinatal Risk Factors Partially Explains Mean Differences in Self-Regulation between Races.

Science.gov (United States)

Barnes, J C; Boutwell, Brian B; Miller, J Mitchell; DeShay, Rashaan A; Beaver, Kevin M; White, Norman

2016-01-01

To examine whether differential exposure to pre- and perinatal risk factors explained differences in levels of self-regulation between children of different races (White, Black, Hispanic, Asian, and Other). Multiple regression models based on data from the Early Childhood Longitudinal Study, Birth Cohort (n ≈ 9,850) were used to analyze the impact of pre- and perinatal risk factors on the development of self-regulation at age 2 years. Racial differences in levels of self-regulation were observed. Racial differences were also observed for 9 of the 12 pre-/perinatal risk factors. Multiple regression analyses revealed that a portion of the racial differences in self-regulation was explained by differential exposure to several of the pre-/perinatal risk factors. Specifically, maternal age at childbirth, gestational timing, and the family's socioeconomic status were significantly related to the child's level of self-regulation. These factors accounted for a statistically significant portion of the racial differences observed in self-regulation. The findings indicate racial differences in self-regulation may be, at least partially, explained by racial differences in exposure to pre- and perinatal risk factors.