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Sample records for poorly regulated exposure

  1. Health hazard of poorly regulated exposure during manufacture of cemented tungsten carbides and cobalt.

    PubMed

    Auchincloss, J H; Abraham, J L; Gilbert, R; Lax, M; Henneberger, P K; Heitzman, E R; Peppi, D J

    1992-12-01

    Forty two of 125 former workers in a factory in Syracuse, New York, which manufactured hard metal parts from tungsten carbide and cobalt, were studied by chest radiographs, spirometry, and plethysmographically determined lung volumes. The plant was closed in 1982 and the studies were performed in 1983-5. Recorded measurements of carbide dust concentrations were only mildly excessive by modern standards, but deceitful efforts to reduce the apparent concentration of dust were known to have occurred during an inspection by the Occupational Safety and Health Administration. Lung biopsies in four cases in the study and necropsy in one of the 83 cases not studied during life showed giant cell interstitial pneumonia and appreciable concentrations of tungsten carbide. This information indicates that exposure was substantial. Four workers had evidence of pulmonary fibrosis by chest radiographs; two of these workers had normal pulmonary function. Fourteen had abnormal pulmonary function, five of whom had a restrictive pattern, eight a pattern of air trapping, and one a combined pattern. Thus radiographic, or functional abnormalities, or both occurred in 16 of the 42 cases studied. No correlation with duration of exposure was established. Progressive clinically important disease (one fatal) has been found in four ex-workers, two in each of the restrictive and air trapping groups. These findings suggest that poorly regulated dust concentrations in a hard metals factory possibly cause pulmonary abnormalities and sometimes severe illness. PMID:1472440

  2. Household instability and self-regulation among poor children

    PubMed Central

    McCoy, Dana Charles; Raver, C. Cybele

    2015-01-01

    Past research suggests that poverty may negatively influence children’s psychological and behavioral health by increasing their exposure to chaotic living conditions in the household. The present study provides a descriptive ‘snapshot’ of instability in low-income households, and examines the associations between exposure to major destabilizing events over the course of a year and three domains of poor urban children’s self-regulation. Descriptive analyses suggest that although caregivers from unstable households report higher average levels of health problems and depression, they also have greater assets/savings, are more educated, and are less likely to be immigrants than caregivers from stable households. Results of propensity score-matched regression analyses reveal that high levels of household instability are significantly and negatively associated with preschoolers’ effortful control and global attention/impulsivity control, but not with their executive function. Children from mildly unstable homes (i.e., those who had experienced a single destabilizing event in the past year) showed no significant differences in any domain of self-regulation relative to their peers from stable households, suggesting a dose-response relationship between the number of destabilizing events experienced by children and their outcomes. Implications for theories of poverty-related adversity, stress, and parenting are discussed in addition to future directions for research. PMID:26924923

  3. The Effect of Social Programs and Exposure to Professionals on the Educational Aspirations of the Poor

    ERIC Educational Resources Information Center

    Chiapa, Carlos; Garrido, Jose Luis; Prina, Silvia

    2012-01-01

    Investment in human capital is an important tool for reducing poverty. However, the poor may lack the capacity to aspire, which often results in underinvestment in their children's education. This paper studies the effect of a social program on the educational aspirations poor parents have for their children, and explores the role of exposure to…

  4. ESTIMATION OF CHILDREN'S EXPOSURES VIA POORLY CHARACTERIZED PATHWAYS USING CTEPP DATA

    EPA Science Inventory

    This work involved providing better exposure estimates for poorly characterized pathways (dermal and indirect ingestion) for young children in the CTEPP study. The chemicals used in this analysis were chlorpyrifos and its degradation product 3,5,6-trichloro-2-pyridinol.

  5. Genome exposure and regulation in mammalian cells.

    PubMed

    Puck, T T; Webb, P; Johnson, R

    1998-09-01

    fibroblasts as revealed by in situ nick translation reveals a nuclear distribution pattern around the periphery, around the nucleoli and in punctate positions in the nuclear interior in parts of both S and G1 phases of the cell cycle. The same exposure pattern is duplicated by the pattern of DNA synthesis in S cells. It would appear that these nuclear regions represent positions of special activity. The previously proposed theory of genome regulation in mammalian cells is supported by these findings. The theory proposes that: a) gene activity requires exposure of the given locus followed by action of transcription factors on the exposed genes; b) the fiber system of the cell (cytoskeleton, nuclear fibers, and extracellular fibers) are required for normal exposure; c) active sites for gene expression and replication consist of the nuclear periphery where differentiation genes particularly are exposed; the nucleoli where at least some housekeeping genes are exposed; and possibly also punctate regions in the interior; d) noncoding sequences play a critical role in genome regulation, possibly including the transport of loci to be activated to appropriate exposure transcriptional and replicating locations. Cancer cells have lost specific differentiation gene activities, at least sometimes because of mutation of appropriate exposure genes; at least some protooncogenes and tumor suppressor genes are responsible for exposure and transport of specific differentiation gene loci to their appropriate exposure sites in the nucleus and for inducing exposure. PMID:10696237

  6. Infant Self-Regulation and Early Childhood Media Exposure

    PubMed Central

    Silverstein, Michael; Zuckerman, Barry; Christakis, Dimitri A.

    2014-01-01

    OBJECTIVES: Examine prospective associations between parent-reported early childhood self-regulation problems and media exposure (television and video viewing) at 2 years. We hypothesized that children with poor self-regulation would consume more media, possibly as a parent coping strategy. METHODS: We used data from 7450 children in the Early Childhood Longitudinal Study–Birth Cohort. When children were 9 months and 2 years old, parents completed the Infant Toddler Symptom Checklist (ITSC), a validated scale of self-regulation. With daily media use at 2 years as our outcome, we conducted weighted multivariable regression analyses, controlling for child, maternal, and household characteristics. RESULTS: Children watched an average of 2.3 hours per day (SD 1.9) of media at age 2 years. Infants with poor self-regulation (9-month ITSC score ≥3) viewed 0.23 hour per day (95% confidence interval [CI] 0.12–0.35) more media at 2 years compared with those with 9-month ITSC score of 0 to 2; this remained significant in adjusted models (0.15 hour per day [95% CI 0.02–0.28]). Children rated as having persistent self-regulation problems (ITSC ≥3 at both 9 months and 2 years) were even more likely to consume media at age 2 (adjusted β 0.21 hour per day [95% CI 0.03–0.39]; adjusted odds ratio for >2 hours per day 1.40 [95% CI 1.14–1.71]). These associations were slightly stronger in low socioeconomic status and English-speaking households. CONCLUSIONS: Early childhood self-regulation problems are associated with mildly increased media exposure, even after controlling for important confounding variables. Understanding this relationship may provide insight into helping parents reduce their children’s screen time. PMID:24733868

  7. Disaster risk and poverty: assessing the global exposure of the poor to floods and droughts

    NASA Astrophysics Data System (ADS)

    Winsemius, Hessel; Jongman, Brenden; Veldkamp, Ted; Hallegatte, Stéphane; Bangalore, Mook; Ward, Philip

    2015-04-01

    Poor people generally have a lower capacity to deal with the impacts of natural hazards. Yet, in several countries, low-income households have been shown to be disproportionately overrepresented in hazard-prone areas compared to households with higher income. Furthermore, the hazardous conditions under which poor households are exposed to now may become worse due to climate change with resulting increases in intensity and frequency of floods and droughts. To date, the relationship between poverty and natural hazard related disasters has only been explored on a case by case basis in a limited amount of countries. With the recent advances in the global spatial modeling of flood and drought hazard, it becomes feasible to study the relationship between poverty and natural hazards globally. In this presentation we present the most comprehensive analysis so far on the exposure of the global poor to floods and droughts under the current climatic conditions as well as under a range of future climate scenarios. We combine state-of-the-art global river flood and drought hazard models with detailed household asset and income datasets for over 50 countries world-wide, to analyse poverty-specific household exposure to current and future hazard levels.

  8. Violence exposure, sleep disturbance, and poor academic performance in middle school.

    PubMed

    Lepore, Stephen J; Kliewer, Wendy

    2013-11-01

    Violence has been linked to poor academic outcomes in youth, but there is little understanding of the mechanisms underlying this relation. This longitudinal survey study investigated whether sleep disturbance potentially mediates the associations between academic achievement and two forms of violence exposure--community violence and peer victimization-- in 498 seventh-grade youth. Structural equation models showed that community violence was associated with lower grade point average (GPA) directly and indirectly via sleep problems, whereas peer victimization was associated with lower GPA just indirectly via sleep problems. The structural models controlled for potential confounds, including depressive symptoms, intrusive thoughts and absenteeism. The findings suggest that failing grades and sleepiness in school may be signs that youth are exposed to violence. Interventions to improve sleep hygiene and reduce violence exposure may help to improve academic outcomes for youth. PMID:23315234

  9. Violence Exposure, Sleep Disturbance, and Poor Academic Performance in Middle School

    PubMed Central

    Lepore, Stephen J.; Kliewer, Wendy

    2013-01-01

    Violence has been linked to poor academic outcomes in youth, but there is little understanding of the mechanisms underlying this relation. This longitudinal survey study investigated whether sleep disturbance potentially mediates the associations between academic achievement and two forms of violence exposure--community violence and peer victimization-- in 498 seventh-grade youth. Structural equation models showed that community violence was associated with lower grade point average (GPA) directly and indirectly via sleep problems, whereas peer victimization was associated with lower GPA just indirectly via sleep problems. The structural models controlled for potential confounds, including depressive symptoms, intrusive thoughts and absenteeism. The findings suggest that failing grades and sleepiness in school may be signs that youth are exposed to violence. Interventions to improve sleep hygiene and reduce violence exposure may help to improve academic outcomes for youth. PMID:23315234

  10. Children's Negative Emotionality Combined with Poor Self-Regulation Affects Allostatic Load in Adolescence

    ERIC Educational Resources Information Center

    Dich, Nadya; Doan, Stacey; Evans, Gary

    2015-01-01

    The present study examined the concurrent and prospective, longitudinal effects of childhood negative emotionality and self-regulation on allostatic load (AL), a physiological indicator of chronic stress. We hypothesized that negative emotionality in combination with poor self-regulation would predict elevated AL. Mothers reported on children's…

  11. Exposure to violence predicts poor educational outcomes in young children in South Africa and Malawi

    PubMed Central

    Sherr, L.; Hensels, I. S.; Skeen, S.; Tomlinson, M.; Roberts, K. J.; Macedo, A.

    2016-01-01

    Background Violence during childhood may affect short and long-term educational factors. There is scant literature on younger children from resource poor settings. Methods This study assessed child violence experiences (harsh punishment and exposure to domestic or community violence) and school enrolment, progress and attendance in children attending community-based organisations in South Africa and Malawi (n=989) at baseline and at 15 months' follow-up, examining differential experience of HIV positive, HIV affected and HIV unaffected children. Results Violence exposure was high: 45.4% experienced some form of psychological violence, 47.8% physical violence, 46.7% domestic violence and 41.8% community violence. Primary school enrolment was 96%. Violence was not associated with school enrolment at baseline but, controlling for baseline, children exposed to psychological violence for discipline were more than ten times less likely to be enrolled at follow-up (OR 0.09; 95% CI 0.01 to 0.57). Harsh discipline was associated with poor school progress. For children HIV positive a detrimental effect of harsh physical discipline was found on school performance (OR 0.10; 95% CI 0.02 to 0.61). Conclusion Violence experiences were associated with a number of educational outcomes, which may have long-term consequences. Community-based organisations may be well placed to address such violence, with a particular emphasis on the challenges faced by children who are HIV positive. PMID:26678567

  12. Regulation of nuclear radiation exposures in India.

    PubMed

    Mishra, U C

    2004-01-01

    India has a long-term program of wide spread applications of nuclear radiations and radioactive sources for peaceful applications in medicine, industry, agriculture and research and is already having several thousand places in the country where such sources are being routinely used. These places are mostly outside the Department of Atomic Energy (DAE) installations. DAE supplies such sources. The most important application of nuclear energy in DAE is in electricity generation through nuclear power plants. Fourteen such plants are operating and many new plants are at various stages of construction. In view of the above mentioned wide spread applications, Indian parliament through an Act, called Atomic Energy Act, 1964 created an autonomous body called Atomic Energy Regulatory Board (AERB) with comprehensive authority and powers. This Board issues codes, guides, manuals, etc., to regulate such installations so as to ensure safe use of such sources and personnel engaged in such installations and environment receives radiation exposures within the upper bounds prescribed by them. Periodic reports are submitted to AERB to demonstrate compliance of its directives. Health, Safety and Environment Group of Bhabha Atomic Research Centres, Mumbai carries out necessary surveillance and monitoring of all installations of the DAE on a routine basis and also periodic inspections of other installations using radiation sources. Some of the nuclear fuel cycle plants like nuclear power plants and fuel reprocessing involve large radioactive source inventories and have potential of accidental release of radioactivity into the environment, an Environmental Surveillance Laboratory (ESL) is set up at each such site much before the facility goes into operation. These ESL's collect baseline data and monitor the environment throughout the life of the facilities including the decommissioning stage. The data is provided to AERB and is available to members of the public. In addition, a multi

  13. NEK2 regulates stem-like properties and predicts poor prognosis in hepatocellular carcinoma.

    PubMed

    Lin, Shuang; Zhou, Senjun; Jiang, Shaojie; Liu, Xiaolong; Wang, Yifan; Zheng, Xueyong; Zhou, Haimeng; Li, Xuhui; Cai, Xiujun

    2016-08-01

    NEK2 has been estimated to play an important role in cancer progression. However, its relevance in hepatocellular carcinoma (HCC) has not yet been explored. Immunohistochemistry revealed NEK2 expression was upregulated in HCC. NEK2-positive hepatocellular carcinoma patients were associated with poor prognosis after surgery compared with NEK2-negative patients based on Kaplan-Meier curves. Deletion of NEK2 reduced self-renewal properties and chemotherapeutic resistance, and decreased the stemness associated genes in cell lines. NEK2 was associated with unfavorable outcomes in HCC patients, and was revealed to regulate self-renewal property by means of Wnt/β-catenin signaling, and chemotherapeutic resistance by preferential regulation of the expression of ABCG2 and ALDH1A1 in HCC cells. PMID:27349376

  14. Using Behavior Change to Reduce Child Lead Exposure in Resource-Poor Settings: A Formative Study

    ERIC Educational Resources Information Center

    Feit, M. N.; Mathee, A.; Harpham, T.; Barnes, B. R.

    2014-01-01

    The objective of this formative research was to explore the acceptability and feasibility of changing housekeeping behaviors as a low-cost approach that may reduce childhood lead exposure in Johannesburg, South Africa. Using the Trials of Improved Practices (TIPs) methodology, modified housekeeping behaviors were negotiated with participants who…

  15. Do Time in Child Care and Peer Group Exposure Predict Poor Socioemotional Adjustment in Norway?

    ERIC Educational Resources Information Center

    Solheim, Elisabet; Wichstrøm, Lars; Belsky, Jay; Berg-Nielsen, Turid Suzanne

    2013-01-01

    Extensive exposure to nonparental child care during the first 4.5 years of life has been demonstrated in some American studies to negatively affect children's socioemotional functioning. Data from 935 preschool children who averaged 54.9 (SD = 3.0) months of age, from Trondheim, Norway were used to examine whether such negative effects, would…

  16. Prenatal substance exposure and child self-regulation: Pathways to risk and protection.

    PubMed

    Eiden, Rina D; Godleski, Stephanie; Schuetze, Pamela; Colder, Craig R

    2015-09-01

    A conceptual model of the association between prenatal cocaine exposure (PCE) and child self-regulation via maternal harshness and language development was examined. Specifically, the model tested whether PCE was associated with self-regulation either directly or indirectly via high maternal harshness and poor language development. The role of child sex, autonomic reactivity, and cumulative environmental risk as potential moderators was also explored. The sample was 216 mother-child dyads recruited at birth and assessed at 2, 7, 13, 24, 36, and 48 months of child ages. Participating mothers were primarily African American (72%). Results indicated a significant indirect association between PCE and child effortful control at 36 months via higher maternal harshness. Autonomic reactivity moderated the association between maternal harshness and self-regulation such that among children with poor autonomic reactivity, high maternal harshness was associated with lower conscience at 3 years. Child sex and environmental risk did not moderate the association between PCE and self-regulation. Thus, the quality of caregiving experience played a significant role in the development of self-regulation among PCE children, especially those at higher autonomic risk. In particular, PCE children who also exhibit poor autonomic reactivity may be particularly susceptible to environmental influences such as parenting. PMID:25913650

  17. SOX2 Expression Is Regulated by BRAF and Contributes to Poor Patient Prognosis in Colorectal Cancer

    PubMed Central

    Lundberg, Ida V.; Löfgren Burström, Anna; Edin, Sofia; Eklöf, Vincy; Öberg, Åke; Stenling, Roger; Palmqvist, Richard; Wikberg, Maria L.

    2014-01-01

    Sporadic colorectal cancer (CRC) is a common malignancy and also one of the main causes of cancer deaths worldwide. Aberrant expression of the transcription factor SOX2 has recently been observed in several cancer types, but its role in CRC has not been fully elucidated. Here we studied the expression of SOX2 in 441 CRC patients by immunohistochemistry and related the expression to clinicopathological and molecular variables and patient prognosis. SOX2 was expressed in 11% of the tumors and was significantly associated to BRAFV600E mutation, but not to KRAS mutations (codon 12 and 13). SOX2 positivity was correlated to poor patient survival, especially in BRAFV600E mutated cases. In vitro studies showed that cells expressing the constitutively active BRAFV600E had increased SOX2 expression, a finding not found in cells expressing KRASG12V. Furthermore, blocking downstream BRAF signalling using a MEK-inhibitor resulted in a decreased expression of SOX2. Since SOX2 overexpression has been correlated to increased migration and invasion, we investigated the SOX2 expression in human CRC liver metastasis and found that a SOX2 positive primary CRC also had SOX2 expression in corresponding liver metastases. Finally we found that cells overexpressing SOX2 in vitro showed enhanced expression of FGFR1, which has been reported to correlate with liver metastasis in CRC. Our novel findings suggest that SOX2 expression is partly regulated by BRAF signalling, and an increased SOX2 expression may promote CRC metastasis and mediate a poor patient prognosis. PMID:25010701

  18. Dietary salt loading and ion-poor water exposure provide insight into the molecular physiology of the rainbow trout gill epithelium tight junction complex.

    PubMed

    Kolosov, Dennis; Kelly, Scott P

    2016-08-01

    This study utilized dietary salt loading and ion-poor water (IPW) exposure of rainbow trout (Oncorhynchus mykiss) to further understand the role of fish gill epithelium tight junction (TJ) physiology in salt and water balance. Gill morphology, biochemistry and molecular physiology were examined, with an emphasis on genes encoding TJ proteins. Fish were either fed a control or salt-enriched diet (~10 % NaCl) for 4 weeks prior to IPW exposure for 24 h. Serum [Na(+)], [Cl(-)] and muscle moisture content were unaltered by salt feeding, but changed in response to IPW irrespective of diet. Dietary salt loading altered the morphology (reduced Na(+)-K(+)-ATPase-immunoreactive cell numbers and surface exposure of mitochondrion-rich cells), biochemistry (decreased vacuolar-type H(+)-ATPase activity) and molecular physiology (decreased nkaα1a and cftrII mRNA abundance) of the gill in a manner indicative of reduced active ion uptake activity. But in control fish and not salt-fed fish, gill mRNA abundance of nkaα1c increased and nbc decreased after IPW exposure. Genes encoding TJ proteins were typically either responsive to salt feeding or IPW, but select genes responded to combined experimental treatment (e.g. IPW responsive but only if fish were salt-fed). Therefore, using salt feeding and IPW exposure, new insights into what factors influence gill TJ proteins and the role that specific TJ proteins might play in regulating the barrier properties of the gill epithelium have been acquired. In particular, evidence suggests that TJ proteins in the gill epithelium, or the regulatory networks that control them, respond independently to external or internal stimuli. PMID:27083431

  19. Novel Dosing Strategies Increase Exposures of the Potent Antituberculosis Drug Rifapentine but Are Poorly Tolerated in Healthy Volunteers

    PubMed Central

    Savic, Radojka M.; Park, Jeong-Gun; Cramer, Yoninah; Hafner, Richard; Hogg, Evelyn; Janik, Jennifer; Marzinke, Mark A.; Patterson, Kristine; Benson, Constance A.; Hovind, Laura; Dorman, Susan E.; Haas, David W.

    2015-01-01

    Rifapentine is a potent antituberculosis drug currently in phase III trials. Bioavailability decreases with increasing dose, yet high daily exposures are likely needed to improve efficacy and shorten the tuberculosis treatment duration. Further, the limits of tolerability are poorly defined. The phase I multicenter trial in healthy adults described here investigated two strategies to increase rifapentine exposures: dividing the dose or giving the drug with a high-fat meal. In arm 1, rifapentine was administered at 10 mg/kg of body weight twice daily and 20 mg/kg once daily, each for 14 days, separated by a 28-day washout; the dosing sequence was randomized. In arm 2, 15 mg/kg rifapentine once daily was given with a high-fat versus a low-fat breakfast. Sampling for pharmacokinetic analysis was performed on days 1 and 14. Population pharmacokinetic analyses were performed. This trial was stopped early for poor tolerability and because of safety concerns. Of 44 subjects, 20 discontinued prematurely; 11 of these discontinued for protocol-defined toxicity (a grade 3 or higher adverse event or grade 2 or higher rifamycin hypersensitivity). Taking rifapentine with a high-fat meal increased the median steady-state area under the concentration-time curve from time zero to 24 h (AUC0–24ss) by 31% (relative standard error, 6%) compared to that obtained when the drug was taken with a low-fat breakfast. Dividing the dose increased exposures substantially (e.g., 38% with 1,500 mg/day). AUC0–24ss was uniformly higher in our study than in recent tuberculosis treatment trials, in which toxicity was rare. In conclusion, two strategies to increase rifapentine exposures, dividing the dose or giving it with a high-fat breakfast, successfully increased exposures, but toxicity was common in healthy adults. The limits of tolerability in patients with tuberculosis remain to be defined. (AIDS Clinical Trials Group study A5311 has been registered at ClinicalTrials.gov under registration

  20. Occupational exposures to uranium: processes, hazards, and regulations

    SciTech Connect

    Stoetzel, G.A.; Fisher, D.R.; McCormack, W.D.; Hoenes, G.R.; Marks, S.; Moore, R.H.; Quilici, D.G.; Breitenstein, B.D.

    1981-04-01

    The United States Uranium Registry (USUR) was formed in 1978 to investigate potential hazards from occupational exposure to uranium and to assess the need for special health-related studies of uranium workers. This report provides a summary of Registry work done to date. The history of the uranium industry is outlined first, and the current commercial uranium industry (mining, milling, conversion, enrichment, and fuel fabrication) is described. This description includes information on basic processes and areas of greatest potential radiological exposure. In addition, inactive commercial facilities and other uranium operations are discussed. Regulation of the commercial production industry for uranium fuel is reported, including the historic development of regulations and the current regulatory agencies and procedures for each phase of the industry. A review of radiological health practices in the industry - facility monitoring, exposure control, exposure evaluation, and record-keeping - is presented. A discussion of the nonradiological hazards of the industry is provided, and the final section describes the tissue program developed as part of the Registry.

  1. Association of pancreatic adenocarcinoma up-regulated factor expression in ovarian mucinous adenocarcinoma with poor prognosis.

    PubMed

    Kim, Sang Kyum; Song, Si Young; Kim, Sunghoon; Cho, Nam Hoon; Yim, Ga Won; Kim, Sang Wun; Kim, Young Tae; Nam, Eun Ji

    2014-01-01

    Pancreatic adenocarcinoma up-regulated factor (PAUF) expression is elevated in both ovarian tumors and pancreatic adenocarcinoma. However, PAUF expression in ovarian tumors according to histologic subtype and grade has not been investigated. In this study, we examined various clinicopathologic features of 24 patients with mucinous cystadenoma (MCA), 36 with mucinous borderline tumors (MBTs), and 46 with mucinous adenocarcinomas (MACs) according to PAUF expression status assessed using immunohistochemistry. We found that MACs more frequently stained positive for PAUF than did MCAs and MBTs (P < 0.0001). Although there was no significant differences with respect to other clinicopathologic characteristics of MACs according to PAUF expression status, patients with PAUF-weakly positive and PAUF-strongly positive MACs tended to have a shorter overall survival (OS) than those with PAUF-negative MAC, determined using a Kaplan-Meier analysis (P = 0.1885). After adjusting for various clinicopathologic parameters, PAUF positivity of MACs was a significant predictive factor for disease-free survival (DFS) (negative vs. weakly positive: P = 0.045, hazard ratio [HR] = 57.406, 95% confidence interval [CI]: 1.090-3022.596; and negative vs. strongly positive: P = 0.034, HR = 97.890, 95% CI: 1.412-6785.925). In conclusion, PAUF was more frequently expressed in MAC than in its benign and borderline counterparts, and was associated with a poor OS and DFS in MAC patients. Therefore, we suggest that PAUF may be a practical biomarker for histopathological categorization and a prognostic marker for patients with an ovarian mucinous tumor. PMID:25197383

  2. Up-regulation of Tim-3 is associated with poor prognosis of patients with colon cancer

    PubMed Central

    Zhou, Encheng; Huang, Qing; Wang, Ji; Fang, Chengfeng; Yang, Leilei; Zhu, Min; Chen, Jianhui; Chen, Lihua; Dong, Milian

    2015-01-01

    Tim-3 (T cell immunoglobulin and mucin domain 3), belonging to the member of the novel Tim family, has been confirmed that it plays a critical negative role in regulating the immune responses against viral infection and carcinoma. Recently, it has also been reported that the over-expression of Tim-3 is associated with poor prognosis in solid tumors. However, the role of Tim-3 in colorectal cancer remains largely unknown. In the current study, we aim to investigate the expression of Tim-3 in colorectal carcinoma and discuss the relationship between Tim-3 expression and colon cancer prognosis, thus speculating the possible role of Tim-3 in colon cancer progression. Colon cancer tissues and paired normal tissue were obtained from 201 patients with colon cancer for preparation of tissue microarray. Tim-3 expression was evaluated by immunohistochemical staining. The Tim-3 expression level was evaluated by q-RT-PCR, western blot and immunocytochemistry in four colon cancer cell lines (HT-29, HCT116, LoVo, SW620). Tim-3 was expressed in 92.5% tumor tissue samples and 86.5% corresponding normal tissue samples. Expression of Tim-3 was significantly higher in tumor tissues than in normal tissues (P < 0.0001). Tim-3 expression in colon cancer tissues is in correlation with colon cancer lymphatic metastasis and TNM (P < 0.0001). Multivariate analysis demonstrated that Tim-3 expression could be a potential independent prognostic factor for colon cancer patients (P < 0.0001). Kaplan-Meier survival analysis result showed that patients with higher Tim-3 expression had a significantly shorter survival time than those with lower Tim-3 expression patients. Our results indicated that Tim-3 might participate in the tumorgenesis of colon cancer and Tim-3 expression might be a potential independent prognostic factor for patients with colorectal cancer. PMID:26339368

  3. Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage

    PubMed Central

    Luo, Hanwen; Li, Jing; Cao, Hong; Tan, Yang; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway. PMID:26639318

  4. Down-regulation of sirtuin 3 is associated with poor prognosis in hepatocellular carcinoma after resection

    PubMed Central

    2014-01-01

    Background Sirtuin 3 (Sirt3), one of the seven Sirtuins family members, plays critical roles in the progression of multiple cancer types. However, its role in the prognosis of hepatocellular carcinoma (HCC) has not yet been investigated systematically. Methods The correlation of Sirtuins expression with prognosis of HCC was determined by immunohistochemistry (IHC) in a large HCC patient cohort (n = 342). Expression of Sirt3 in tumoral and peritumoral tissues of HCC patients were further determined by western blotting (WB). Results IHC and WB studies both showed a decreased expression of Sirt3 in tumoral tissues compared with peritumoral tissues (P = 0.003 for IHC, P = 0.0042 for WB). Decreased expression of Sirt3 in both tumoral and peritumoral tissues was associated with increased recurrence probability and decreased overall survival rate by univariate analyses (intratumoral Sirt3: P = 0.011 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.017 for TTR, P = 0.023 for OS), the prognostic value was strengthened by multivariate analyses (intratumoral Sirt3: P = 0.031 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.047 for TTR, P = 0.031 for OS). Intratumoral Sirt3 also showed a favorable prognostic value in patients with BCLC stage A (TTR, P = 0.011; OS, P < 0.001). In addition, we found that IHC studies of other sirtuin members showed a decreased expression of Sirt2, Sirt4 and Sirt5 and an increased expression of Sirt1, Sirt6 and Sirt7 in intratumoral tissues compared with peritumoral tissues. In contrast to Sirt3, other members did not showed a remarkable correlation with HCC prognosis. Conclusions Down-regulation of intratumoral and peritumoral Sirt3 were both associated with poor outcome in HCC, moreover, intratumoral Sirt3 was a favorable prognostic predictor in early stage patients. PMID:24774224

  5. Gender differences in blood pressure regulation following artificial gravity exposure

    NASA Astrophysics Data System (ADS)

    Evans, Joyce; Goswami, Nandu; Kostas, Vladimir; Zhang, Qingguang; Ferguson, Connor; Moore, Fritz; Stenger, Michael, , Dr; Serrador, Jorge; W, Siqi

    study, men and women demonstrated significantly different strategies for regulating blood pressure and cerebral flow both at rest and during orthostatic stress on the day in which they had undergone exposure to AG. Since, in both men and women, a single, acute bout of AG exposure improved orthostatic tolerance, the feasibility of short exposures to AG during longer spaceflights or prior to entry into a gravitational (Earth or Mars) environment, should be explored. Given the known beneficial effects of AG on other organ systems, the present study indicates that the positive effect of artificial gravity on cardiac output make AG a likely candidate for sustaining cardiovascular conditioning upon return to gravity. Supported by KY NASA EPSCoR Grant #NNX07AT58A, KY State Matching Grants, NASA JSC Human Research Program and NASA Ames Research Center.

  6. Cocaine Exposure and Children's Self-Regulation: Indirect Association via Maternal Harshness

    PubMed Central

    Eiden, Rina D.; Schuetze, Pamela; Veira, Yvette; Cox, Elizabeth; Jarrett, Thomas M.; Johns, Josephine M.

    2011-01-01

    Objectives: This study examined the association between prenatal cocaine exposure and children’s self-regulation at 3 years of child age. In addition to direct effects of prenatal cocaine exposure on children’s self-regulation, we hypothesized there would be indirect associations between cocaine exposure and self-regulation via higher maternal harshness and poor autonomic regulation in infancy. Methods: The sample consisted of 216 mother–infant dyads recruited at delivery from local area hospitals (116 cocaine-exposed, 100 non-exposed). Infant autonomic regulation was measured at 7 months of age during an anger/frustration task, maternal harshness was coded from observations of mother–toddler interactions at 2 years of age, and children’s self-regulation was measured at 3 years of age using several laboratory paradigms. Results: Contrary to hypotheses, there were no direct associations between maternal cocaine use during pregnancy and children’s self-regulation. However, results from testing our conceptual model including the indirect effects via maternal harshness or infant parasympathetic regulation indicated that this model fit the data well, χ2 (23) = 34.36, p > 0.05, Comparative Fit Index = 0.95, RMSEA = 0.05. Cocaine using mothers displayed higher intensity of harshness toward their toddlers during lab interactions across a variety of tasks at 2 years of age (β = 0.23, p < 0.05), and higher intensity of harshness at 2 years was predictive of lower self-regulation at 3 years (β = −0.36, p < 0.01). Maternal cocaine use was also predictive of a non-adaptive increase in respiratory sinus arrhythmia (RSA) from baseline to the negative affect task, but RSA change in infancy was not predictive of self-regulation at 3 years. Conclusion: Results are supportive of animal models indicating higher aggression among cocaine treated dams, and indicate that higher maternal harshness among cocaine using mothers

  7. Theoretical estimates of exposure timescales of protein binding sites on DNA regulated by nucleosome kinetics.

    PubMed

    Parmar, Jyotsana J; Das, Dibyendu; Padinhateeri, Ranjith

    2016-02-29

    It is being increasingly realized that nucleosome organization on DNA crucially regulates DNA-protein interactions and the resulting gene expression. While the spatial character of the nucleosome positioning on DNA has been experimentally and theoretically studied extensively, the temporal character is poorly understood. Accounting for ATPase activity and DNA-sequence effects on nucleosome kinetics, we develop a theoretical method to estimate the time of continuous exposure of binding sites of non-histone proteins (e.g. transcription factors and TATA binding proteins) along any genome. Applying the method to Saccharomyces cerevisiae, we show that the exposure timescales are determined by cooperative dynamics of multiple nucleosomes, and their behavior is often different from expectations based on static nucleosome occupancy. Examining exposure times in the promoters of GAL1 and PHO5, we show that our theoretical predictions are consistent with known experiments. We apply our method genome-wide and discover huge gene-to-gene variability of mean exposure times of TATA boxes and patches adjacent to TSS (+1 nucleosome region); the resulting timescale distributions have non-exponential tails. PMID:26553807

  8. Poor Indoor Air Quality, Mold Exposure, and Upper Respiratory Tract Infections--Are We Placing Our Children at Risk?

    PubMed

    Polyzois, Dimos; Polyzoi, Eleoussa; Wells, John A; Koulis, Theo

    2016-03-01

    Understanding how respiratory health risks are associated with poor housing is essential to designing effective strategies to improve children's quality of life. The objective of the study described in this article was to determine the relationship between respiratory health and housing conditions. A survey was completed by 3,424 parents of children in third and fourth grade in Winnipeg, Manitoba, Canada. An engineering audit and air samples were also taken in the homes of a subset of 715 homes. Results showed that a child's respiratory health is significantly associated with self-reported visible mold in the home and that a significant association existed between occupant-reported visible mold and tested airborne mold. Findings highlight the need for clearer standards of acceptable CFU/m3 limits for mold genera that are applicable to homes. In the absence of such guidelines, problems associated with indoor mold will continue to impact the health of residents, despite growing evidence of the adverse effects from mold exposure. PMID:27197351

  9. Mercy Mercy Me: Social Injustice and the Prevention of Environmental Pollutant Exposures among Ethnic Minority and Poor Children

    ERIC Educational Resources Information Center

    Dilworth-Bart, Janean E.; Moore, Colleen F.

    2006-01-01

    Children's lead and pesticide exposures are used as examples to examine social disparities in exposure reduction efforts as well as environmental policies impacting children in poverty and minority children. The review also presents an estimate of the effect of social disparities in lead exposure on standardized test performance. Because including…

  10. Differential regulation of HIF-1α and HIF-2α in neuroblastoma: Estrogen-related receptor alpha (ERRα) regulates HIF2A transcription and correlates to poor outcome

    SciTech Connect

    Hamidian, Arash; Stedingk, Kristoffer von; Munksgaard Thorén, Matilda; Mohlin, Sofie; Påhlman, Sven

    2015-06-05

    Hypoxia-inducible factors (HIFs) are differentially regulated in tumor cells. While the current paradigm supports post-translational regulation of the HIF-α subunits, we recently showed that hypoxic HIF-2α is also transcriptionally regulated via insulin-like growth factor (IGF)-II in the childhood tumor neuroblastoma. Here, we demonstrate that transcriptional regulation of HIF-2α seems to be restricted to neural cell-derived tumors, while HIF-1α is canonically regulated at the post-translational level uniformly across different tumor forms. Enhanced expression of HIF2A mRNA at hypoxia is due to de novo transcription rather than increased mRNA stability, and chemical stabilization of the HIF-α proteins at oxygen-rich conditions unexpectedly leads to increased HIF2A transcription. The enhanced HIF2A levels do not seem to be dependent on active HIF-1. Using a transcriptome array approach, we identified members of the Peroxisome proliferator-activated receptor gamma coactivator (PGC)/Estrogen-related receptor (ERR) complex families as potential regulators of HIF2A. Knockdown or inhibition of one of the members, ERRα, leads to decreased expression of HIF2A, and high expression of the ERRα gene ESRRA correlates with poor overall and progression-free survival in a clinical neuroblastoma material consisting of 88 tumors. Thus, targeting of ERRα and pathways regulating transcriptional HIF-2α are promising therapeutic avenues in neuroblastoma. - Highlights: • Transcriptional control of HIF-2α is restricted to neural cell-derived tumors. • Enhanced transcription of HIF2A is not due to increased mRNA stability. • Chemical stabilization of the HIF-α subunits leads to increased HIF2A transcription. • ERRα regulates HIF2A mRNA expression in neuroblastoma. • High expression of ESRRA correlates to poor outcome in neuroblastoma.

  11. Down-regulation of Barx2 predicts poor survival in colorectal cancer.

    PubMed

    Mi, Yushuai; Zhao, Senlin; Zhang, Weihao; Zhang, Dongyuan; Weng, Junyong; Huang, Kejian; Sun, Huimin; Tang, Huamei; Zhang, Xin; Sun, Xiaofeng; Peng, Zhihai; Wen, Yugang

    2016-09-01

    Human BarH-like homeobox 2 (Barx2), a homeodomain factor of the Bar family, has an important role in controlling the expression of cell adhesion molecules and has been reported in an increasing array of tumor types except colorectal cancer (CRC). The purpose of the current study was to characterize the expression of Barx2 and assess the clinical significance of Barx2 in CRC. First, we analyzed the expression of Barx2 in two independent public datasets from Oncomine. Subsequently, we evaluated Barx2 mRNA and protein expression by quantitative real-time PCR and western blotting, respectively. It was determined that Barx2 expression was lower in tumor tissues than in adjacent non-tumorous colorectal tissues of CRC patients, consistent with results from the public datasets. Subsequently, a tissue microarray containing 196 CRC specimens was evaluated for Barx2 expression by immunohistochemical staining. It was found that low expression of Barx2 significantly correlated with TNM stage, AJCC stage, differentiation, and relapse in patients with CRC. Patients with lower levels of Barx2 expression showed reduced disease-free survival and overall survival. Furthermore, a trend toward shorter overall survival in the patient group with Barx2-negative tumors independent of advanced AJCC stage and poor differentiation was determined by Kaplan-Meier survival analysis. Based on univariate and multivariate analyses, Barx2 expression was an independent prognostic factor for determining CRC prognosis. Taken together, low Barx2 expression was associated with the progression of CRC and could serve as a potential independent prognostic biomarker for patients with CRC. PMID:27453340

  12. Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

    SciTech Connect

    Herbert, Katharine J.; Holloway, Adele; Cook, Anthony L.; Chin, Suyin P.; Snow, Elizabeth T.

    2014-11-15

    Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

  13. Stathmin1 regulates p27 expression, proliferation and drug resistance, resulting in poor clinical prognosis in cholangiocarcinoma

    PubMed Central

    Watanabe, Akira; Suzuki, Hideki; Yokobori, Takehiko; Tsukagoshi, Mariko; Altan, Bolag; Kubo, Norio; Suzuki, Shigemasa; Araki, Kenichiro; Wada, Satoshi; Kashiwabara, Kenji; Hosouchi, Yasuo; Kuwano, Hiroyuki

    2014-01-01

    Patients with extrahepatic cholangiocarcinoma (EHCC) have a poor prognosis; postoperative survival depends on cancer progression and therapeutic resistance. The mechanism of EHCC progression needs to be clarified to identify ways to improve disease prognosis. Stathmin1 (STMN1) is a major cytosolic phosphoprotein that regulates microtubule dynamics and is associated with malignant phenotypes and chemoresistance in various cancers. Recently, STMN1 was reported to interact with p27, an inhibitor of cyclin-dependent kinase complexes. Eighty EHCC cases were studied using immunohistochemistry and clinical pathology to determine the correlation between STMN1 and p27 expression; RNA interference to analyze the function of STMN1 in an EHCC cell line was also used. Cytoplasmic STMN1 expression correlated with venous invasion (P = 0.0021) and nuclear p27 underexpression (P = 0.0011). Patients in the high-STMN1-expression group were associated with shorter recurrence-free survival and overall survival than those in the low-expression group. An in vitro protein-binding assay revealed that cytoplasmic STMN1 bound to p27 in the cytoplasm, but not in the nucleus of EHCC cells. Moreover, p27 accumulated in EHCC cells after STMN1 suppression. STMN1 knockdown inhibited proliferation and increased the sensitivity of EHCC cells to paclitaxel. STMN1 contributes to a poor prognosis and cancer progression in EHCC patients. Understanding the regulation of p27 by STMN1 could provide new insights for overcoming therapeutic resistance in EHCC. PMID:24708177

  14. PFKL/miR-128 axis regulates glycolysis by inhibiting AKT phosphorylation and predicts poor survival in lung cancer.

    PubMed

    Yang, Jie; Li, Jingqiu; Le, Yanping; Zhou, Chengwei; Zhang, Shun; Gong, Zhaohui

    2016-01-01

    MicroRNAs (miRNAs) affect cancer cell glucose metabolism by targeting mRNAs of diverse enzymes that have been implicated in oxidative phosphorylation (OXPHOS) and glycolytic pathways. However, the mechanisms that underlie miRNA-mediated regulation of phosphofructokinase (PFK), a key rate-limiting enzyme in glycolysis, remain largely unknown. Here, we show that miR-128 directly targets PFK liver type (PFKL) in lung cancer cells and regulates endogenous expression of PFKL at both the mRNA and protein levels. In line with this, overexpression of miR-128 decreased glucose uptake and lactate production, as well as increased cellular ATP content. Interestingly, knockdown of miR-128 was shown to promote lung cancer cell growth and colony formation. Moreover, we observed that miR-128 expression inversely correlated with PFKL mRNA levels in clinic lung cancer samples and that increased PFKL expression predicted poor overall survival in lung cancer patients. Mechanistically, we showed that miR-128 regulates PFKL via a feedback loop that involves inhibition of the AKT signaling pathway. Together, our results suggest that miR-128 acts as a metabolic regulator in lung cancer cells that may be therapeutically exploited. PMID:27186417

  15. PFKL/miR-128 axis regulates glycolysis by inhibiting AKT phosphorylation and predicts poor survival in lung cancer

    PubMed Central

    Yang, Jie; Li, Jingqiu; Le, Yanping; Zhou, Chengwei; Zhang, Shun; Gong, Zhaohui

    2016-01-01

    MicroRNAs (miRNAs) affect cancer cell glucose metabolism by targeting mRNAs of diverse enzymes that have been implicated in oxidative phosphorylation (OXPHOS) and glycolytic pathways. However, the mechanisms that underlie miRNA-mediated regulation of phosphofructokinase (PFK), a key rate-limiting enzyme in glycolysis, remain largely unknown. Here, we show that miR-128 directly targets PFK liver type (PFKL) in lung cancer cells and regulates endogenous expression of PFKL at both the mRNA and protein levels. In line with this, overexpression of miR-128 decreased glucose uptake and lactate production, as well as increased cellular ATP content. Interestingly, knockdown of miR-128 was shown to promote lung cancer cell growth and colony formation. Moreover, we observed that miR-128 expression inversely correlated with PFKL mRNA levels in clinic lung cancer samples and that increased PFKL expression predicted poor overall survival in lung cancer patients. Mechanistically, we showed that miR-128 regulates PFKL via a feedback loop that involves inhibition of the AKT signaling pathway. Together, our results suggest that miR-128 acts as a metabolic regulator in lung cancer cells that may be therapeutically exploited. PMID:27186417

  16. Up-Regulation of Long Non-Coding RNA AB073614 Predicts a Poor Prognosis in Patients with Glioma.

    PubMed

    Hu, Lei; Lv, Qiao-Li; Chen, Shu-Hui; Sun, Bao; Qu, Qiang; Cheng, Lin; Guo, Ying; Zhou, Hong-Hao; Fan, Lan

    2016-01-01

    Dysregulated long noncoding RNAs (lncRNAs) have been found in human diseases, especially in cancer. Emerging evidence indicates that dysregulated lncRNAs are implicated in tumorigenesis and cancer progression. LncRNA AB073614 characterized as a new candidate lncRNA promotes the development of ovarian cancer. However, the role of lncRNA AB073614 in human gliomas remains unknown. The expression of AB073614 was detected in 65 glioma tissues and 13 normal brain tissues by qRT-PCR, showing that lncRNA AB073614 expression was significantly up-regulated in cancerous tissues compared with normal brain tissues (p < 0.001), and it was positively correlated with tumor grade (I-II grades vs. III-IV grades, p = 0.013) in glioma patients. Kaplan-Meier analysis demonstrated that increased AB073614 expression contributed to poor overall survival (HR (hazard ratio) = 1.952, 95%CI: 1.202-3.940, p = 0.0129). Further, univariate Cox regression analysis indicated that lncRNA AB073614 overexpression was an unfavorable prognostic factor in gliomas (HR = 1.997, 95%CI: 1.135-3.514, p = 0.016), regardless of the tumor grade (I-II grades vs. III-IV grades, HR = 1.902, 95%CI: 1.066-3.391, p = 0.029). Finally, after adjustment with age, sex, tumor grade and tumor location, multivariate Cox regression analysis suggested that both highly expressed lncRNA AB073614 (HR = 2.606, 95%CI: 1.408-4.824, p = 0.002) and high tumor grade (III-IV grades, HR = 2.720, 95%CI: 1.401-5.282, p = 0.003) could be considered independent poor prognostic indicators for glioma patients. In conclusion, our study suggested that increased lncRNA AB073614 expression may be identified as a poor prognostic biomarker in gliomas. PMID:27104549

  17. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    SciTech Connect

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei; Lu, Su; Tang, Huamei; Peng, Zhihai

    2014-06-27

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation.

  18. PDK-1 regulates lactate production in hypoxia and is associated with poor prognosis in head and neck squamous cancer

    PubMed Central

    Wigfield, S M; Winter, S C; Giatromanolaki, A; Taylor, J; Koukourakis, M L; Harris, A L

    2008-01-01

    Here we describe the expression and function of a HIF-1-regulated protein pyruvate dehydrogenase kinase-1 (PDK-1) in head and neck squamous cancer (HNSCC). Using RNAi to downregulate hypoxia-inducible PDK-1, we found that lactate and pyruvate excretion after 16–48 h of hypoxia was suppressed to normoxic levels. This indicates that PDK-1 plays an important role in maintaining glycolysis. Knockdown had no effect on proliferation or survival under hypoxia. The immunohistochemical expression of PDK-1 was assessed in 140 cases of HNSCC. PDK-1 expression was not expressed in normal tissues but was upregulated in HNSCC and found to be predominantly cytoplasmic with occasional strong focal nuclear expression. It was strongly related to poor outcome (P=0.005 split by median). These results indicate that HIF regulation of PDK-1 has a key role in maintaining lactate production in human cancer and that the investigation of PDK-1 inhibitors should be investigated for antitumour effects. PMID:18542064

  19. Smoking and Secondhand Smoke Exposure at Home Were Associated with Poor Perceived Family Well-Being: Findings of FAMILY Project

    PubMed Central

    Wang, Xin; Wang, Man Ping; Viswanath, Kasisomayajula; Wan, Alice; Lam, Tai Hing; Chan, Sophia S.

    2016-01-01

    Introduction To investigate the associations of cigarette smoking and secondhand (SHS) exposure at home with family well-being among Chinese adults in Hong Kong. Methods Telephone surveys were conducted among 3043 randomly selected adults (response rate 70%) in 2010 and 2012 to monitor family health information and tobacco use in Hong Kong. Family well-being was measured using three questions of perceived family harmony, happiness and health (3Hs) with responses ranging from 0–10 and a higher score indicating better family well-being. Smoking status, nicotine dependence, quitting behaviours and SHS exposure at home were recorded. Multiple linear regressions were used to calculate β-coefficients for individual family 3Hs component and an overall composite score representing family well-being. Results Compared with never smokers, current smokers reported lower levels of family harmony (adjusted β = -0.15, 95% CI: -0.35 to -0.10), happiness (adjusted β = -0.12, 95% CI: -0.28 to -0.02), health (adjusted β = -0.15, 95% CI: -0.30 to -0.03) and overall family well-being (adjusted β = -0.17, 95% CI: -0.32 to -0.06). Quit attempt and intention to quit were not associated with family well-being. SHS exposure at home was associated with lower levels of family harmony (adjusted β = -0.17, 95% CI: -0.30 to -0.07), happiness (adjusted β = -0.19, 95% CI: -0.32 to -0.08), health (adjusted β = -0.13, 95% CI: -0.26 to -0.03) and family well-being (adjusted β = -0.19, 95% CI: -0.32 to -0.09). Conclusions Smoking and SHS exposure at home were associated with the lower levels of perceived family well-being. Prospective studies are needed to confirm the results. PMID:27560663

  20. Increased Expression of SETD7 Promotes Cell Proliferation by Regulating Cell Cycle and Indicates Poor Prognosis in Hepatocellular Carcinoma

    PubMed Central

    Hu, Jiewei; Yu, Chaoqin; He, Miaoxia; Cai, Zailong

    2016-01-01

    Purpose To investigate the role of SET domain containing 7 (SETD7) in hepatocellular carcinoma (HCC) and determine whether SETD7 can be used as a predictor of overall survival in HCC patients. Methods mRNAs and proteins of SETD7 and related genes in HCC tumor samples and paired adjacent non-tumorous liver tissues (ANLTs) (n = 20) or culture cells were determined by quantitative real-time PCR and Western blot. Cell proliferation and apoptosis with SETD7 knockdown SMMC-7721 cells or SETD7 overexpressed HepG2 cells were analyzed by CCK8 assay or flow cytometry. Gene expression alterations in SETD7 knockdown of SMMC-7721 cells were determined by digital gene expression (DGE) profiling. Defined data on patients (n = 225) with HCC were retrieved for the further study. Tissue microarrays (TMAs) were performed using paraffin tissues with tumor and ANLTs. SETD7 and related proteins were determined by TMAs immunohistochemistry. Statistical analyses were conducted to associate SETD7 expression with tumor features and patient outcomes, as well as related proteins expression. Results SETD7 expression was significantly higher in HCC tumor tissues than in ANLTs. SETD7 overexpression in vitro can promote HepG2 cell proliferation, whereas SETD7 knockdown can inhibit SMMC-7721 cell proliferation by regulating the cell cycle. SETD7 expression was significantly correlated with five genes expression. Increased SETD7 is associated with metastasis, recurrence, large tumor size, and poor tumor differentiation, and indicates poor prognosis in HCC patients. Conclusions SETD7 plays a critical role in HCC, and its immunohistochemistry signature provides potential clinical significance for personalized prediction of HCC prognosis. PMID:27183310

  1. Up-Regulation of Long Non-Coding RNA AB073614 Predicts a Poor Prognosis in Patients with Glioma

    PubMed Central

    Hu, Lei; Lv, Qiao-Li; Chen, Shu-Hui; Sun, Bao; Qu, Qiang; Cheng, Lin; Guo, Ying; Zhou, Hong-Hao; Fan, Lan

    2016-01-01

    Dysregulated long noncoding RNAs (lncRNAs) have been found in human diseases, especially in cancer. Emerging evidence indicates that dysregulated lncRNAs are implicated in tumorigenesis and cancer progression. LncRNA AB073614 characterized as a new candidate lncRNA promotes the development of ovarian cancer. However, the role of lncRNA AB073614 in human gliomas remains unknown. The expression of AB073614 was detected in 65 glioma tissues and 13 normal brain tissues by qRT-PCR, showing that lncRNA AB073614 expression was significantly up-regulated in cancerous tissues compared with normal brain tissues (p < 0.001), and it was positively correlated with tumor grade (I–II grades vs. III–IV grades, p = 0.013) in glioma patients. Kaplan-Meier analysis demonstrated that increased AB073614 expression contributed to poor overall survival (HR (hazard ratio) = 1.952, 95%CI: 1.202–3.940, p = 0.0129). Further, univariate Cox regression analysis indicated that lncRNA AB073614 overexpression was an unfavorable prognostic factor in gliomas (HR = 1.997, 95%CI: 1.135–3.514, p = 0.016), regardless of the tumor grade (I–II grades vs. III–IV grades, HR = 1.902, 95%CI: 1.066–3.391, p = 0.029). Finally, after adjustment with age, sex, tumor grade and tumor location, multivariate Cox regression analysis suggested that both highly expressed lncRNA AB073614 (HR = 2.606, 95%CI: 1.408–4.824, p = 0.002) and high tumor grade (III–IV grades, HR = 2.720, 95%CI: 1.401–5.282, p = 0.003) could be considered independent poor prognostic indicators for glioma patients. In conclusion, our study suggested that increased lncRNA AB073614 expression may be identified as a poor prognostic biomarker in gliomas. PMID:27104549

  2. Effectiveness of clopidogrel dose escalation to normalize active metabolite exposure and antiplatelet effects in CYP2C19 poor metabolizers.

    PubMed

    Horenstein, Richard B; Madabushi, Rajnikanth; Zineh, Issam; Yerges-Armstrong, Laura M; Peer, Cody J; Schuck, Robert N; Figg, William Douglas; Shuldiner, Alan R; Pacanowski, Michael A

    2014-08-01

    Carriers of two copies of the loss-of-function CYP2C19*2 variant convert less clopidogrel into its active metabolite, resulting in diminished antiplatelet responses and higher cardiovascular event rates. To evaluate whether increasing the daily clopidogrel dose in poor metabolizers (PM) overcomes the effect of the CYP2C19 * 2 variant, we enrolled 18 healthy participants in a genotype-stratified, multi-dose, three-period, fixed-sequence crossover study. Six participants with the *1/*1 extensive (EM), *1/*2 intermediate (IM), and *2/*2 poor metabolizer genotypes each received 75 mg, 150 mg, and 300 mg each for 8 days. In each period, maximal platelet aggregation 4 hours post-dose (MPA4) and active metabolite area under the curve (AUC) differed among genotype groups (P < .05 for all). At day 8, PMs needed 300 mg daily and IMs needed 150 mg daily to attain a similar MPA4 as EMs on the 75 mg dose (32.6%, 33.2%, 31.3%, respectively). Similarly, PMs needed 300 mg daily to achieve active metabolite concentrations that were similar to EMs on 75 mg (AUC 37.7 and 33.5 ng h/mL, respectively). These results suggest that quadrupling the usual clopidogrel dose might be necessary to overcome the effect of poor CYP2C19 metabolism. PMID:24710841

  3. High expression of myofibrillogenesis regulator-1 predicts poor prognosis for patients with hepatocellular carcinoma after curative hepatectomy

    PubMed Central

    Wang, Chunwei; Xiang, Hua; Si, Huiyuan; Guo, Dandan; Sun, Mei

    2015-01-01

    Myofibrillogenesis regulator (MR-1) is overexpressed in human cancer cells and plays an essential role in cancer cell growth. However, its role in hepatocellular carcinoma (HCC) has not yet been explored. The aim of this study was to investigate the association of MR-1 expression with clinicopathologic features and prognosis in patients with HCC. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to detect MR-1 mRNA levels in tissues samples from 120 HCC patients. Results showed that MR-1 expression was significantly higher in HCC tissues when compared with matched adjacent normal tissues (P=0.004). In HCC cancerous tissues, it was also significantly associated with tumor size (P=0.024) and serum AFP level (P=0.003). Moreover, Kaplan-Meier analysis showed that HCC patients with high MR-1 expression had shorter overall survival time than those with low MR-1 expression (P=0.009). When analyzed with a multivariate Cox regression model, MR-1 was identified as an independent prognostic factor for overall survival. Furthermore, when combined with serum AFP level, the median survival time significantly differed between patients with baseline high serum AFP and high MR-1 expression levels and those with normal AFP and low MR-1 levels (P=0.007). Taken together, our results suggest that high expression of MR-1 is involved in HCC progression and could be a novel biomarker of poor prognosis in patients with HCC. PMID:26823810

  4. Proactive Regulation Reduces Asbestos Exposures in Lake County, CA

    NASA Astrophysics Data System (ADS)

    Gearhart, D.; Ley, J. F.

    2012-12-01

    The Lake County Air Quality Management District adopted its rule for Naturally Occurring Asbestos (NOA) in 1996 with the goal of preventing impacts and exposures through education, proactive project design, and common sense. Utilizing detailed GIS mapping and streamlined mitigation measures, the District maintains an effective program to reduce the hazard of NOA in our community. Measures for NOA are also incorporated into the County Grading Ordinance, and most small projects fall under those rules. Larger projects require a Serpentine Dust Control Plan from the District that provides clear mitigation measures, with the focus primarily on dust prevention. This cooperative approach results in a comprehensive effort to minimize potential health hazards from naturally occurring asbestos. Compliance is more easily achieved when workers are informed of the hazards and potential for exposure, and the rules/mitigation measures are clear and simple. Informed individuals generally take prompt corrective action to protect themself and those around them from the potential for breathing asbestos-containing dust. This proactive program results in improved community health by preventing exposure to asbestos.

  5. Childhood trauma exposure disrupts the automatic regulation of emotional processing.

    PubMed

    Marusak, Hilary A; Martin, Kayla R; Etkin, Amit; Thomason, Moriah E

    2015-04-01

    Early-life trauma is one of the strongest risk factors for later emotional psychopathology. Although research in adults highlights that childhood trauma predicts deficits in emotion regulation that persist decades later, it is unknown whether neural and behavioral changes that may precipitate illness are evident during formative, developmental years. This study examined whether automatic regulation of emotional conflict is perturbed in a high-risk urban sample of trauma-exposed children and adolescents. A total of 14 trauma-exposed and 16 age-, sex-, and IQ-matched comparison youth underwent functional MRI while performing an emotional conflict task that involved categorizing facial affect while ignoring an overlying emotion word. Engagement of the conflict regulation system was evaluated at neural and behavioral levels. Results showed that trauma-exposed youth failed to dampen dorsolateral prefrontal cortex activity and engage amygdala-pregenual cingulate inhibitory circuitry during the regulation of emotional conflict, and were less able to regulate emotional conflict. In addition, trauma-exposed youth showed greater conflict-related amygdala reactivity that was associated with diminished levels of trait reward sensitivity. These data point to a trauma-related deficit in automatic regulation of emotional processing, and increase in sensitivity to emotional conflict in neural systems implicated in threat detection. Aberrant amygdala response to emotional conflict was related to diminished reward sensitivity that is emerging as a critical stress-susceptibility trait that may contribute to the emergence of mental illness during adolescence. These results suggest that deficits in conflict regulation for emotional material may underlie heightened risk for psychopathology in individuals that endure early-life trauma. PMID:25413183

  6. Childhood Trauma Exposure Disrupts the Automatic Regulation of Emotional Processing

    PubMed Central

    Marusak, Hilary A; Martin, Kayla R; Etkin, Amit; Thomason, Moriah E

    2015-01-01

    Early-life trauma is one of the strongest risk factors for later emotional psychopathology. Although research in adults highlights that childhood trauma predicts deficits in emotion regulation that persist decades later, it is unknown whether neural and behavioral changes that may precipitate illness are evident during formative, developmental years. This study examined whether automatic regulation of emotional conflict is perturbed in a high-risk urban sample of trauma-exposed children and adolescents. A total of 14 trauma-exposed and 16 age-, sex-, and IQ-matched comparison youth underwent functional MRI while performing an emotional conflict task that involved categorizing facial affect while ignoring an overlying emotion word. Engagement of the conflict regulation system was evaluated at neural and behavioral levels. Results showed that trauma-exposed youth failed to dampen dorsolateral prefrontal cortex activity and engage amygdala–pregenual cingulate inhibitory circuitry during the regulation of emotional conflict, and were less able to regulate emotional conflict. In addition, trauma-exposed youth showed greater conflict-related amygdala reactivity that was associated with diminished levels of trait reward sensitivity. These data point to a trauma-related deficit in automatic regulation of emotional processing, and increase in sensitivity to emotional conflict in neural systems implicated in threat detection. Aberrant amygdala response to emotional conflict was related to diminished reward sensitivity that is emerging as a critical stress-susceptibility trait that may contribute to the emergence of mental illness during adolescence. These results suggest that deficits in conflict regulation for emotional material may underlie heightened risk for psychopathology in individuals that endure early-life trauma. PMID:25413183

  7. Relating climate change policy to poverty policy: assessing the global exposure of the poor to floods and droughts

    NASA Astrophysics Data System (ADS)

    Winsemius, Hessel; Jongman, Brenden; Veldkamp, Ted; Hallegatte, Stéphane; Bangalore, Mook; Ward, Philip

    2016-04-01

    Prior to the COP21 conference in Paris this year, the World Bank published a report called "Shockwaves - Managing the Impacts of Climate Change on Poverty". The report flagged that ending poverty and stabilizing climate change should be jointly tackled and that without a good joint policy, a further 100 million people could become trapped in poverty by 2050. As part of the "Shockwaves" report, we investigated whether low-income households are disproportionately overrepresented in hazard-prone areas compared to households with higher income. Furthermore, the hazardous conditions under which poor households are exposed to now may become worse due to climate change with resulting increases in intensity and frequency of floods and droughts. We also show how the amount of affected people to these natural hazards change in the future if nothing is done. We use recent advances in the global spatial modeling of flood and drought hazard and a large sample of household surveys containing asset and income data to explore the relationships.

  8. Rat- and human-based risk estimates of lung cancer from occupational exposure to poorly-soluble particles: A quantitative evaluation

    NASA Astrophysics Data System (ADS)

    Kuempel, E. D.; Smith, R. J.; Dankovic, D. A.; Stayner, L. T.

    2009-02-01

    In risk assessment there is a need for quantitative evaluation of the capability of animal models to predict disease risks in humans. In this paper, we compare the rat- and human-based excess risk estimates for lung cancer from working lifetime exposures to inhaled poorly-soluble particles. The particles evaluated include those for which long-term dose-response data are available in both species, i.e., coal dust, carbon black, titanium dioxide, silica, and diesel exhaust particulate. The excess risk estimates derived from the rat data were generally lower than those derived from the human studies, and none of the rat- and human-based risk estimates were significantly different (all p-values>0.05). Residual uncertainty in whether the rat-based risk estimates would over- or under-predict the true excess risks of lung cancer from inhaled poorly-soluble particles in humans is due in part to the low power of the available human studies, limited particle size exposure data for humans, and ambiguity about the best animal models and extrapolation methods.

  9. Warm, Humid, and High Sun Exposure Climates are Associated with Poorly Controlled Eczema: PEER (Pediatric Eczema Elective Registry) Cohort, 2004–2012

    PubMed Central

    Sargen, Michael R.; Hoffstad, Ole; Margolis, David J.

    2013-01-01

    Anecdotal reports of children experiencing eczema flares during winter and summer months along with global variation in eczema prevalence has fueled speculation that climate may modulate disease activity. The aim of this study was to determine if long-term weather patterns affect the severity and persistence of eczema symptoms in children. We performed a prospective cohort study of U.S. children (N=5,595) enrolled in PEER (Pediatric Eczema Elective Registry) between 2004 and 2012 to evaluate the effect of climate (daily temperature, daily sun exposure, daily humidity) on the severity of eczema symptoms. Odds ratios were calculated for the patient evaluated outcome of disease control. Multivariate logistic regression modeling adjusting for gender, race, income, and topical medication use demonstrated that higher temperature (OR=0·90, 95% CI: 0·87–0·93, p<0·001) and increased sun exposure (OR=0·93, 95% CI: 0·89–0·98, p=0·009) were associated with poorly controlled eczema. Higher humidity (OR=0·90, 95% CI: 0·812–0.997, p=0·04) was also associated with poorly controlled disease, but the statistical significance of this association was lost in our multivariate analysis (p=0.44). PMID:23774527

  10. Effects of exposure to television advertising for energy-dense/nutrient-poor food on children's food intake and obesity in South Korea.

    PubMed

    Lee, Bora; Kim, Hyogyoo; Lee, Soo-Kyung; Yoon, Jihyun; Chung, Sang-Jin

    2014-10-01

    The aim of this study was to determine the effect of television food advertising on participant food intake and risk of obesity. A total of 2419 children aged 11-13 years were selected from 118 elementary schools in South Korea. All participants completed a self-administered questionnaire with questions about height, weight, television viewing times, food preferences, and food intakes. To estimate actual exposure to food advertising, we asked participants to specify the times at which they usually watched television. We then collected data on the various types of food advertisement broadcast on five different television networks during those viewing times over the course of the previous 7 months. The amount of television watched and exposure to energy-dense/nutrient-poor (EDNP) food advertising were associated with an increased risk of being overweight or obese. Exposure to television advertising for EDNP food was also significantly associated with higher EDNP food preference and intake and lower fruit and vegetable intake. However, these relationships disappeared for all foods after adjusting for the overall amount of television watched. Although it was not possible to conclude that exposure to television advertising for EDNP food was associated with an increased risk of obesity, preference for EDNP foods, or overall food intake due to the strong comprehensive effects of television viewing time, there was a reason to believe the evidence of the effects of advertising in this study. Future longitudinal studies are needed to determine the exclusive effects of exposure to television advertising for EDNP food. PMID:24996594

  11. ALARA and de minimis concepts in regulation of personnel exposure

    SciTech Connect

    Baum, J.W.

    1987-01-01

    The ALARA process should not be limited by a de minimis level on either collective or individual dose, but should be limited or defined by an acceptable discount-rate on future costs and effects, and a monetary value for detriment, to be used in cost-effectiveness or cost-benefit calculations at dose levels well below the regulatory limits. This approach would provide the desired benefit of simplifying the decision process, it makes it more cost effective, and would avoid the inconsistencies of limits on only one of the four parameters of importance in the optimization process. These are average individual effective dose equivalent rate, number of individuals to be included in the summation, years of exposure, and costs, which include costs of analysis to reduce the exposure. This approach emphasizes that these doses to an individual may not be considered trivial by society when given to a very large population, especially if they could easily be avoided. 32 refs., 2 tabs.

  12. Influence of environmental exposure on human epigenetic regulation

    PubMed Central

    Marsit, Carmen J.

    2015-01-01

    Environmental toxicants can alter epigenetic regulatory features such as DNA methylation and microRNA expression. As the sensitivity of epigenomic regulatory features may be greatest during the in utero period, when critical windows are narrow, and when epigenomic profiles are being set, this review will highlight research focused on that period. I will focus on work in human populations, where the impact of environmental toxicants in utero, including cigarette smoke and toxic trace metals such as arsenic, mercury and manganese, on genome-wide, gene-specific DNA methylation has been assessed. In particular, arsenic is highlighted, as this metalloid has been the focus of a number of studies and its detoxification mechanisms are well understood. Importantly, the tissues and cells being examined must be considered in context in order to interpret the findings of these studies. For example, by studying the placenta, it is possible to identify potential epigenetic adaptations of key genes and pathways that may alter the developmental course in line with the developmental origins of health and disease paradigm. Alternatively, studies of newborn cord blood can be used to examine how environmental exposure in utero can impact the composition of cells within the peripheral blood, leading to immunological effects of exposure. The results suggest that in humans, like other vertebrates, there is a susceptibility for epigenomic alteration by the environment during intrauterine development, and this may represent a mechanism of plasticity of the organism in response to its environment as well as a mechanism through which long-term health consequences can be shaped. PMID:25568453

  13. Trauma exposure interacts with impulsivity in predicting emotion regulation and depressive mood

    PubMed Central

    Ceschi, Grazia; Billieux, Joël; Hearn, Melissa; Fürst, Guillaume; Van der Linden, Martial

    2014-01-01

    Background Traumatic exposure may modulate the expression of impulsive behavioral dispositions and change the implementation of emotion regulation strategies associated with depressive mood. Past studies resulted in only limited comprehension of these relationships, especially because they failed to consider impulsivity as a multifactorial construct. Objective Based on Whiteside and Lynam's multidimensional model that identifies four distinct dispositional facets of impulsive-like behaviors, namely urgency, (lack of) premeditation, (lack of) perseverance, and sensation seeking (UPPS), the current study used a sample of community volunteers to investigate whether an interaction exists between impulsivity facets and lifetime trauma exposure in predicting cognitive emotion regulation and depressive mood. Methods Ninety-three adults completed questionnaires measuring lifetime trauma exposure, impulsivity, cognitive emotion regulation, and depressive mood. Results Results showed that trauma-exposed participants with a strong disposition toward urgency (predisposition to act rashly in intense emotional contexts) tended to use fewer appropriate cognitive emotion regulation strategies than other individuals. Unexpectedly, participants lacking in perseverance (predisposition to have difficulties concentrating on demanding tasks) used more appropriate emotion regulation strategies if they had experienced traumatic events during their life than if they had not. Emotion regulation mediated the path between these two impulsivity facets and depressive mood. Conclusions Together, these findings suggest that impulsivity has a differential impact on emotion regulation and depressive mood depending on lifetime exposure to environmental factors, especially traumatic events. PMID:25317255

  14. Postnatal sulfur dioxide exposure reversibly alters parasympathetic regulation of heart rate.

    PubMed

    Woerman, Amanda L; Mendelowitz, David

    2013-08-01

    Perinatal sulfur dioxide exposure disrupts parasympathetic regulation of cardiovascular activity. Here, we examine the relative risks of prenatal versus postnatal exposure to the air pollutant and the reversibility of the cardiovascular effects. Two groups of animals were used for this study. For prenatal exposure, pregnant Sprague-Dawley dams were exposed to 5 parts per million sulfur dioxide for 1 hour daily throughout gestation and with their pups after birth to medical-grade air through 6 days postnatal. For postnatal exposure, dams were exposed to air, and after delivery along with their pups to 5 parts per million sulfur dioxide through postnatal day 6. ECGs were recorded from pups on postnatal day 5 to examine changes in heart rate. Whole-cell patch-clamp electrophysiology was used to examine changes in neurotransmission to cardiac vagal neurons in the nucleus ambiguus on sulfur dioxide exposure. Postnatal sulfur dioxide exposure diminished glutamatergic neurotransmission to cardiac vagal neurons by 40.9% and increased heart rate, whereas prenatal exposure altered neither of these properties. When postnatal exposure concluded on postnatal day 5, excitatory neurotransmission remained decreased through day 6 and returned to basal levels by day 7. ECGs showed that heart rate remained elevated through day 6 and recovered by day 7. On activation of the parasympathetic diving reflex, the response was significantly blunted by postnatal sulfur dioxide exposure through day 7 but recovered by day 8. Postnatal, but not prenatal, exposure to sulfur dioxide can disrupt parasympathetic regulation of cardiovascular activity. Neonates can recover from these effects within 2 to 3 days of discontinued exposure. PMID:23774227

  15. Postnatal Sulfur Dioxide Exposure Reversibly Alters Parasympathetic Regulation of Heart Rate

    PubMed Central

    Woerman, Amanda L.; Mendelowitz, David

    2014-01-01

    Perinatal sulfur dioxide exposure disrupts parasympathetic regulation of cardiovascular activity. Here, we examine the relative risks of prenatal versus postnatal exposure to the air pollutant, and the reversibility of the cardiovascular effects. Two groups of animals were used for this study. For prenatal exposure, pregnant Sprague-Dawley dams were exposed to 5 parts per million sulfur dioxide for 1 hour daily throughout gestation, and with their pups upon birth to medical-grade air through 6 days postnatal. For postnatal exposure, dams were exposed to air, and upon delivery along with their pups to 5 parts per million sulfur dioxide through postnatal day 6. Electrocardiograms were recorded from pups on postnatal day 5 to examine changes in heart rate. Whole-cell patch-clamp electrophysiology was used to examine changes in neurotransmission to cardiac vagal neurons upon sulfur dioxide exposure. Postnatal sulfur dioxide exposure diminished glutamatergic neurotransmission to cardiac vagal neurons by 40.9% and increased heart rate, whereas prenatal exposure altered neither of these properties. When postnatal exposure concluded on postnatal day 5, excitatory neurotransmission remained decreased through day 6, and returned to basal levels by day 7. Electrocardiograms showed that heart rate remained elevated through day 6 and recovered by day 7. Upon activation of the parasympathetic diving reflex, the response was significantly blunted by postnatal sulfur dioxide exposure through day 7 but recovered by day 8. Postnatal, but not prenatal, exposure to sulfur dioxide can disrupt parasympathetic regulation of cardiovascular activity. Neonates can recover from these effects within 2–3 days of discontinued exposure. PMID:23774227

  16. Prenatal nicotine exposure induces poor articular cartilage quality in female adult offspring fed a high-fat diet and the intrauterine programming mechanisms.

    PubMed

    Tie, Kai; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2016-04-01

    Prenatal nicotine exposure (PNE) induces skeletal growth retardation and dyslipidemia in offspring displaying intrauterine growth retardation (IUGR). Cholesterol accumulation resulting from cholesterol efflux dysfunction may reduce the quality of articular cartilage through fetal programming. This study evaluated the quality of articular cartilage of female adult offspring fed a high-fat diet and explored the mechanisms using a rat IUGR model established by the administration of 2.0mg/kg/d of subcutaneous nicotine from gestational days 11-20. The results demonstrated an increased OARSI (Osteoarthritis Research Society International) score and total cholesterol content, decreased serum corticosterone, and increased IGF1 and dyslipidemia with catch-up growth in PNE adult offspring. Cartilage matrix, IGF1 and cholesterol efflux pathway expression were reduced in PNE fetuses and adult offspring. Therefore, PNE induced poor articular cartilage quality in female adult offspring fed a high-fat diet via a dual programming mechanism. PMID:26769161

  17. Family Interactions, Exposure to Violence, and Emotion Regulation: Perceptions of Children and Early Adolescents at Risk

    ERIC Educational Resources Information Center

    Houltberg, Benjamin J.; Henry, Carolyn S.; Morris, Amanda Sheffield

    2012-01-01

    This study examined the protective nature of youth reports of family interactions in relation to perceived exposure to violence and anger regulation in 84 children and early adolescents (mean age of 10.5; 7-15 years old) primarily from ethnic minority groups and living in high-risk communities in a large southwestern city. Path analysis and…

  18. The Association between Prenatal Cocaine Exposure and Physiological Regulation at 13 Months of Age

    ERIC Educational Resources Information Center

    Schuetze, Pamela; Eiden, Rina D.; Danielewicz, Susan

    2009-01-01

    Background: This study examined the association between prenatal cocaine exposure (PCE) and autonomic regulation at 13 months of age. Methods: Measures of respiratory sinus arrhythmia (RSA) were obtained from 156 (79 exposed, and 77 nonexposed) infants during baseline and during tasks designed to elicit positive (PA) and negative affect (NA).…

  19. Determining the impact of prenatal tobacco exposure on self-regulation at 6 months.

    PubMed

    Wiebe, Sandra A; Fang, Hua; Johnson, Craig; James, Karen E; Espy, Kimberly Andrews

    2014-06-01

    Our goal in the present study was to examine the effects of maternal smoking during pregnancy on infant self-regulation, exploring birth weight as a mediator and sex as a moderator of risk. A prospective sample of 218 infants was assessed at 6 months of age. Infants completed a battery of tasks assessing working memory/inhibition, attention, and emotional reactivity and regulation. Propensity scores were used to statistically control for confounding risk factors associated with maternal smoking during pregnancy. After prenatal and postnatal confounds were controlled, prenatal tobacco exposure was related to reactivity to frustration and control of attention during stimulus encoding. Birth weight did not mediate the effect of prenatal exposure but was independently related to reactivity and working memory/inhibition. The effect of tobacco exposure was not moderated by sex. PMID:24512173

  20. The effects of prolonged exposure and sertraline on emotion regulation in individuals with posttraumatic stress disorder.

    PubMed

    Jerud, Alissa B; Pruitt, Larry D; Zoellner, Lori A; Feeny, Norah C

    2016-02-01

    The effects of current posttraumatic stress disorder (PTSD) interventions on emotion regulation are relatively unknown. Many conceptualize PTSD as a disorder of emotion dysregulation, and clinicians often fear that emotion regulation impairments will not change with stand-alone PTSD treatments, particularly for individuals with pre-existing emotion regulation difficulties. The present study examined changes in emotion regulation (expressive suppression, cognitive reappraisal, negative mood regulation) with prolonged exposure (PE) therapy or sertraline, specifically examining whether those with higher pre-existing emotion regulation difficulties improved over treatment on these indices. Individuals with chronic PTSD (N = 200) received 10 weeks of PE or sertraline and were followed through 6-month follow-up. Emotion regulation was assessed at pre- and post-treatment and at 3- and 6-month follow-up. Individuals with poorer initial emotion regulation showed greater improvement on all indices of emotion regulation, regardless of which treatment they received. Changes occurred during active treatment and were maintained over follow-up. These findings have both theoretical and clinical implications, arguing that emotion regulation is not impaired across all individuals with PTSD and that PE and sertraline effectively address emotion regulation difficulties. PMID:26723004

  1. Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation

    SciTech Connect

    Hermsen, Sanne A.B.; Pronk, Tessa E.; Brandhof, Evert-Jan van den; Ven, Leo T.M. van der; Piersma, Aldert H.

    2013-10-01

    The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol and saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomics was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.

  2. Increased synthesis of folate transporters regulates folate transport in conditions of ethanol exposure and folate deficiency.

    PubMed

    Thakur, Shilpa; More, Deepti; Rahat, Beenish; Khanduja, Krishan Lal; Kaur, Jyotdeep

    2016-01-01

    Excessive alcohol consumption and dietary folate inadequacy are the main contributors leading to folate deficiency (FD). The present study was planned to study regulation of folate transport in conditions of FD and ethanol exposure in human embryonic kidney cell line. Also, the reversible nature of effects mediated by ethanol exposure and FD was determined by folate repletion and ethanol removal. For ethanol treatment, HEK293 cells were grown in medium containing 100 mM ethanol, and after treatment, one group of cells was shifted on medium that was free from ethanol. For FD treatment, cells were grown in folate-deficient medium followed by shifting of one group of cells on folate containing medium. FD as well as ethanol exposure resulted in an increase in folate uptake which was due to an increase in expression of folate transporters, i.e., reduced folate carrier, proton-coupled folate transporter, and folate receptor, both at the mRNA and protein level. The effects mediated by ethanol exposure and FD were reversible on removal of treatment. Promoter region methylation of folate transporters remained unaffected after FD and ethanol exposure. As far as transcription rate of folate transporters is concerned, an increase in rate of synthesis was observed in both ethanol exposure and FD conditions. Additionally, mRNA life of folate transporters was observed to be reduced by FD. An increased expression of folate transporters under ethanol exposure and FD conditions can be attributed to enhanced rate of synthesis of folate transporters. PMID:26433955

  3. Effect of low pH exposure on Na(+) regulation in two cichlid fish species of the Amazon.

    PubMed

    Duarte, Rafael M; Ferreira, Marcio S; Wood, Chris M; Val, Adalberto L

    2013-11-01

    We evaluated the effects of acute exposure to low pH on Na(+) regulation in two Amazon cichlids collected from natural ion-poor "blackwaters", angelfish (Pterophyllum scalare) and discus (Symphysodon discus). Na(+) uptake kinetic parameters, unidirectional Na(+) fluxes, and net Cl(-) fluxes were determined at pH6.0 and 3.6. At pH6.0, both species presented low unidirectional Na(+) flux rates, with kinetics showing a relatively low affinity for Na(+) (angelfish Km=79, discus Km=268μmolL(-1)), with similar maximum transport capacities (Jmax~535nmolg(-1)h(-1)). Overall, there appeared to be high sensitivity to inhibition by low pH, yet low intrinsic branchial permeability limiting diffusive ion effluxes, resulting in relatively low net loss rates of Na(+), the same strategy as seen previously in other blackwater cichlids, and very different from the strategy of blackwater characids. At low pH, Na(+) uptake in angelfish was inhibited competitively (increased Km=166μmolL(-1)) and non-competitively (decreased Jmax=106nmolg(-1)h(-1)), whereas in discus, only a decrease in Jmax (112nmolg(-1)h(-1)) was statistically significant. An acute reduction in H(+)-ATPase activity, but not in Na(+)/K(+)-ATPase activity, in the gills of angelfish suggests a possible mechanism for this non-competitive inhibition at low pH. Discus fish were more tolerant to low pH than angelfish, as seen by lesser effects of exposure to pH3.6 on unidirectional Na(+) uptake and efflux rates and net Na(+) and Cl(-) loss rates. Overall, discus are better than angelfish in maintaining ionic balance under acidic, ion-poor conditions. PMID:23911980

  4. Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

    SciTech Connect

    Li, Luchuan; Lv, Bin; Chen, Bo; Guan, Ming; Sun, Yongfeng; Li, Haipeng; Zhang, Binbin; Ding, Changyuan; He, Shan; Zeng, Qingdong

    2015-07-10

    Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.

  5. Di (2-ethylhexyl) phthalate exposure during pregnancy disturbs temporal sex determination regulation in mice offspring.

    PubMed

    Wang, Yongan; Liu, Wei; Yang, Qing; Yu, Mingxi; Zhang, Zhou

    2015-10-01

    Animal researches and clinical studies have supported the relevance between phthalates exposure and testicular dysgenesis syndrome (TDS). These disorders may comprise common origin in fetal life, especially during sex determination and differentiation, where the mechanism remains unclear. The present study evaluated the disturbances in gene regulatory networks of sex determination in fetal mouse by in utero Di (2-ethylhexyl) phthalate (DEHP) exposure. Temporal expression of key sex determination genes were examined during the critical narrow time window, using whole-mount in situ hybridization and quantitative-PCR. DEHP exposure resulted in significant reduction in mRNA of Sry during sex determination from gestation day (GD) 11.0 to 11.5 in male fetal mice, and the increasing of Sry expression to threshold level on GD 11.5 was delayed. Meanwhile, Gadd45g and Gata4, the upstream genes of Sry, and downstream gene Sox9 were also significantly downregulated in expression. In fetal females, the expression of Wnt4 and beta-catenin were up-regulated by DEHP exposure. Taken together, the results suggest that the potential mechanism of gonadal development disorder by DEHP may origin from repression of important male sex determination signaling pathway, involving Gadd45g → Gata4 → Sry → Sox9. The results would promote a better understanding of the association between phthalate esters (PAEs) exposure and the reductive disorder. PMID:26219507

  6. Down-regulation of human leukocyte antigen class I (HLA-I) is associated with poor prognosis in patients with clear cell renal cell carcinoma.

    PubMed

    Yuan, Jinyang; Liu, Sulai; Yu, Qiuxia; Lin, Yang; Bi, Yunke; Wang, Yi; An, Ruihua

    2013-06-01

    Human leukocyte antigen class I (HLA-I) molecules are transmembrane glycoproteins that have been reported to be down-regulated in multiple types of human malignancies, including clear cell renal cell carcinoma (CCRCC). However, only one study has investigated its prognostic value in CCRCC. In the present study, HLA-I protein expression was analyzed in 120 archived, paraffin-embedded CCRCC samples and 10 adjacent normal tissues using immunohistochemistry. The correlation between HLA-I expression and clinicopathological factors was evaluated by the χ(2) test. Patients' overall survival was analyzed by the Kaplan-Meier method. HLA-I down-regulation was observed in 38.3% (46/120) of renal tumor samples, but only in 10% (1/10) of adjacent normal tissues. Statistical analysis showed a significant correlation of HLA-I expression with TNM stage, lymph node metastasis, and Fuhrman grade. Patients with tumors displaying down-regulation of HLA-I showed significantly shorter overall survival (P=0.021, log-rank test). More importantly, multivariate analysis indicated that down-regulation of HLA-I was an independent prognostic factor for CCRCC patients (P=0.033). Overall, our data suggest that HLA-I down-regulation is associated with tumor progression and a poor prognosis in CCRCC patients, and emphasize the importance of HLA-I in natural and therapeutic immune surveillance of patients with CCRCC. PMID:23245688

  7. Overexpression of SPARC correlates with poor prognosis in patients with cervical carcinoma and regulates cancer cell epithelial-mesenchymal transition

    PubMed Central

    SHI, DEHUAN; JIANG, KAN; FU, YING; FANG, RUI; LIU, XI; CHEN, JIE

    2016-01-01

    Secreted protein acidic and rich in cysteine (SPARC) is associated with the progression of numerous types of cancer. However, the role of SPARC in the progression of cervical cancer has not yet been adequately elucidated. In the current study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were employed to evaluate the mRNA and protein expression of SPARC in normal cervical tissue, cervical intraepithelial neoplasia (CIN) and cervical cancer. In addition, three epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and vimentin) were detected by immunohistochemistry in the same specimens, and an enzyme-linked immunosorbent assay was conducted to detect the serum levels of SPARC in patients with cervical neoplasia. In highly invasive subclones of human cervical carcinoma cells, HeLa-1 and SiHa-1, lentiviral transfections were performed and RT-qPCR and western blot were used to investigate the effects of downregulated EGF-containing fibulin-like extracellular matrix protein 1 on the expression of E-cadherin, N-cadherin and vimentin. The results revealed that, in cervical carcinoma tissue, SPARC expression was significantly upregulated in a manner that positively correlated with N-cadherin and vimentin expression, and negatively correlated with E-cadherin expression. SPARC overexpression and high serum levels were significantly associated with the progression of cervical cancer and adverse prognosis of cervical cancer patients. Downregulation of SPARC can markedly reduce the expression of N-cadherin and vimentin and increase the expression of E-cadherin. Thus, overexpression of SPARC is significantly associated with poor prognostic clinicopathological characteristics in cervical carcinoma, and may be important in EMT. The results of the current study suggest that SPARC may be a potential therapeutic option for individuals diagnosed with cervical carcinoma. PMID:27123099

  8. G-CSF regulates macrophage phenotype and associates with poor overall survival in human triple-negative breast cancer

    PubMed Central

    Hollmén, Maija; Karaman, Sinem; Schwager, Simon; Lisibach, Angela; Christiansen, Ailsa J.; Maksimow, Mikael; Varga, Zsuzsanna; Jalkanen, Sirpa; Detmar, Michael

    2016-01-01

    ABSTRACT Tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and a strong infiltration by TAMs has been associated with estrogen receptor (ER)-negative tumors and poor prognosis. However, the molecular mechanisms behind these observations are unclear. We investigated macrophage activation in response to co-culture with several breast cancer cell lines (T47D, MCF-7, BT-474, SKBR-3, Cal-51 and MDA-MB-231) and found that high granulocyte colony-stimulating factor (G-CSF) secretion by the triple-negative breast cancer (TNBC) cell line MDA-MB-231 gave rise to immunosuppressive HLA-DRlo macrophages that promoted migration of breast cancer cells via secretion of TGF-α. In human breast cancer samples (n = 548), G-CSF was highly expressed in TNBC (p < 0.001) and associated with CD163+ macrophages (p < 0.0001), poorer overall survival (OS) (p = 0.021) and significantly increased numbers of TGF-α+ cells. While G-CSF blockade in the 4T1 mammary tumor model promoted maturation of MHCIIhi blood monocytes and TAMs and significantly reduced lung metastasis, anti-CSF-1R treatment promoted MHCIIloF4/80hiMRhi anti-inflammatory TAMs and enhanced lung metastasis in the presence of high G-CSF levels. Combined anti-G-CSF and anti-CSF-1R therapy significantly increased lymph node metastases, possibly via depletion of the so-called “gate-keeper” subcapsular sinus macrophages. These results indicate that G-CSF promotes the anti-inflammatory phenotype of tumor-induced macrophages when CSF-1R is inhibited and therefore caution against the use of M-CSF/CSF-1R targeting agents in tumors with high G-CSF expression. PMID:27141367

  9. Low Expression of DYRK2 (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2) Correlates with Poor Prognosis in Colorectal Cancer.

    PubMed

    Yan, Haiyan; Hu, Kaishun; Wu, Wenjing; Li, Yu; Tian, Huan; Chu, Zhonghua; Koeffler, H Phillip; Yin, Dong

    2016-01-01

    Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) is a member of dual-specificity kinase family, which could phosphorylate both Ser/Thr and Tyr substrates. The role of DYRK2 in human cancer remains controversial. For example, overexpression of DYRK2 predicts a better survival in human non-small cell lung cancer. In contrast, amplification of DYRK2 gene occurs in esophageal/lung adenocarcinoma, implying the role of DYRK2 as a potential oncogene. However, its clinical role in colorectal cancer (CRC) has not been explored. In this study, we analyzed the expression of DYRK2 from Oncomine database and found that DYRK2 level is lower in primary or metastatic CRC compared to adjacent normal colon tissue or non-metastatic CRC, respectively, in 6 colorectal carcinoma data sets. The correlation between DYRK2 expression and clinical outcome in 181 CRC patients was also investigated by real-time PCR and IHC. DYRK2 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues. Functional studies confirmed that DYRK2 inhibited cell invasion and migration in both HCT116 and SW480 cells and functioned as a tumor suppressor in CRC cells. Furthermore, the lower DYRK2 levels were correlated with tumor sites (P = 0.023), advanced clinical stages (P = 0.006) and shorter survival in the advanced clinical stages. Univariate and multivariate analyses indicated that DYRK2 expression was an independent prognostic factor (P < 0.001). Taking all, we concluded that DYRK2 a novel prognostic biomarker of human colorectal cancer. PMID:27532268

  10. Low Expression of DYRK2 (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2) Correlates with Poor Prognosis in Colorectal Cancer

    PubMed Central

    Wu, Wenjing; Li, Yu; Tian, Huan; Chu, Zhonghua; Koeffler, H. Phillip; Yin, Dong

    2016-01-01

    Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) is a member of dual-specificity kinase family, which could phosphorylate both Ser/Thr and Tyr substrates. The role of DYRK2 in human cancer remains controversial. For example, overexpression of DYRK2 predicts a better survival in human non-small cell lung cancer. In contrast, amplification of DYRK2 gene occurs in esophageal/lung adenocarcinoma, implying the role of DYRK2 as a potential oncogene. However, its clinical role in colorectal cancer (CRC) has not been explored. In this study, we analyzed the expression of DYRK2 from Oncomine database and found that DYRK2 level is lower in primary or metastatic CRC compared to adjacent normal colon tissue or non-metastatic CRC, respectively, in 6 colorectal carcinoma data sets. The correlation between DYRK2 expression and clinical outcome in 181 CRC patients was also investigated by real-time PCR and IHC. DYRK2 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues. Functional studies confirmed that DYRK2 inhibited cell invasion and migration in both HCT116 and SW480 cells and functioned as a tumor suppressor in CRC cells. Furthermore, the lower DYRK2 levels were correlated with tumor sites (P = 0.023), advanced clinical stages (P = 0.006) and shorter survival in the advanced clinical stages. Univariate and multivariate analyses indicated that DYRK2 expression was an independent prognostic factor (P < 0.001). Taking all, we concluded that DYRK2 a novel prognostic biomarker of human colorectal cancer. PMID:27532268

  11. Epidermal Growth Factor Receptors with Tyrosine Kinase Domain Mutations Exhibit Reduced Cbl Association, Poor Ubiquitylation, and Down-regulation but Are Efficiently Internalized

    PubMed Central

    Padrón, David; Sato, Mitsuo; Shay, Jerry W.; Gazdar, Adi F.; Minna, John D.; Roth, Michael G.

    2010-01-01

    Some non–small cell lung cancers (NSCLC) with epidermal growth factor receptor (EGFR) tyrosine kinase domain mutations require altered signaling through the EGFR for cell survival and are exquisitely sensitive to tyrosine kinase inhibitors. EGFR down-regulation was impaired in two NSCLCs with EGFR tyrosine kinase domain mutations. The mutant receptors were poorly ubiquitylated and exhibited decreased association with the ubiquitin ligase Cbl. Over-expression of Cbl increased the degradation of EGFR. Treatment with geldanamycin, an inhibitor of the chaperone heat shock protein 90, also increased both wild-type and mutant EGFR degradation without affecting internalization. The down-regulation of the mutant EGFRs was still impaired when they were stably expressed in normal human bronchial epithelial cells. Thus, the mutations that altered signaling also decreased the interaction of EGFRs with the mechanisms responsible for endosomal sorting. PMID:17699773

  12. Positive parenting mitigates the effects of poor self-regulation on BMI trajectories from age 4 to 15 years

    PubMed Central

    Connell, Lauren E.; Francis, Lori A.

    2014-01-01

    Objective This study sought to determine whether parenting style moderated the effects of delay of gratification on BMI trajectories from age 4 to 15 years. Methods Longitudinal data were analyzed on 778 children drawn from the Study of Early Child Care and Youth Development. Parenting style (authoritative, authoritarian, permissive, neglectful) was created from measures of mothers’ sensitivity and expectations for self-control when children were age 4 years. Self-regulation was also measured at 4 years using a well-known delay of gratification protocol. BMI was calculated from measured height and weight at each time point. Mixed modeling was used to test the interaction of parenting styles and ability to delay gratification on BMI trajectories from 4 to 15 years. Results There was a significant interaction effect of parenting and ability to delay on BMI growth from 4 to 15 years for boys. Boys who had authoritarian mothers and failed to delay gratification had a significantly steeper rate of growth in BMI from childhood through adolescence than children in any other parenting x delay group. Conclusions Authoritative and permissive parenting styles were protective against more rapid BMI gains for boys who could not delay gratification. Ability to delay gratification was protective against BMI gains for boys who had parents with authoritarian or neglectful parenting styles. PMID:23977874

  13. Down-regulation of miR-133a as a poor prognosticator in non-small cell lung cancer.

    PubMed

    Wang, Yuzhou; Li, Jinmei; Chen, Hongming; Mo, Yanli; Ye, Haiyin; Luo, Yiping; Guo, Kangwen; Mai, Zongjiong; Zhang, Ying; Chen, Baoying; Zhou, Yijin; Yang, Zhixiong

    2016-10-15

    miR-133a has been demonstrated to play an important role in tumor progression. The aim of present study was to analyze the correlation between miR-133a expression level and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). The expression of miR-133a in 104 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed by qRT-PCR. Here we show that miR-133a was down-regulated in NSCLC. The levels of miR-133a were negatively correlated with the status of N classification (N0-N1 vs. N2-N3, P=0.000), clinical stage (I-II vs. III-IV, P=0.010) and MMP-14 expression (High vs. Low, P=0.012). The patients with low miR-133a expression had shorter survival time than those with high miR-133a expression. Multivariate analysis indicated that the level of miR-133a expression was an independent prognostic indicator (P=0.012) for the survival of patients with NSCLC. In conclusion, decreased expression of miR-133a might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings. PMID:27282282

  14. Borealin/Dasra B is a cell cycle-regulated chromosomal passenger protein and its nuclear accumulation is linked to poor prognosis for human gastric cancer

    SciTech Connect

    Chang, J.-L.; Chen, T.-H.; Wang, C.-F.; Chiang, Y.-H.; Huang, Y.-L.; Wong, F.-H.; Chou, C.-K. . E-mail: ckchou@mail.pmf.org.tw; Chen, C.-M. . E-mail: cmchen@ym.edu.tw

    2006-04-15

    Chromosomal passenger proteins including Aurora B, Survivin, and Borealin/Dasra B, also called CDCA8/FLJ10468, are known to play crucial roles during mitosis and cell division. Inappropriate chromosomal segregation and cell division may cause auneuploidy leading to cancer. However, it is still unclear how the expression of chromosomal passenger proteins may be linked to cancer. In this study, we demonstrated that Borealin is a cell cycle-regulated gene and is upregulated at G2-M phases of the cell cycle. We showed that Borealin interacts with Survivin but not with Aurora B. The interaction domain of Survivin in Borealin was mapped to the N-terminal 92 amino-acid residues of Borealin. To examine the linkage between expression of Borealin and cancer, we performed immunohistochemistry analysis using anti-Borealin specific antibody on the paraffin-embedded gastric cancer tissues. Our results showed that Borealin expression is significantly correlated with Survivin (P = 0.003) and Ki67 (P = 0.007) in gastric cancer. Interestingly, an increased nuclear Borealin level reveals borderline association with a poor survival rate (P = 0.047). Taken together, our results demonstrated that Borealin is a cell cycle-regulated chromosomal passenger protein and its aberrant expression is linked to a poor prognosis for gastric cancer.

  15. Emotion self-regulation and empathy depend upon longer stimulus exposure.

    PubMed

    Ikezawa, Satoru; Corbera, Silvia; Wexler, Bruce E

    2014-10-01

    Observation of others in pain induces positive elevation (pain effect) in late event-related potentials (ERP). This effect is associated with top-down attention regulating processes. It has previously been shown that stimulus exposure duration can affect top-down attentional modulation of response to threat-related stimuli. We investigated the effect of exposure duration on ERP response to others in pain. Two late ERP components, P3 and late positive potentials (LPP), from 18 healthy people were measured while they viewed pictures of hands in painful or neutral situations for either 200 or 500 ms, during two task conditions (pain judgment and counting hands). P3 and LPP pain effects during the pain judgment condition were significantly greater with 500 ms than 200 ms stimulus presentation. Ours is the first study to suggest that engagement of empathy-related self-regulatory processes reflected in late potentials requires longer exposure to the pain-related stimulus. Although this is important information about the relationship between early sensory and subsequent brain processing, and about engagement of self-regulatory processes, the neural basis of this time-dependence remains unclear. It might be important to investigate the relationship between stimulus duration and empathic response in clinical populations where issues of self-regulation, empathic response and speed of information processing exist. PMID:24064924

  16. Extracellular protein disulfide isomerase regulates coagulation on endothelial cells through modulation of phosphatidylserine exposure

    PubMed Central

    Popescu, Narcis I.; Lupu, Cristina

    2010-01-01

    Tissue factor (TF) is the cellular receptor for plasma protease factor VIIa (FVIIa), and the TF-FVIIa complex initiates coagulation in both hemostasis and thrombosis. Cell surface-exposed TF is mainly cryptic and requires activation to fully exhibit the procoagulant potential. Recently, the protein disulfide isomerase (PDI) has been hypothesized to regulate TF decryption through the redox switch of an exposed disulfide in TF extracellular domain. In this study, we analyzed PDI contribution to coagulation using an in vitro endothelial cell model. In this model, extracellular PDI is detected by imaging and flow cytometry. Inhibition of cell surface PDI induces a marked increase in TF procoagulant function, whereas exogenous addition of PDI inhibits TF decryption. The coagulant effects of PDI inhibition were sensitive to annexin V treatment, suggesting exposure of phosphatidylserine (PS), which was confirmed by prothrombinase assays and direct labeling. In contrast, exogenous PDI addition enhanced PS internalization. Analysis of fluorescent PS revealed that PDI affects both the apparent flippase and floppase activities on endothelial cells. In conclusion, we identified a new mechanism for PDI contribution to coagulation on endothelial cells, namely, the regulation of PS exposure, where PDI acts as a negative regulator of coagulation. PMID:20448108

  17. Fetal nicotine exposure produces postnatal up-regulation of adenylate cyclase activity in peripheral tissues

    SciTech Connect

    Slotkin, T.A.; Navarro, H.A.; McCook, E.C.; Seidler, F.J. )

    1990-01-01

    Gestational exposure to nicotine has been shown to affect development of noradrenergic activity in both the central and peripheral nervous systems. In the current study, pregnant rats received nicotine infusions of 6 mg/kg/day throughout gestation, administered by osmotic minipump implants. After birth, offspring of the nicotine-infused dams exhibited marked increases in basal adenylate cyclase activity in membranes prepared from kidney and heart, as well as supersensitivity to stimulation by either a {beta}-adrenergic agonist, isoproterenol, or by forskolin. The altered responses were not accompanied by up-regulation of {beta}-adrenergic receptors: in fact, ({sup 125}I)pindolol binding was significantly decreased in the nicotine group. These results indicate that fetal nicotine exposure affects enzymes involved in membrane receptor signal transduction, leading to altered responsiveness independently of changes at the receptor level.

  18. Transcriptional response of stress-regulated genes to industrial effluent exposure in the cockle Cerastoderma glaucum.

    PubMed

    Karray, Sahar; Tastard, Emmanuelle; Moreau, Brigitte; Delahaut, Laurence; Geffard, Alain; Guillon, Emmanuel; Denis, Françoise; Hamza-Chaffai, Amel; Chénais, Benoît; Marchand, Justine

    2015-11-01

    This study assessed the responses of molecular biomarkers and heavy metal levels in Cerastoderma glaucum exposed for 1 week to two industrial effluents (1%) discharged into the Tunisian coastal area, F1 and F2, produced by different units of production of a phosphate treatment plant. A significant uptake of metals (Cd, Cu, Zn, and Ni) was observed in exposed cockles compared to controls, with an uptake higher for F1 than for F2. A decrease in LT50 (stress on stress test) was also observed after an exposure to the effluent F1. Treatments resulted in different patterns of messenger RNA (mRNA) expression of the different genes tested in this report. Gene transcription monitoring performed on seven genes potentially involved in the tolerance to metal exposure showed that for both exposures, mechanisms are rapidly and synchronically settled down to prevent damage to cellular components, by (1) handling and exporting out metal ions through the up-regulation of ATP-binding cassette xenobiotic transporter (ABCB1) and metallothionein (MT), (2) increasing the mRNA expression of antioxidant enzymes (catalase (CAT), superoxide dismutases, CuZnSOD and MnSOD), (3) protecting and/or repairing proteins through the expression of heat shock protein 70 (HSP70) mRNAs, and (4) increasing ATP production (through the up-regulation of cytochrome c oxidase 1 (CO1)) to provide energy for cells to tolerate stress exposure. The tools developed may be useful both for future control strategies and for the use of the cockle C. glaucum as a sentinel species. PMID:25613800

  19. Non-coding RNA LINC00857 is predictive of poor patient survival and promotes tumor progression via cell cycle regulation in lung cancer

    PubMed Central

    Wang, Lihui; He, Yanli; Liu, Weijun; Bai, Shengbin; Xiao, Lei; Zhang, Jie; Dhanasekaran, Saravana M.; Wang, Zhuwen; Kalyana-Sundaram, Shanker; Balbin, O. Alejandro; Shukla, Sudhanshu; Lu, Yi; Lin, Jules; Reddy, Rishindra M.; Carrott, Philip W.; Lynch, William R.; Chang, Andrew C.; Chinnaiyan, Arul M.; Beer, David G.; Zhang, Jian; Chen, Guoan

    2016-01-01

    We employed next generation RNA sequencing analysis to reveal dysregulated long non-coding RNAs (lncRNAs) in lung cancer utilizing 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues from 3 separate institutions. We identified 281 lncRNAs with significant differential-expression between LUAD and normal lung tissue. LINC00857, a top deregulated lncRNAs, was overexpressed in tumors and significantly associated with poor survival in LUAD. knockdown of LINC00857 with siRNAs decreased tumor cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth in vivo. Overexpression of LINC00857 increased cancer cell proliferation, colony formation and invasion. Mechanistic analyses indicated that LINC00857 mediates tumor progression via cell cycle regulation. Our study highlights the diagnostic/prognostic potential of LINC00857 in LUAD besides delineating the functional and mechanistic aspects of its aberrant disease specific expression and potentially using as a new therapeutic target. PMID:26862852

  20. Non-coding RNA LINC00857 is predictive of poor patient survival and promotes tumor progression via cell cycle regulation in lung cancer.

    PubMed

    Wang, Lihui; He, Yanli; Liu, Weijun; Bai, Shengbin; Xiao, Lei; Zhang, Jie; Dhanasekaran, Saravana M; Wang, Zhuwen; Kalyana-Sundaram, Shanker; Balbin, O Alejandro; Shukla, Sudhanshu; Lu, Yi; Lin, Jules; Reddy, Rishindra M; Carrott, Philip W; Lynch, William R; Chang, Andrew C; Chinnaiyan, Arul M; Beer, David G; Zhang, Jian; Chen, Guoan

    2016-03-01

    We employed next generation RNA sequencing analysis to reveal dysregulated long non-coding RNAs (lncRNAs) in lung cancer utilizing 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues from 3 separate institutions. We identified 281 lncRNAs with significant differential-expression between LUAD and normal lung tissue. LINC00857, a top deregulated lncRNAs, was overexpressed in tumors and significantly associated with poor survival in LUAD. knockdown of LINC00857 with siRNAs decreased tumor cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth in vivo. Overexpression of LINC00857 increased cancer cell proliferation, colony formation and invasion. Mechanistic analyses indicated that LINC00857 mediates tumor progression via cell cycle regulation. Our study highlights the diagnostic/prognostic potential of LINC00857 in LUAD besides delineating the functional and mechanistic aspects of its aberrant disease specific expression and potentially using as a new therapeutic target. PMID:26862852

  1. Down-regulated expression of the protein-tyrosine phosphatase 1B (PTP1B) is associated with aggressive clinicopathologic features and poor prognosis in hepatocellular carcinoma

    SciTech Connect

    Zheng, Long-Yi; Zhou, Dong-Xun; Lu, Jin; Zhang, Wen-Jun; Zou, Da-Jin

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer PTP1B protein showed decreased expression in 67.79% of the HCC patients. Black-Right-Pointing-Pointer Low PTP1B expression predicts poor prognosis of HCC. Black-Right-Pointing-Pointer Low PTP1B expression is correlated with expansion of OV6{sup +} tumor-initiating cells. Black-Right-Pointing-Pointer Down-regulation of PTP1B is associated with activation of Wnt/{beta}-Catenin signaling. -- Abstract: The protein-tyrosine phosphatase 1B (PTP1B) is a classical non-transmembrane protein tyrosine phosphatase that plays a key role in metabolic signaling and can exert both tumor suppressing and tumor promoting effects in different cancers depending on the substrate involved and the cellular context. However, the expression level and function of PTP1B in hepatocellular carcinoma (HCC) remain unclear. In this study, PTP1B expression was detected by immunohistochemistry in normal liver tissue (n = 16) and hepatocellular carcinoma (n = 169). The correlations between PTP1B expression level and clinicopathologic features and patient survival were also analyzed. One hundred and eleven of 169 HCC patients (65.7%) had negative or low PTP1B expression in tumorous tissues, whereas normal tissues always expressed strong PTP1B. Decreased PTP1B expression was significantly associated with aggressive clinicopathologic features and poor prognosis. Immunohistochemistry also showed that low PTP1B expression level was correlated with high percentage of OV6{sup +} tumor-initiating cells (T-ICs) and high frequency of nuclear {beta}-Catenin expression in HCC specimens. Our findings demonstrate for the first time that the loss of inhibitory effect of PTP1B may contribute to progression and invasion of HCC through activation of Wnt/{beta}-Catenin signaling and expansion of liver T-ICs. PTP1B may serve as a valuable prognostic biomarker and potential therapeutic target in HCC.

  2. Improvement of primary health care of patients with poorly regulated diabetes mellitus type 2 using shared decision-making – the DEBATE trial

    PubMed Central

    2012-01-01

    Background Since 2004, a national Disease Management Program (DMP) has been implemented in Germany, which includes educational measures aimed at patients with type-2 diabetes (T2D). However, about 15-20% of T2D patients remain in poor metabolic control. Qualitative research shows that one reason for this might be an increasing frustration of general practitioners (GPs) with the management of their poorly regulated T2D patients over time. We aim at approaching this problem by improving the GP-patient-communication and fostering shared decision-making. Methods/Design An educative intervention will be tested within a multi-centred cluster-randomized controlled trial (RCT) in Germany. We include 20 GPs in three regions. Each of the 60 GPs will recruit about 13 patients meeting the inclusion criteria (total of 780 patients). GPs allocated to the intervention group will receive a peer-visit from a specifically trained GP-colleague who will motivate them to apply patient-centred communication techniques including patient-centred decision aids. GPs allocated to the control group will not take part in any intervention program, but will provide care as usual to their patients. The primary inclusion criterion for patients at the time of the recruitment is an HbA1c-level of over 8.0. Primary outcome is the change of HbA1c at 6, 12, 18, and 24 months compared to HbA1c at baseline. Secondary outcomes include patient’s participation in the process of shared decision-making and quality of life. Discussion If this intervention proves to be effective it may be integrated into the existing Disease Management Program for T2D in Germany. PMID:22913642

  3. Identification of genes up-regulated in response to Cd exposure in Brassica juncea L.

    PubMed

    Minglin, Lang; Yuxiu, Zhang; Tuanyao, Chai

    2005-12-19

    In this paper, the fluorescent mRNA differential display (DD) technique was applied to analyze transcriptional regulation in response to Cd treatment in a heavy-metal accumulator, Brassica juncea. 154 DD bands were identified, of which fragments corresponding to 15 and 13 cDNAs were successfully cloned from leaves and roots, respectively. Many of the genes were confirmed to have a 2-5 fold increase in expression in both roots and leaves after 48 h Cd exposure (approximately 22.4 ppm). However, several isolated genes, e.g., DD2, DD21, DD22, showed a reversed mRNA expression pattern. Sequencing revealed those Cd-induced up-regulated genes displayed mRNAs corresponding to 19 different genes, 18 of which had a clear identity to Arabidopsis thaliana sequences and a putative function was assigned to 15 of them, including the auxin-responsive GH3, ARF-like small GTPases/ARFs, ARD/ARD', APS reductase, Nop, catalase, zinc finger (C3HC4-type RING finger), diacylglycerol kinase, and haloacid dehalogenase-like hydrolase families. Three cDNAs corresponded to predicted membrane proteins (KOG3491) or a ribosome-associated membrane protein RAMP4. One other clone, DD26, did not show significant identities to any translated sequence in the GenBank database, suggesting it may either encode unidentified proteins, or correspond to un-translated, non-conserved regions of mRNA molecules. These Cd-responsive up-regulated genes are mostly also regulated by abiotic or biotic stresses, e.g., dehydration, chilling, high salt, auxin, heat and infection, in other plants. The present study leads to an increased understanding of genes and/or the biochemical pathways involved in heavy-metal resistance and accumulation in plants. PMID:16226851

  4. Early Life Adverse Environmental Exposures Increase the Risk of Uterine Fibroid Development: Role of Epigenetic Regulation.

    PubMed

    Yang, Qiwei; Diamond, Michael P; Al-Hendy, Ayman

    2016-01-01

    Uterine Fibroids [UF(s), AKA: leiomyoma] are the most important benign neoplastic threat to women's health. They are the most common cause of hysterectomy imposing untold personal consequences and 100s of billions of healthcare dollars, worldwide. Currently, there is no long term effective FDA-approved medical treatment available, and surgery is the mainstay. The etiology of UFs is not fully understood. In this regard, we and others have recently reported that somatic mutations in the gene encoding the transcriptional mediator subunit Med12 are found to occur at a high frequency (∼85%) in UFs. UFs likely originate when a Med12 mutation occurs in a myometrial stem cell converting it into a tumor-forming stem cell leading to a clonal fibroid lesion. Although the molecular attributes underlying the mechanistic formation of UFs is largely unknown, a growing body of literature implicates unfavorable early life environmental exposures as potentially important contributors. Early life exposure to EDCs during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life. Neonatal exposure to the EDCs such as diethylstilbestrol (DES) and genistein during reproductive tract development has been shown to increase the incidence, multiplicity and overall size of UFs in the Eker rat model, concomitantly reprogramming estrogen-responsive gene expression. Importantly, EDC exposure represses enhancer of zeste 2 (EZH2) and reduces levels of histone 3 lysine 27 trimethylation (H3K27me3) repressive mark through Estrogen receptor/Phosphatidylinositide 3-kinases/Protein kinase B non-genomic signaling in the developing uterus. Considering the fact that distinct Mediator Complex Subunit 12 (Med12) mutations are detected in different fibroid lesions in the same uterus, the emergence of each Med12 mutation is likely an independent event in an altered myometrial stem cell. It is therefore possible that a chronic reduction in

  5. Early Life Adverse Environmental Exposures Increase the Risk of Uterine Fibroid Development: Role of Epigenetic Regulation

    PubMed Central

    Yang, Qiwei

    2016-01-01

    Uterine Fibroids [UF(s), AKA: leiomyoma] are the most important benign neoplastic threat to women’s health. They are the most common cause of hysterectomy imposing untold personal consequences and 100s of billions of healthcare dollars, worldwide. Currently, there is no long term effective FDA-approved medical treatment available, and surgery is the mainstay. The etiology of UFs is not fully understood. In this regard, we and others have recently reported that somatic mutations in the gene encoding the transcriptional mediator subunit Med12 are found to occur at a high frequency (∼85%) in UFs. UFs likely originate when a Med12 mutation occurs in a myometrial stem cell converting it into a tumor-forming stem cell leading to a clonal fibroid lesion. Although the molecular attributes underlying the mechanistic formation of UFs is largely unknown, a growing body of literature implicates unfavorable early life environmental exposures as potentially important contributors. Early life exposure to EDCs during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life. Neonatal exposure to the EDCs such as diethylstilbestrol (DES) and genistein during reproductive tract development has been shown to increase the incidence, multiplicity and overall size of UFs in the Eker rat model, concomitantly reprogramming estrogen-responsive gene expression. Importantly, EDC exposure represses enhancer of zeste 2 (EZH2) and reduces levels of histone 3 lysine 27 trimethylation (H3K27me3) repressive mark through Estrogen receptor/Phosphatidylinositide 3-kinases/Protein kinase B non-genomic signaling in the developing uterus. Considering the fact that distinct Mediator Complex Subunit 12 (Med12) mutations are detected in different fibroid lesions in the same uterus, the emergence of each Med12 mutation is likely an independent event in an altered myometrial stem cell. It is therefore possible that a chronic reduction in

  6. Response of extracellular matrix regulators in mouse lung after exposure to photons, protons and simulated solar particle event protons.

    PubMed

    Tian, Jian; Pecaut, Michael J; Coutrakon, George B; Slater, James M; Gridley, Daila S

    2009-07-01

    This study compared the effects of photons (gamma rays), protons and simulated solar particle event protons (sSPE) on the expression of profibrotic factors/extracellular matrix (ECM) regulators in lung tissue after whole-body irradiation. TGF-beta1, matrix metalloproteinase 2 and 9 (MMP-2, -9), and tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1, -2) were assessed on days 4 and 21 in lungs from C57BL/6 mice exposed to 0 Gy or 2 Gy photons (0.7 Gy/min), protons (0.9 Gy/min) and sSPE (0.056 Gy/h). RT-PCR, histological and immunohistochemical techniques were used. The most striking changes included (1) up-regulation of TGF-beta1 by photons and sSPE, but not protons, at both times, (2) MMP-2 enhancement by photons and sSPEs, (3) TIMP-1 up-regulation by photons at both times, and (4) more collagen accumulation after exposure to either photons or sSPE than after exposure to protons. The findings demonstrate that expression of important ECM regulators was highly dependent upon the radiation regimen as well as the time after exposure. The data further suggest that irradiation during an SPE may increase an astronaut's risk for pulmonary complications. The greater perturbations after photon exposure compared to proton exposure have clinical implications and warrant further investigation. PMID:19580505

  7. ADP-ribosylation factor 1 expression regulates epithelial-mesenchymal transition and predicts poor clinical outcome in triple-negative breast cancer

    PubMed Central

    Schlienger, Sabrina; Campbell, Shirley; Pasquin, Sarah; Gaboury, Louis; Claing, Audrey

    2016-01-01

    Metastatic capacities are fundamental features of tumor malignancy. ADP-ribosylation factor (ARF) 1 has emerged as a key regulator of invasion in breast cancer cells. However, the importance of this GTPase, in vivo, remains to be demonstrated. We report that ARF1 is highly expressed in breast tumors of the most aggressive and advanced subtypes. Furthermore, we show that lowered expression of ARF1 impairs growth of primary tumors and inhibits lung metastasis in a murine xenograft model. To understand how ARF1 contributes to invasiveness, we used a poorly invasive breast cancer cell line, MCF7 (ER+), and examined the effects of overexpressing ARF1 to levels similar to that found in invasive cell lines. We demonstrate that ARF1 overexpression leads to the epithelial-mesenchymal transition (EMT). Mechanistically, ARF1 controls cell–cell adhesion through ß-catenin and E-cadherin, oncogenic Ras activation and expression of EMT inducers. We further show that ARF1 overexpression enhances invasion, proliferation and resistance to a chemotherapeutic agent. In vivo, ARF1 overexpressing MCF7 cells are able to form more metastases to the lung. Overall, our findings demonstrate that ARF1 is a molecular switch for cancer progression and thus suggest that limiting the expression/activation of this GTPase could help improve outcome for breast cancer patients. PMID:26908458

  8. ADP-ribosylation factor 1 expression regulates epithelial-mesenchymal transition and predicts poor clinical outcome in triple-negative breast cancer.

    PubMed

    Schlienger, Sabrina; Campbell, Shirley; Pasquin, Sarah; Gaboury, Louis; Claing, Audrey

    2016-03-29

    Metastatic capacities are fundamental features of tumor malignancy. ADP-ribosylation factor (ARF) 1 has emerged as a key regulator of invasion in breast cancer cells. However, the importance of this GTPase, in vivo, remains to be demonstrated. We report that ARF1 is highly expressed in breast tumors of the most aggressive and advanced subtypes. Furthermore, we show that lowered expression of ARF1 impairs growth of primary tumors and inhibits lung metastasis in a murine xenograft model. To understand how ARF1 contributes to invasiveness, we used a poorly invasive breast cancer cell line, MCF7 (ER+), and examined the effects of overexpressing ARF1 to levels similar to that found in invasive cell lines. We demonstrate that ARF1 overexpression leads to the epithelial-mesenchymal transition (EMT). Mechanistically, ARF1 controls cell-cell adhesion through ß-catenin and E-cadherin, oncogenic Ras activation and expression of EMT inducers. We further show that ARF1 overexpression enhances invasion, proliferation and resistance to a chemotherapeutic agent. In vivo, ARF1 overexpressing MCF7 cells are able to form more metastases to the lung. Overall, our findings demonstrate that ARF1 is a molecular switch for cancer progression and thus suggest that limiting the expression/activation of this GTPase could help improve outcome for breast cancer patients. PMID:26908458

  9. Up-regulated expression of scavenger receptor class B type 1 (SR-B1) is associated with malignant behaviors and poor prognosis of breast cancer.

    PubMed

    Li, Juan; Wang, Jing; Li, Ming; Yin, Linlin; Li, Xiang-An; Zhang, Ting-Guo

    2016-06-01

    Scavenger receptor class B type 1 (SR-B1) is an integral membrane protein that is expressed in numerous cells and tissue types. The primary role of SR-B1 is to facilitate uptake of cholesteryl esters from high-density lipoproteins (HDL) in the liver. Altered SR-B1 expression contributes to human diseases. This study assessed association of SR-B1 expression in breast tissue specimens with breast cancer development and prognosis. Tissue specimens from 30 cases of adjacent normal breast tissues, ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDCA) were subjected to Western blot analysis, and 135 cases of DCIS and IDCA were used for quantitative immunohistochemical analysis of SR-B1 expression. The data showed that SR-B1 was significantly overexpressed in IDCA tissues compared to normal breast and DCIS tissues. SR-B1 expression was associated with pre-menopausal status, tumor size, and worse overall survival of patients. The data from this ex vivo study suggests that up-regulated SR-B1 protein expression is associated with malignant behaviors of breast cancer and that SR-B1 is an independent predictor for poor survival in breast cancer patients. PMID:27067809

  10. Exposure to Pre- and Perinatal Risk Factors Partially Explains Mean Differences in Self-Regulation between Races

    PubMed Central

    Barnes, J. C.; Boutwell, Brian B.; Miller, J. Mitchell; DeShay, Rashaan A.; Beaver, Kevin M.; White, Norman

    2016-01-01

    Objectives 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). Methods 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. Results 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. Conclusions 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. PMID:26882110

  11. Chronic Light Exposure in the Middle of the Night Disturbs the Circadian System and Emotional Regulation.

    PubMed

    Ikeno, Tomoko; Yan, Lily

    2016-08-01

    In mammals, the circadian system is composed of a principal circadian oscillator located in the suprachiasmatic nucleus (SCN) and a number of subordinate oscillators in extra-SCN brain regions and peripheral tissues/organs. However, how the time-keeping functions of this multiple oscillator circuit are affected by aberrant lighting environments remains largely unknown. In the present study, we investigated the effects of chronic light exposure in the middle of the night on the circadian system by comparing the mice housed in a 12:4:4:4-h L:DLD condition with the controls in 12:12-h L:D condition. Daily rhythms in locomotor activity were analyzed and the expression patterns of protein products of clock genes Period1 and Period2 (PER1 and PER2) were examined in the SCN and extra-SCN brain regions, including the dorsal striatum, hippocampus, paraventricular nucleus (PVN), and basolateral amygdala (BLA). Following 2 weeks of housing in the L:DLD condition, animals showed disturbed daily rhythms in locomotor activity and lacked daily rhythms of PER1 and PER2 in the SCN. In the extra-SCN brain regions, the PER1 and PER2 rhythms were affected in a region-specific pattern, such that they were relatively undisturbed in the striatum and hippocampus, phase-shifted in the BLA, and abolished in the PVN. In addition, mice in the L:DLD condition showed increased anxiety-like behaviors and reduced brain-derived neurotropic factor messenger RNA expression in the hippocampus, amygdala, and medial prefrontal cortex, which are brain regions that are involved in emotional regulation. These results indicate that nighttime light exposure leads to circadian disturbances not only by abolishing the circadian rhythms in the SCN but also by inducing misalignment among brain oscillators and negatively affects emotional processing. These observations serve to identify risks associated with decisions regarding lifestyle in our modern society. PMID:27075857

  12. Sleep regulation and sex hormones exposure in men and women across adulthood.

    PubMed

    Lord, C; Sekerovic, Z; Carrier, J

    2014-10-01

    This review aims to discuss how endogenous and exogenous testosterone exposures in men and estrogens/progesterone exposures in women interact with sleep regulation. In young men, testosterone secretion peaks during sleep and is linked to sleep architecture. Animal and human studies support the notion that sleep loss suppresses testosterone secretion. Testosterone levels decline slowly throughout the aging process, but relatively few studies investigate its impact on age-related sleep modifications. Results suggest that poorer sleep quality is associated with lower testosterone concentrations and that sleep loss may have a more prominent effect on testosterone levels in older individuals. In women, sex steroid levels are characterized by a marked monthly cycle and reproductive milestones such as pregnancy and menopause. Animal models indicate that estrogens and progesterone influence sleep. Most studies do not show any clear effects of the menstrual cycle on sleep, but sample sizes are too low, and research designs often inhibit definitive conclusions. The effects of hormonal contraceptives on sleep are currently unknown. Pregnancy and the postpartum period are associated with increased sleep disturbances, but their relation to the hormonal milieu still needs to be determined. Finally, studies suggest that menopausal transition and the hormonal changes associated with it are linked to lower subjective sleep quality, but results concerning objective sleep measures are less conclusive. More research is necessary to unravel the effects of vasomotor symptoms on sleep. Hormone therapy seems to induce positive effects on sleep, but key concerns are still unresolved, including the long-term effects and efficacy of different hormonal regimens. PMID:25218407

  13. Poor, Unsafe, and Overweight: The Role of Feeling Unsafe at School in Mediating the Association Among Poverty Exposure, Youth Screen Time, Physical Activity, and Weight Status

    PubMed Central

    Côté-Lussier, Carolyn; Fitzpatrick, Caroline; Séguin, Louise; Barnett, Tracie A.

    2015-01-01

    This study applied socioecological and cumulative risk exposure frameworks to test the hypotheses that 1) the experience of poverty is associated with feeling less safe at school, and 2) feeling less safe is associated with engaging in poorer weight-related behaviors, as well as an increased probability of being overweight or obese. Data were from the ongoing Québec Longitudinal Study of Child Development, initiated in 1998 with a population-based cohort of 2,120 Québec (Canada) infants 5 months of age and their parent or primary caregiver. Measures of youths' (age, 13 years) self-reported feelings of safety, screen time, physical activity, and objectively assessed not overweight/obese (70%), overweight (22%), and obese (8%) weight status were collected in 2011. Family poverty trajectory from birth was assessed by using latent growth modeling. As hypothesized, exposure to poverty was associated with feeling less safe at school and, in turn, with an increased probability of being overweight or obese. The association was most pronounced for youths who experienced chronic poverty. Compared with youths who experienced no poverty and felt unsafe, those who experienced chronic poverty and felt unsafe were nearly 18% more likely to be obese (9.2% vs. 11.2%). Although feeling unsafe was associated with screen time, screen time did not predict weight status. PMID:25921649

  14. Poor, Unsafe, and Overweight: The Role of Feeling Unsafe at School in Mediating the Association Among Poverty Exposure, Youth Screen Time, Physical Activity, and Weight Status.

    PubMed

    Côté-Lussier, Carolyn; Fitzpatrick, Caroline; Séguin, Louise; Barnett, Tracie A

    2015-07-01

    This study applied socioecological and cumulative risk exposure frameworks to test the hypotheses that 1) the experience of poverty is associated with feeling less safe at school, and 2) feeling less safe is associated with engaging in poorer weight-related behaviors, as well as an increased probability of being overweight or obese. Data were from the ongoing Québec Longitudinal Study of Child Development, initiated in 1998 with a population-based cohort of 2,120 Québec (Canada) infants 5 months of age and their parent or primary caregiver. Measures of youths' (age, 13 years) self-reported feelings of safety, screen time, physical activity, and objectively assessed not overweight/obese (70%), overweight (22%), and obese (8%) weight status were collected in 2011. Family poverty trajectory from birth was assessed by using latent growth modeling. As hypothesized, exposure to poverty was associated with feeling less safe at school and, in turn, with an increased probability of being overweight or obese. The association was most pronounced for youths who experienced chronic poverty. Compared with youths who experienced no poverty and felt unsafe, those who experienced chronic poverty and felt unsafe were nearly 18% more likely to be obese (9.2% vs. 11.2%). Although feeling unsafe was associated with screen time, screen time did not predict weight status. PMID:25921649

  15. Noise exposure and hearing loss prevention programmes after 20 years of regulations in the United States

    PubMed Central

    Daniell, W E; Swan, S S; McDaniel, M M; Camp, J E; Cohen, M A; Stebbins, J G

    2006-01-01

    Objectives To evaluate noise exposures and hearing loss prevention efforts in industries with relatively high rates of workers' compensation claims for hearing loss. Methods Washington State workers' compensation records were used to identify up to 10 companies in each of eight industries. Each company (n = 76) was evaluated by a management interview, employee personal noise dosimetry (n = 983), and employee interviews (n = 1557). Results Full‐shift average exposures were ⩾85 dBA for 50% of monitored employees, using Occupational Safety and Health Administration (OSHA) parameters with a 5 dB exchange rate (Lave), but 74% were ⩾85 dBA using a 3 dB exchange rate (Leq). Only 14% had Lave ⩾90 dBA, but 42% had Leq ⩾90 dBA. Most companies conducted noise measurements, but most kept no records, and consideration of noise controls was low in all industries. Hearing loss prevention programmes were commonly incomplete. Management interview scores (higher score = more complete programme) showed significant associations with percentage of employees having Lave ⩾85 dBA and presence of a union (multiple linear regression; R2 = 0.24). Overall, 62% of interviewed employees reported always using hearing protection when exposed. Protector use showed significant associations with percentage of employees specifically required to use protection, management score, and average employee time spent ⩾95 dBA (R2 = 0.65). Conclusions The findings raise serious concerns about the adequacy of prevention, regulation, and enforcement strategies in the United States. The percentage of workers with excessive exposure was 1.5–3 times higher using a 3 dB exchange rate instead of the OSHA specified 5 dB exchange rate. Most companies gave limited or no attention to noise controls and relied primarily on hearing protection to prevent hearing loss; yet 38% of employees did not use protectors routinely. Protector use was highest when hearing loss

  16. Analyses of resected human brain metastases of breast cancer reveal the association between up-regulation of hexokinase 2 and poor prognosis.

    PubMed

    Palmieri, Diane; Fitzgerald, Daniel; Shreeve, S Martin; Hua, Emily; Bronder, Julie L; Weil, Robert J; Davis, Sean; Stark, Andreas M; Merino, Maria J; Kurek, Raffael; Mehdorn, H Maximilian; Davis, Gary; Steinberg, Seth M; Meltzer, Paul S; Aldape, Kenneth; Steeg, Patricia S

    2009-09-01

    Brain metastases of breast cancer seem to be increasingin incidence as systemic therapy improves. Metastatic disease in the brain is associated with high morbidity and mortality. We present the first gene expression analysis of laser-captured epithelial cells from resected human brain metastases of breast cancer compared with unlinked primary breast tumors. The tumors were matched for histology, tumor-node-metastasis stage, and hormone receptor status. Most differentially expressed genes were down-regulated in the brain metastases, which included, surprisingly, many genes associated with metastasis. Quantitative real-time PCR analysis confirmed statistically significant differences or strong trends in the expression of six genes: BMP1, PEDF, LAMgamma3, SIAH, STHMN3, and TSPD2. Hexokinase 2 (HK2) was also of interest because of its increased expression in brain metastases. HK2 is important in glucose metabolism and apoptosis. In agreement with our microarray results, HK2 levels (both mRNA and protein) were elevated in a brain metastatic derivative (231-BR) of the human breast carcinoma cell line MDA-MB-231 relative to the parental cell line (231-P) in vitro. Knockdown of HK2 expression in 231-BR cells using short hairpin RNA reduced cell proliferation when cultures were maintained in glucose-limiting conditions. Finally, HK2 expression was analyzed in a cohort of 123 resected brain metastases of breast cancer. High HK2 expression was significantly associated with poor patient survival after craniotomy (P = 0.028). The data suggest that HK2 overexpression is associated with metastasis to the brain in breast cancer and it may be a therapeutic target. PMID:19723875

  17. Analyses of Resected Human Brain Metastases of Breast Cancer Reveal the Association between Up-regulation of Hexokinase 2 and Poor Prognosis

    PubMed Central

    Palmieri, Diane; Fitzgerald, Daniel; Shreeve, S. Martin; Hua, Emily; Bronder, Julie L.; Weil, Robert J.; Davis, Sean; Stark, Andreas M.; Merino, Maria J.; Kurek, Raffael; Mehdorn, H. Maximilian; Davis, Gary; Steinberg, Seth M.; Meltzer, Paul S.; Aldape, Kenneth; Steeg, Patricia S.

    2009-01-01

    Brain metastases of breast cancer appear to be increasing in incidence as systemic therapy improves. Metastatic disease in the brain is associated with high morbidity and mortality. We present the first gene expression analysis of laser captured epithelial cells from resected human brain metastases of breast cancer compared to unlinked primary breast tumors. The tumors were matched for histology, TNM stage and hormone receptor status. Most differentially expressed genes were down-regulated in the brain metastases which included, surprisingly, many genes associated with metastasis. Q-PCR analysis confirmed statistically significant differences or strong trends in the expression of six genes: BMP1, PEDF, LAMγ3, SIAH, STHMN3 and TSPD2. Hexokinase 2 (HK2) was also of interest because of its increased expression in brain metastases. HK2 is important in glucose metabolism and apoptosis. In agreement with our microarray results, HK2 levels (both mRNA and protein) were elevated in a brain metastatic derivative (231-BR) of the human breast carcinoma cell line MDA-MB-231 relative to the parental cell line (231-P), in vitro. Knockdown of HK2 expression in 231-BR cells using shRNA reduced cell proliferation when cultures were maintained in glucose limiting conditions. Finally, HK2 expression was analyzed in a cohort of 123 resected brain metastases of breast cancer. High HK2 expression was significantly associated with poor patient survival post-craniotomy (P=0.028). The data suggest that HK2 overexpression is associated with metastasis to the brain in breast cancer and it may be a therapeutic target. PMID:19723875

  18. Regulation of arcuate genes by developmental exposures to endocrine-disrupting compounds in female rats.

    PubMed

    Roepke, Troy A; Yang, Jennifer A; Yasrebi, Ali; Mamounis, Kyle J; Oruc, Elif; Zama, Aparna Mahakali; Uzumcu, Mehmet

    2016-07-01

    Developmental exposure to endocrine-disrupting compounds (EDCs) alters reproduction and energy homeostasis, both of which are regulated by the arcuate nucleus (ARC). Little is known about the effects of EDC on ARC gene expression. In Experiment #1, pregnant dams were treated with either two doses of bisphenol A (BPA) or oil from embryonic day (E)18-21. Neonates were injected from postnatal day (PND)0-7. Vaginal opening, body weights, and ARC gene expression were measured. Chrm3 (muscarinic receptor 3) and Adipor1 (adiponectin receptor 1) were decreased by BPA. Bdnf (brain-derived neurotropic factor), Igf1 (insulin-like growth factor 1), Htr2c (5-hydroxytryptamine receptor), and Cck2r (cholescystokinin 2 receptor) were impacted. In Experiment #2, females were exposed to BPA, diethylstilbestrol (DES), di(2-ethylhexyl)phthalate, or methoxychlor (MXC) during E11-PND7. MXC and DES advanced the age of vaginal opening and ARC gene expression was impacted. These data indicate that EDCs alter ARC genes involved in reproduction and energy homeostasis in females. PMID:27103539

  19. Cognitive Emotion Regulation and Written Exposure Therapy for Posttraumatic Stress Disorder

    PubMed Central

    Wisco, Blair E.; Sloan, Denise M.; Marx, Brian P.

    2014-01-01

    We examined the extent to which cognitive emotion-regulation (ER) strategies moderated posttraumatic stress disorder (PTSD) treatment outcome among 40 motor vehicle accident survivors. Participants were randomly assigned to either a brief written exposure therapy (WET) condition or a waitlist condition and were assessed pre- and posttreatment and at a 3-month follow-up. Positive-reappraisal and putting-into-perspective strategies at baseline interacted with condition to predict symptom change over time. Both strategies predicted greater reductions in PTSD in the waitlist group, suggesting facilitation of natural recovery. However, positive reappraisal was associated with smaller reductions in PTSD in the WET group, suggesting that this strategy may interfere with treatment. Treatment also reduced use of the maladaptive ER strategy of rumination. These results provide evidence that putting-into-perspective and positive-reappraisal strategies are beneficial in the absence of treatment and that certain types of ER strategies may reduce response to WET, highlighting the importance of future research examining ER during treatment. PMID:24482755

  20. TEMPERATURE REGULATION IN THE UNRESTRAINED RABBIT DURING EXPOSURE TO 600 MHZ RADIOFREQUENCY RADIATION

    EPA Science Inventory

    Six male New Zealand white rabbits were individually exposed to 600 MHz radiofrequency (RF) radiation for 90 min in a waveguide exposure system at an ambient temperature (Ta) of 20 or 30 C. Immediately after exposure, the rabbit was removed from the exposure chamber and its colon...

  1. Genetical Toxicogenomics in Drosophila Identifies Master Modulatory Loci that are Regulated by Developmental Exposure to Lead

    PubMed Central

    Ruden, Douglas M.; Chen, Lang; Possidente, Debra; Possidente, Bernard; Rasouli, Parsa; Wang, Luan; Lu, Xiangyi; Garfinkel, Mark D.; Hirsch, Helmut V. B.; Page, Grier P.

    2009-01-01

    The genetics of gene expression in recombinant inbred lines (RILs) can be mapped as expression quantitative trait loci (eQTLs). So-called “genetical genomics” studies have identified locally-acting eQTLs (cis-eQTLs) for genes that show differences in steady state RNA levels. These studies have also identified distantly-acting master-modulatory trans-eQTLs that regulate tens or hundreds of transcripts (hotspots or transbands). We expand on these studies by performing genetical genomics experiments in two environments in order to identify trans-eQTL that might be regulated by developmental exposure to the neurotoxin lead. Flies from each of 75 RIL were raised from eggs to adults on either control food (made with 250 µM sodium acetate), or lead-treated food (made with 250 µM lead acetate, PbAc). RNA expression analyses of whole adult male flies (5–10 days old) were performed with Affymetrix DrosII whole genome arrays (18,952 probesets). Among the 1,389 genes with cis-eQTL, there were 405 genes unique to control flies and 544 genes unique to lead-treated ones (440 genes had the same cis-eQTLs in both samples). There are 2,396 genes with trans-eQTL which mapped to 12 major transbands with greater than 95 genes. Permutation analyses of the strain labels but not the expression data suggests that the total number of eQTL and the number of transbands are more important criteria for validation than the size of the transband. Two transbands, one located on the 2nd chromosome and one on the 3rd chromosome, co-regulate 33 lead-induced genes, many of which are involved in neurodevelopmental processes. For these 33 genes, rather than allelic variation at one locus exerting differential effects in two environments, we found that variation at two different loci are required for optimal effects on lead-induced expression. PMID:19737576

  2. Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala.

    PubMed

    Robinson, Stacey L; Alexander, Nancy J; Bluett, Rebecca J; Patel, Sachin; McCool, Brian A

    2016-09-01

    The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol. PMID:26707595

  3. Enhancing offspring hypothalamic-pituitary-adrenal (HPA) regulation via systematic novelty exposure: the influence of maternal HPA function

    PubMed Central

    Dinces, Sarah M.; Romeo, Russell D.; McEwen, Bruce S.; Tang, Akaysha C.

    2014-01-01

    In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother’s ability to mount a rapid corticosterone (CORT) response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring hypothalamic-pituitary-adrenal (HPA) regulation. Using a 2 × 2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel) daily during infancy (PND 1–21) and the other half of the litter remained in the home cage (Neo_Home); we further exposed half of these two groups to early adulthood (PND 54–63) novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB) and the ability to mount a large rapid CORT response (CORTE) to the onset of an acute stressor. Assessment of adult offspring’s ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring’s ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent

  4. CYP2B6*6 genotype and high efavirenz plasma concentration but not nevirapine are associated with low lumefantrine plasma exposure and poor treatment response in HIV-malaria-coinfected patients.

    PubMed

    Maganda, B A; Minzi, O M S; Ngaimisi, E; Kamuhabwa, A A R; Aklillu, E

    2016-02-01

    We investigated the influence of efavirenz (EFV)- or nevirapine (NVP)-based antiretroviral therapy (ART) on lumefantrine plasma exposure in HIV-malaria-coinfected patients and implication of pharmacogenetic variations. A total of 269 HIV patients with uncomplicated falciparum malaria on NVP-based ART (NVP-arm), EFV-based ART (EFV-arm) or not receiving ART (control-arm) were enrolled and treated with artemether-lumefantrine. Day-7 lumefantrine, baseline EFV and NVP plasma concentrations, and CYP2B6*6,*18, CYP3A4*1B, CYP3A5*3,*6,*7, ABCB1 c.3435C>T and ABCB1 c.4036A>G genotypes were determined. The median day-7 lumefantrine plasma concentration was significantly lower in the EFV-arm compared with that in NVP- and control-arm. High EFV plasma concentrations and CYP2B6*6/*6 genotype significantly correlated with low lumefantrine plasma concentrations and high rate of recurrent parasitemia. No significant effect of NVP-based ART on lumefantrine exposure was observed. In conclusion, owing to long-term CYP3A induction, EFV-based ART cotreatment significantly reduces lumefantrine plasma exposure leading to poor malaria treatment response, which is more pronounced in CYP2B6 slow metabolizers. PMID:25963334

  5. Localization, depuration, bioaccumulation and impairment of ion regulation associated with cationic polymer exposure in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Muir, M M; Kosteretz, K G; Lech, J J

    1997-10-01

    1. Static exposure of rainbow trout, Oncorhynchus mykiss, to three commercial 14C-labelled cationic polymers (EDP, epichlorhydrin-dimethylamine; CYT, polyacrylamide ester; and STK, polyacrylamide amide) resulted in 14C being concentrated only in gill tissue. 2. Depuration studies examining the effect of humic acid (HA) on cationic polymer bound in gill tissue indicate that the binding is reversible with exposure to polymer-free water and polymer-free water with HA for each of the three polymers. 3. Analysis of blood pH, Na+, K+, total NH3 and Cl- after static water exposures to EDP (m.w. 50,000) at 7.5 mg EDP/l revealed a treatment related decrease in blood pH, from 7.1 to 6.6, accompanied by an increase in blood NH3 and evidence of severe impairment of ion regulation. 4. Repeated exposure to the cationic polymers did not result in increases in the 14C concentration in gill tissue suggesting that bioaccumulation of the polymers does not occur. 5. These data suggest that the gill is the site of toxicity for these cationic polymers and that their toxic effects involve gill function and ion regulation rather than systemic actions on internal organs. PMID:9364738

  6. RKIP Regulates Neural Cell Apoptosis Induced by Exposure to Microwave Radiation Partly Through the MEK/ERK/CREB Pathway.

    PubMed

    Zuo, Hongyan; Lin, Tao; Wang, Dewen; Peng, Ruiyun; Wang, Shuiming; Gao, Yabing; Xu, Xinping; Zhao, Li; Wang, Shaoxia; Su, Zhentao

    2015-01-01

    In the present study, we investigated whether Raf-1 kinase inhibitory protein (RKIP) is important for neural cell apoptosis induced by microwave exposure and explored the role of MEK/ERK/CREB pathway regulated by RKIP in the apoptosis. Differentiated PC12 cells were exposed to continuous microwave radiation at 2.856 GHz for 5 min with average power density of 30 mW/cm(2). RKIP sense and anti-sense recombinant plasmids were constructed and transfected into PC12 cells, respectively. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay were used to detect cell apoptosis. The results showed that RKIP was downregulated after microwave exposure while the MEK/ERK/CREB signaling pathway was activated excessively. Moreover, the ratio of Bcl-2/Bax decreased, activity of caspase-3 increased, and thus apoptotic DNA fragmentation increased. RKIP overexpression significantly inhibited the phosphorylation of MEK, ERK, and CREB, while RKIP downregulation had the reverse effect. Furthermore, U0126 was found to antagonize the changes caused by RKIP downregulation after exposure to radiation. In conclusion, RKIP plays an important role in the neural cell apoptosis induced by microwave radiation, and the regulation of cell apoptosis by RKIP is partly through the MEK/ERK/CREB pathway. This suggests that RKIP may act as a key regulator of neuronal damage caused by microwave radiation. PMID:25108669

  7. Arsenite exposure accelerates aging process regulated by the transcription factor DAF-16/FOXO in Caenorhabditis elegans.

    PubMed

    Yu, Chan-Wei; How, Chun Ming; Liao, Vivian Hsiu-Chuan

    2016-05-01

    Arsenic is a known human carcinogen and high levels of arsenic contamination in food, soils, water, and air are of toxicology concerns. Nowadays, arsenic is still a contaminant of emerging interest, yet the effects of arsenic on aging process have received little attention. In this study, we investigated the effects and the underlying mechanisms of chronic arsenite exposure on the aging process in Caenorhabditis elegans. The results showed that prolonged arsenite exposure caused significantly decreased lifespan compared to non-exposed ones. In addition, arsenite exposure (100 μM) caused significant changes of age-dependent biomarkers, including a decrease of defecation frequency, accumulations of intestinal lipofuscin and lipid peroxidation in an age-dependent manner in C. elegans. Further evidence revealed that intracellular reactive oxygen species (ROS) level was significantly increased in an age-dependent manner upon 100 μM arsenite exposure. Moreover, the mRNA levels of transcriptional makers of aging (hsp-16.1, hsp-16.49, and hsp-70) were increased in aged worms under arsenite exposure (100 μM). Finally, we showed that daf-16 mutant worms were more sensitive to arsenite exposure (100 μM) on lifespan and failed to induce the expression of its target gene sod-3 in aged daf-16 mutant under arsenite exposure (100 μM). Our study demonstrated that chronic arsenite exposure resulted in accelerated aging process in C. elegans. The overproduction of intracellular ROS and the transcription factor DAF-16/FOXO play roles in mediating the accelerated aging process by arsenite exposure in C. elegans. This study implicates a potential ecotoxicological and health risk of arsenic in the environment. PMID:26796881

  8. Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring.

    PubMed

    Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; van den Hove, Daniel L A

    2016-04-01

    A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague-Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect-related behaviors and their underlying molecular mechanisms. PMID:26844865

  9. Exposure to diesel exhaust up-regulates iNOS expression in ApoE knockout mice

    SciTech Connect

    Bai Ni; Kido, Takashi; Kavanagh, Terrance J.; Kaufman, Joel D.; Rosenfeld, Michael E.; Breemen, Cornelis van; Eeden, Stephan F. van

    2011-09-01

    Traffic related particulate matter air pollution is a risk factor for cardiovascular events; however, the biological mechanisms are unclear. We hypothesize that diesel exhaust (DE) inhalation induces up-regulation of inducible nitric oxide synthase (iNOS), which is known to contribute to vascular dysfunction, progression of atherosclerosis and ultimately cardiovascular morbidity and mortality. Methods: ApoE knockout mice (30-week) were exposed to DE (at 200 {mu}g/m{sup 3} of particulate matter) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week). iNOS expression in the blood vessels and heart was evaluated by immunohistochemistry and western blotting analysis. To examine iNOS activity, thoracic aortae were mounted in a wire myograph, and vasoconstriction stimulated by phenylephrine (PE) was measured with and without the presence of the specific inhibitor for iNOS (1400 W). NF-{kappa}B (p65) activity was examined by ELISA. The mRNA expression of iNOS and NF-{kappa}B (p65) was determined by real-time PCR. Results: DE exposure significantly enhanced iNOS expression in the thoracic aorta (4-fold) and heart (1.5 fold). DE exposure significantly attenuated PE-stimulated vasoconstriction by {approx} 20%, which was partly reversed by 1400 W. The mRNA expression of iNOS and NF-{kappa}B was significantly augmented after DE exposure. NF-{kappa}B activity was enhanced 2-fold after DE inhalation, and the augmented NF-{kappa}B activity was positively correlated with iNOS expression (R{sup 2} = 0.5998). Conclusions: We show that exposure to DE increases iNOS expression and activity possibly via NF-{kappa}B-mediated pathway. We suspect that DE exposure-caused up-regulation of iNOS contributes to vascular dysfunction and atherogenesis, which could ultimately lead to urban air pollution-associated cardiovascular morbidity and mortality. - Highlights: > Exposed ApoE knockout mice (30-week) to diesel exhaust (DE) for 7 weeks. > Examine iNOS expression and activity in the

  10. Maternal distress associates with placental genes regulating fetal glucocorticoid exposure and IGF2: Role of obesity and sex.

    PubMed

    Mina, Theresia H; Räikkönen, Katri; Riley, Simon C; Norman, Jane E; Reynolds, Rebecca M

    2015-09-01

    Maternal emotional distress symptoms, including life satisfaction, anxiety and depressed mood, are worse in Severely Obese (SO) than lean pregnancy and may alter placental genes regulating fetal glucocorticoid exposure and placental growth. We hypothesised that the associations between increased maternal distress symptoms and changes in placental gene expression including IGF2 and genes regulating fetal glucocorticoid exposure are more pronounced in SO pregnancy. We also considered whether there were sex-specific effects. Placental mRNA levels of 11β-HSDs, NR3C1-α, NR3C2, ABC transporters, mTOR and the IGF2 family were measured in term placental samples from 43 lean (BMI≤25kg/m(2)) and 50 SO (BMI≥40kg/m(2)) women, in whom distress symptoms were prospectively evaluated during pregnancy. The mRNA levels of genes with a similar role in regulating fetal glucocorticoid exposure were strongly inter-correlated. Increased maternal distress symptoms associated with increased NR3C2 and IGF2 isoform 1(IGF2-1) in both lean and SO group (p≤0.05). Increased distress was associated with higher ABCB1 and ABCG2 mRNA levels in SO but lower ABCB1 and higher 11β-HSD1 mRNA levels in lean (p≤0.05) suggesting a protective adaptive response in SO placentas. Increased maternal distress associated with reduced mRNA levels of ABCB1, ABCG2, 11β-HSD2, NR3C1-α and IGF2-1 in placentas of female but not male offspring. The observed sex differences in placental responses suggest greater vulnerability of female fetuses to maternal distress with potentially greater fetal glucocorticoid exposure and excess IGF2. Further studies are needed to replicate these findings and to test whether this translates to potentially greater negative outcomes of maternal distress in female offspring in early childhood. PMID:26056743

  11. Down-Regulation of Decapping Protein 2 Mediates Chronic Nicotine Exposure-Induced Locomotor Hyperactivity in Drosophila

    PubMed Central

    Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

    2012-01-01

    Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence. PMID:23300696

  12. Exposure to Diesel Exhaust Up-regulates iNOS Expression in ApoE Knockout Mice

    PubMed Central

    Bai, Ni; Kido, Takashi; Kavanagh, Terrance J.; Kaufman, Joel D.; Rosenfeld, Michael E.; van Breemen, Cornelis; van Eeden, Stephan F.

    2012-01-01

    Traffic related particulate matter air pollution is a risk factor for cardiovascular events; however, the biological mechanisms are unclear. We hypothesize that diesel exhaust (DE) inhalation induces up-regulation of inducible nitric oxide synthase (iNOS), which is known to contribute to vascular dysfunction, progression of atherosclerosis and ultimately cardiovascular morbidity and mortality. Methods ApoE knockout mice (30-week) were exposed to DE (at 200µg/m3 of particulate matter) or filtered-air (control) for 7 weeks (6h/day, 5days/week). iNOS expression in the blood vessels and heart was evaluated by immunohistochemistry and western blotting analysis. To examine iNOS activity, thoracic aortae were mounted in a wire myograph, and vasoconstriction stimulated by phenylephrine (PE) was measured with and without the presence of the specific inhibitor for iNOS (1400W). NF-κB (p65) activity was examined by ELISA. The mRNA expression of iNOS and NF-κB (p65) was determined by real-time PCR. Results DE exposure significantly enhanced iNOS expression in the thoracic aorta (4-fold) and heart (1.5 fold). DE exposure significantly attenuated PE-stimulated vasoconstriction by ~20%, which was partly reversed by 1400W. The mRNA expression of iNOS and NF-κB was significantly augmented after DE exposure. NF-κB activity was enhanced 2-fold after DE inhalation, and the augmented NF-κB activity was positively correlated with iNOS expression (R2= 0.5998). Conclusions We show that exposure to DE increases iNOS expression and activity possibly via NF-κB-mediated pathway. We suspect that DE exposure-caused up-regulation of iNOS contributes to vascular dysfunction and atherogenesis, which could ultimately lead to urban air pollution-associated cardiovascular morbidity and mortality. PMID:21722660

  13. The potential immune modulatory effect of chronic bisphenol A exposure on gene regulation in male medaka (Oryzias latipes) liver.

    PubMed

    Qiu, Wenhui; Shen, Yang; Pan, Chenyuan; Liu, Shuai; Wu, Minghong; Yang, Ming; Wang, Ke-Jian

    2016-08-01

    Bisphenol A (BPA) is a well-known estrogenic endocrine disrupting chemical (EDC) ubiquitously present in various environmental media. The present study aims to identify the responsive genes in male fish chronically exposed to low concentrations of BPA at the transcription level. We screened genes from a suppression subtractive hybridization library constructed from male medaka (Oryzias latipes) livers after 60-d exposure to 10μg/L BPA under the condition at which changes of hepatic antioxidant parameters have been previously reported. The identified genes were predicted to be involved in multiple biological processes including antioxidant physiology, endocrine system, detoxification, notably associated with the immune response processes. With real time PCR analysis, the immune-associated genes including hepcidin-like precursor, complement component and factors, MHC class I, alpha-2-macroglobulin and novel immune-type receptor 6 isoform were significantly up-regulated in a nonmonotonic dose response pattern in livers upon exposure to different concentrations of BPA (0.1, 1, 10, 100, 1000μg/L). Our results demonstrated a negative impact on gene regulation in fish chronically exposed to relatively low and environmentally relevant concentrations of BPA, and suggested the potential immune modulatory effect of chronic EDC exposure on fish. The immunotoxicity of BPA and other EDCs should be much concerned for the health of human beings and other vertebrates exposed to it. PMID:27104808

  14. Influence of short time exposure to an insect growth regulator, hexaflumuron, on mortality and adult emergence of vector mosquitoes.

    PubMed

    Vasuki, V; Rajavel, A R

    1992-01-01

    Hexaflumuron, an insect growth regulator (IGR), was found to greatly affect the development of immatures and emergence of adults of three species of vector mosquitoes, Culex quinquefasciatus, Aedes aegypti and Anopheles stephensi, when larvae were subjected to short time exposure of < or = 1 h. This IGR could completely prevent adult emergence even at a minimum exposure time of 10 min at 0.001, 0.01 and 0.1 mg/l. On treatment, larval and pupal mortality as well as varying degrees of morphogenetic abnormalities were induced in immatures and adults of the three species. Four weeks of control achieved in a slow moving sullage canal breeding Culex quinquefasciatus indicates that this IGR can be of use in such breeding habitats. PMID:1308571

  15. The role of nodose ganglia in the regulation of cardiovascular function following pulmonary exposure to ultraffine titanium dioxide

    PubMed Central

    Kan, Hong; Wu, Zhongxin; Lin, Yen-Chang; Chen, Teh-Hsun; Cumpston, Jared L; Kashon, Michael L; Leonard, Steve; Munson, Albert E; Castranova, Vincent

    2015-01-01

    The inhalation of nanosized air pollutant particles is a recognised risk factor for cardiovascular disease; however, the link between occupational exposure to engineered nanoparticles and adverse cardiovascular events remains unclear. In the present study, the authors demonstrated that pulmonary exposure of rats to ultrafine titanium dioxide (UFTiO2) significantly increased heart rate and depressed diastolic function of the heart in response to isoproterenol. Moreover, pulmonary inhalation of UFTiO2 elevated mean and diastolic blood pressure in response to norepinephrine. Pretreatment of the rats ip with the transient receptor potential (TRP) channel blocker ruthenium red inhibited substance P synthesis in nodose ganglia and associated functional and biological changes in the cardiovascular system. In conclusion, the effects of pulmonary inhalation of UFTiO2 on cardiovascular function are most likely triggered by a lung-nodose ganglia-regulated pathway via the activation of TRP channels in the lung. PMID:23593933

  16. UP-REGULATION OF TISSUE FACTOR IN HUMAN PULMONARY ARTERY ENDOTHELIAL CELLS AFTER ULTRAFINE PARTICLE EXPOSURE

    EPA Science Inventory

    Background: Epidemiology studies have linked exposure to pollutant particles to

    increased cardiovascular mortality and morbidity, but the mechanisms remain unknown.

    Objectives: We tested the hypothesis that the ultrafine fraction of ambient pollutant

    particle...

  17. Epigenetic histone modification regulates developmental lead exposure induced hyperactivity in rats.

    PubMed

    Luo, Man; Xu, Yi; Cai, Rong; Tang, Yuqing; Ge, Meng-Meng; Liu, Zhi-Hua; Xu, Li; Hu, Fan; Ruan, Di-Yun; Wang, Hui-Li

    2014-02-10

    Lead (Pb) exposure was commonly considered as a high environmental risk factor for the development of attention-deficit/hyperactivity disorder (ADHD). However, the molecular basis of this pathological process still remains elusive. In light of the role of epigenetics in modulating the neurological disease and the causative environment, the alterations of histone modifications in the hippocampus of rats exposed by various doses of lead, along with concomitant behavioral deficits, were investigated in this study. According to the free and forced open field test, there showed that in a dosage-dependent manner, lead exposure could result in the increased locomotor activity of rats, that is, hyperactivity: a subtype of ADHD. Western blotting assays revealed that the levels of histone acetylation increased significantly in the hippocampus by chronic lead exposure, while no dramatic changes were detected in terms of expression yields of ADHD-related dopaminergic proteins, indicating that histone acetylation plays essential roles in this toxicant-involved pathogenesis. In addition, the increased level of histone acetylation might be attributed to the enzymatic activity of p300, a typical histone acetyltransferase, as the transcriptional level of p300 was significantly increased upon higher-dose Pb exposure. In summary, this study first discovered the epigenetic mechanism bridging the environmental influence (Pb) and the disease itself (ADHD) in the histone modification level, paving the way for the comprehensive understanding of ADHD's etiology and in further steps, establishing the therapy strategy of this widespread neurological disorder. PMID:24291742

  18. Exposure to coplanar PCBs induces endothelial cell inflammation through epigenetic regulation of NF-κB subunit p65.

    PubMed

    Liu, Dandan; Perkins, Jordan T; Petriello, Michael C; Hennig, Bernhard

    2015-12-15

    Epigenetic modifications of DNA and histones alter cellular phenotypes without changing genetic codes. Alterations of epigenetic marks can be induced by exposure to environmental pollutants and may contribute to associated disease risks. Here we test the hypothesis that endothelial cell dysfunction induced by exposure to polychlorinated biphenyls (PCBs) is mediated in part though histone modifications. In this study, human vascular endothelial cells were exposed to physiologically relevant concentrations of several PCBs congeners (e.g., PCBs 77, 118, 126 and 153) followed by quantification of inflammatory gene expression and changes of histone methylation. Only exposure to coplanar PCBs 77 and 126 induced the expression of histone H3K9 trimethyl demethylase jumonji domain-containing protein 2B (JMJD2B) and nuclear factor-kappa B (NF-κB) subunit p65, activated NF-κB signaling as evidenced by nuclear translocation of p65, and up-regulated p65 target inflammatory genes, such as interleukin (IL)-6, C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and IL-1α/β. The increased accumulation of JMJD2B in the p65 promoter led to a depletion of H3K9me3 repression mark, which accounts for the observed up-regulation of p65 and associated inflammatory genes. JMJD2B gene knockdown confirmed a critical role for this histone demethylase in mediating PCB-induced inflammation of the vascular endothelium. Finally, it was determined, via chemical inhibition, that PCB-induced up-regulation of JMJD2B was estrogen receptor-alpha (ER-α) dependent. These data suggest that coplanar PCBs may exert endothelial cell toxicity through changes in histone modifications. PMID:26519613

  19. Poor Americans: How the Poor White Live.

    ERIC Educational Resources Information Center

    Pilisuk, Marc; Pilisuk, Phyllis

    Contents of this book include the following essays which originally appeared in "Transaction" magazine: (1) "Poor Americans: an introduction," Marc Pilisuk and Phyllis Pilisuk; (2) "How the white poor live," Marc Pilisuk and Phyllis Pilisuk; (3) "The culture of poverty," Oscar Lewis; (4) "Life in Appalachia--the case of Hugh McCaslin," Robert…

  20. Increased expression of long noncoding RNA TUG1 predicts a poor prognosis of gastric cancer and regulates cell proliferation by epigenetically silencing of p57

    PubMed Central

    Zhang, E; He, X; Yin, D; Han, L; Qiu, M; Xu, T; Xia, R; Xu, L; Yin, R; De, W

    2016-01-01

    Recent evidence highlights long noncoding RNAs (lncRNAs) as crucial regulators of cancer biology that contribute to tumorigenesis. LncRNA TUG1 was initially detected in a genomic screen for genes upregulated in response to taurine treatment in developing mouse retinal cells. Our previous study showed that TUG1 could affect cell proliferation through epigenetically regulating HOXB7 in human non-small cell lung cancer. However, the clinical significance and potential role of TUG1 in GC remains unclear. In this study, we found that TUG1 is significantly increased and is correlated with outcomes in gastric cancer (GC). Further experiments revealed that knockdown of TUG1 repressed GC proliferation both in vitro and in vivo. Mechanistic investigations showed that TUG1 has a key role in G0/G1 arrest. We further demonstrated that TUG1 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors, including p15, p16, p21, p27 and p57, thus contributing to the regulation of GC cell cycle and proliferation. Together, our results suggest that TUG1, as a regulator of proliferation, may serve as a candidate prognostic biomarker and target for new therapies in human GC. PMID:26913601

  1. OPIATE EXPOSURE AND WITHDRAWAL DYNAMICALLY REGULATE mRNA EXPRESSION IN THE SEROTONERGIC DORSAL RAPHE NUCLEUS

    PubMed Central

    Lunden, Jason; Kirby, Lynn G.

    2013-01-01

    Previous results from our lab suggest that hypofunctioning of the serotonergic (5-HT) dorsal raphe nucleus (DRN) is involved in stress-induced opiate reinstatement. To further investigate the effects of morphine dependence and withdrawal on the 5-HT DRN system, we measured gene expression at the level of mRNA in the DRN during a model of morphine dependence, withdrawal and post withdrawal stress exposure in rats. Morphine pellets were implanted for 72h and then either removed or animals were injected with naloxone to produce spontaneous or precipitated withdrawal, respectively. Animals exposed to these conditions exhibited withdrawal symptoms including weight loss, wet dog shakes and jumping behavior. Gene expression for brain-derived neurotrophic factor (BDNF), TrkB, corticotrophin releasing-factor (CRF)-R1, CRF-R2, GABAA-α1, μ-opioid receptor (MOR), 5-HT1A, tryptophan hydroxylase2 and the 5-HT transporter was then measured using quantitative real-time PCR at multiple time-points across the model of morphine exposure, withdrawal and post withdrawal stress. Expression levels of BDNF, TrkB and CRF-R1 mRNA were decreased during both morphine exposure and following seven days of withdrawal. CRF-R2 mRNA expression was elevated after seven days of withdrawal. 5-HT1A receptor mRNA expression was decreased following 3 hours of morphine exposure, while TPH2 mRNA expression was decreased after seven days of withdrawal with swim stress. There were no changes in the expression of GABAA-α1, MOR or 5-HT transporter mRNA. Collectively these results suggest that alterations in neurotrophin support, CRF-dependent stress signaling, 5-HT synthesis and release may underlie 5-HT DRN hypofunction that can potentially lead to stress-induced opiate relapse. PMID:24055683

  2. Temperature regulation in the unrestrained rabbit during exposure to 600-MHz radiofrequency radiation

    SciTech Connect

    Gordon, C.J.; Long, M.D.; Fehlner, K.S.

    1986-01-01

    Six male New Zealand white rabbits were individually exposed to 600-MHz radiofrequency (RF) radiation for 90 min in a waveguide exposure system at an ambient temperature (Ta) of 20 or 30 C. Immediately after exposure, the rabbit was removed from the exposure chamber and its colonic and ear skin temperatures were quickly measured. The whole-body specific absorption rate (SAR) required to increase colonic and ear skin temperature was determined. At a Ta of 20 C, the threshold SAR for elevating colonic and ear skin temperature was 0.64 and 0.26 W/kg, respectively. At a Ta of 30 C, the threshold SARs were slightly less than at 20 C, with values of 0.26 W/kg for elevating colonic temperature and 0.19 W/kg for elevating ear skin temperature. The relationship between heat load and elevation in deep body temperature shown in the study at 600 MHz is similar to past studies that employed much-higher frequencies of RF radiation (2450-2884 MHz).

  3. Up-regulation of KIF14 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer.

    PubMed

    Wang, Wenjing; Shi, Yanhua; Li, Jing; Cui, Wei; Yang, Baozhi

    2016-04-01

    Kinesin family member 14 (KIF14) is a member of kinesin family proteins which have been found to be dysregulated in various cancer types. However, the expression of KIF14 and its potential prognostic significance have not been investigated in cervical cancer. Real-time PCR was performed to assess the expression levels of KIF14 in 47 pairs of cervical cancer tissues and their matched normal tissues from patients who had not been exposed to chemotherapy as well as tissue samples from 57 cervical cancer patients who are sensitive to paclitaxel treatment and 53 patients who are resistant. The association between KIF14 expression levels in tissue and clinicopathological features or chemosensitivity was examined. Kaplan-Meier analysis and Cox proportional hazards model were applied to assess the correlation between KIF14 expression levels and overall survival (OS) of cervical cancer patients. KIF14 expression levels were significantly increased in cervical cancer tissues compared with matched non-cancerous tissues and it was higher in tissues of patients who are chemoresistant compared with those who are chemosensitive. KIF14 expression was positively associated with high tumour stage (P=0.0044), lymph node metastasis (P=0.0034) and chemoresistance (P<0.0001). Kaplan-Meier analysis showed that high KIF14 expression levels predicted poor survival in patients with (P=0.0024) or without (P=0.0028) paclitaxel treatment. Multivariate analysis revealed that KIF14 was an independent prognostic factor for OS. Our study suggests that KIF14 may serve as a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer. PMID:27128470

  4. Up-regulation of KIF14 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer

    PubMed Central

    Wang, Wenjing; Shi, Yanhua; Li, Jing; Cui, Wei; Yang, Baozhi

    2016-01-01

    Kinesin family member 14 (KIF14) is a member of kinesin family proteins which have been found to be dysregulated in various cancer types. However, the expression of KIF14 and its potential prognostic significance have not been investigated in cervical cancer. Real-time PCR was performed to assess the expression levels of KIF14 in 47 pairs of cervical cancer tissues and their matched normal tissues from patients who had not been exposed to chemotherapy as well as tissue samples from 57 cervical cancer patients who are sensitive to paclitaxel treatment and 53 patients who are resistant. The association between KIF14 expression levels in tissue and clinicopathological features or chemosensitivity was examined. Kaplan–Meier analysis and Cox proportional hazards model were applied to assess the correlation between KIF14 expression levels and overall survival (OS) of cervical cancer patients. KIF14 expression levels were significantly increased in cervical cancer tissues compared with matched non-cancerous tissues and it was higher in tissues of patients who are chemoresistant compared with those who are chemosensitive. KIF14 expression was positively associated with high tumour stage (P=0.0044), lymph node metastasis (P=0.0034) and chemoresistance (P<0.0001). Kaplan–Meier analysis showed that high KIF14 expression levels predicted poor survival in patients with (P=0.0024) or without (P=0.0028) paclitaxel treatment. Multivariate analysis revealed that KIF14 was an independent prognostic factor for OS. Our study suggests that KIF14 may serve as a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer. PMID:27128470

  5. Analysis of cell-cycle regulation following exposure of lung-derived cells to γ-rays

    NASA Astrophysics Data System (ADS)

    Trani, D.; Lucchetti, C.; Cassone, M.; D'Agostino, L.; Caputi, M.; Giordano, A.

    Acute exposure of mammalian cells to ionizing radiation results in a delay of cell-cycle progression and/or augmentation of apoptosis. Following ionizing radiation-induced DNA damage, cell-cycle arrest in the G1- or G2-phase of the cell-cycle prevents or delays DNA replication or mitosis, providing time for the DNA repair machinery to exert its function. Deregulation or failing of cell-cycle checkpoints and/or DNA repair mechanisms may lead normal cells bearing chromosome mutations to acquire neoplastic autonomy, which in turn can trigger the onset of cancer. Existing studies have focused on the impact of p53 status on the radiation response of lung cancer (LC) cell lines in terms of both cell-cycle regulation and apoptosis, while no comparative studies have been performed on the radiation response of lung derived normal and cancerous epithelial cells. To investigate the radiation response in normal and cancerous phenotypes, along with the role and impact of p53 status, and possible correlations with pRb/p105 or other proteins involved in carcinogenesis and cell-cycle regulation, we selected two lung-derived epithelial cell lines, one normal (NL20, p53 wild-type) and one non-small cell lung cancer (NSCLC), H358 (known to be p53-deficient). We compared the levels of γ-induced cell proliferation ability, cell-cycle arrest, apoptotic index, and expression levels of cell-cycle regulating and regulated proteins. The different cell sensitivity, apoptotic response and protein expression profiles resulting from our study for NL20 and H358 cells suggest that still unknown mechanisms involving p53, pRb/p105 and their target molecules might play a pivotal role in determining cell sensitivity and resistance upon exposure to ionizing radiation.

  6. Regulation of keratin expression by ultraviolet radiation: differential and specific effects of ultraviolet B and ultraviolet a exposure.

    PubMed

    Bernerd, F; Del Bino, S; Asselineau, D

    2001-12-01

    Skin, the most superficial tissue of our body, is the first target of environmental stimuli, among which is solar ultraviolet radiation. Very little is known about the regulation of keratin gene expression by ultraviolet radiation, however, although (i) it is well established that ultraviolet exposure is involved in skin cancers and photoaging and (ii) keratins represent the major epidermal proteins. The aim of this study was to analyze the regulation of human keratin gene expression under ultraviolet B (290-320 nm) or ultraviolet A (320-400 nm) irradiation using a panel of constructs comprising different human keratin promoters cloned upstream of a chloramphenicol acetyl transferase reporter gene and transfected into normal epidermal keratinocytes. By this approach, we demonstrated that ultraviolet B upregulated the transcription of keratin 19 gene and to a lesser extent the keratin 6, keratin 5, and keratin 14 genes. The DNA sequence responsible for keratin 19 induction was localized between -130 and +1. In contrast to ultraviolet B, ultraviolet A irradiation induced only an increase in keratin 17, showing a differential gene regulation between these two ultraviolet ranges. The induction of keratin 19 was confirmed by studying the endogenous protein in keratinocytes in classical cultures as well as in skin reconstructed in vitro and normal human skin. These data show for the first time that keratin gene expression is regulated by ultraviolet radiation at the transcriptional level with a specificity regarding the ultraviolet domain of solar light. PMID:11886503

  7. Systemic TLR2 agonist exposure regulates hematopoietic stem cells via cell-autonomous and cell-non-autonomous mechanisms.

    PubMed

    Herman, A C; Monlish, D A; Romine, M P; Bhatt, S T; Zippel, S; Schuettpelz, L G

    2016-01-01

    Toll-like receptor 2 (TLR2) is a member of the TLR family of receptors that play a central role in innate immunity. In addition to regulating effector immune cells, where it recognizes a wide variety of pathogen-associated and nonpathogen-associated endogenous ligands, TLR2 is expressed in hematopoietic stem cells (HSCs). Its role in HSCs, however, is not well understood. Furthermore, augmented TLR2 signaling is associated with myelodysplastic syndrome, an HSC disorder characterized by ineffective hematopoiesis and a high risk of transformation to leukemia, suggesting that aberrant signaling through this receptor may have clinically significant effects on HSCs. Herein, we show that systemic exposure of mice to a TLR2 agonist leads to an expansion of bone marrow and spleen phenotypic HSCs and progenitors, but a loss of HSC self-renewal capacity. Treatment of chimeric animals shows that these effects are largely cell non-autonomous, with a minor contribution from cell-autonomous TLR2 signaling, and are in part mediated by granulocyte colony-stimulating factor and tumor necrosis factor-α. Together, these data suggest that TLR2 ligand exposure influences HSC cycling and function via unique mechanisms from TLR4, and support an important role for TLR2 in the regulation of HSCs. PMID:27315114

  8. MUSCARINIC CHOLINERGIC RECEPTOR REGULATION AND ACETYLCHOLINESTERASE INHIBITION IN RESPONSE TO INSECTICIDE EXPOSURE DURING DEVELOPMENT

    EPA Science Inventory

    Daily injections of low doses of the organophosphorus pesticide, parathion, into neonatal rats during the rapid phase of cholinergic system development (postnatal days 8-20), resulted in an average 67% inhibition of acetylcholinesterase and a 23% down regulation of muscarinic cho...

  9. Chapter 5. Pesticide Regulations: Exposure-dose modeling from FIFRA to FQPA

    EPA Science Inventory

    The federal laws and regulations governing the registration and use of pesticides in the United States under the Federal Insecticide, Fungicide, and Rodenticide Act are published in the Federal Register, while state laws such as California are published in the California Food an...

  10. Determining the Impact of Prenatal Tobacco Exposure on Self-Regulation at 6 Months

    ERIC Educational Resources Information Center

    Wiebe, Sandra A.; Fang, Hua; Johnson, Craig; James, Karen E.; Espy, Kimberly Andrews

    2014-01-01

    Our goal in the present study was to examine the effects of maternal smoking during pregnancy on infant self-regulation, exploring birth weight as a mediator and sex as a moderator of risk. A prospective sample of 218 infants was assessed at 6 months of age. Infants completed a battery of tasks assessing working memory/inhibition, attention, and…

  11. Sugars and light/dark exposure trigger differential regulation of ADP-glucose pyrophosphorylase genes in Arabidopsis thaliana (thale cress).

    PubMed

    Sokolov, L N; Déjardin, A; Kleczkowski, L A

    1998-12-15

    Expression of four Arabidopsis (thale cress) genes corresponding to the small (ApS) and large subunits (ApL1, ApL2, ApL3) of ADP-glucose pyrophosphorylase (AGPase), a key enzyme of starch biosynthesis, was found to be profoundly and differentially regulated by sugar and light/dark exposures. Transcript levels of both ApL2 and ApL3, and to a lesser extent ApS, increased severalfold upon feeding sucrose or glucose to the detached leaves in the dark, whereas the mRNA content for ApL1 decreased under the same conditions. Glucose was, in general, less effective than sucrose in inducing regulation of AGPase genes, possibly due to observed limitations in its uptake when compared with sucrose uptake by detached leaves. Osmotic agents [sorbitol, poly(ethylene glycol)] had no effect on ApS, ApL2 and ApL3 transcript level, but they did mimic the effect of sucrose on ApL1 gene, suggesting that the latter is regulated by osmotic pressure rather than any particular sugar. For all the genes the sugar effect was closely mimicked by an exposure of the dark-pre-adapted leaves to the light. Under both dark and light conditions, sucrose fed to the detached leaves was found to be rapidly metabolized to hexoses and, to some extent, starch. Starch production reflected most probably an increase in substrate availability for AGPase reaction rather than being due to changes in AGPase protein content, since both the sugar feeding and light exposure had little or no effect on the activity of AGPase or on the levels of its small and large subunit proteins in leaf extracts. The data suggest tight translational or post-translational control, but they may also reflect spatial control of AGPase gene expression within a leaf. The sugar/light-dependent regulation of AGPase gene expression may represent a part of a general cellular response to the availability/allocation of carbohydrates during photosynthesis. PMID:9841881

  12. Down-regulation of C12orf59 is associated with a poor prognosis and VHL mutations in renal cell carcinoma

    PubMed Central

    Wu, Jianting; Li, Cailing; Luo, Liya; Xia, Lingling; Li, Xianxin; Gui, Yaoting; Cai, Zhiming; Li, Zesong

    2016-01-01

    C12orf59 is newly identified gene in kidney. However, the relation of C12orf59 expression and clinic features is unknown. Here, our study showed that C12orf59 was broadly expressed in normal human tissues with high expression levels in kidney while its expression is beyond detectable in a panel of cancer cell lines. C12orf59 expression in RCC was significantly decreased compared with corresponding adjacent noncancerous tissues (P < 0.01). The decreased C12orf59 expression was correlated with lymph node status (P < 0.05), distant metastases (P < 0.05), poor survival (P < 0.001) (HR 3.00; 95% CI, 1.29–7.53), VHL non-sense mutations or frame-shift mutations (P < 0.01), and UMPP gene non-sense mutations or frame-shift mutations (P = 0.01). Thus, we propose that the decreased C12orf59 expression status is a prognostic biomarker of ccRCC and cooperates with the loss of VHL all the while promoting renal carcinogenesis. PMID:26758419

  13. Preparation of a Novel Form of Gelatin With a Three-Dimensional Ordered Macroporous Structure to Regulate the Release of Poorly Water-Soluble Drugs.

    PubMed

    Xu, Jie; Zhao, Zongzhe; Hao, Yanna; Zhao, Ying; Qiu, Yang; Jiang, Jie; Yu, Tong; Ji, Peng; Liu, Ying; Wu, Chao

    2016-09-01

    In this study, a novel three-dimensional ordered macroporous gelatin (3DOMG) was fabricated as a carrier for increasing the solubility of poorly water-soluble drugs, offering sustained release and a high oral bioavailability. Polymethyl methacrylate nanospheres (257 nm) were used as a colloidal plastic framework to synthesize 3DOMG. Fenofibrate (FNB) was selected as a model drug and loaded onto 3DOMG by the adsorption equilibrium method. Detailed characterization showed that the FNB absorbed onto 3DOMG was in a microcrystalline state. A fluorescence experiment and the prepared drug microcrystal network gave further information on the physical state of the drug. A degradation experiment proved that 3DOMG was readily biodegradable. In vitro release testing showed that 3DOMG increased the dissolution rate of FNB and produced a sustained release. An in vivo pharmacokinetic study confirmed that 3DOMG improved the oral bioavailability compared with that of commercial sustained-release capsules. These findings confirm that 3DOMG can be regarded as a promising carrier for an oral drug delivery system. PMID:26906173

  14. Reducing Pb poisoning in birds and Pb exposure in game meat consumers: the dual benefit of effective Pb shot regulation.

    PubMed

    Mateo, Rafael; Vallverdú-Coll, Núria; López-Antia, Ana; Taggart, Mark A; Martínez-Haro, Monica; Guitart, Raimon; Ortiz-Santaliestra, Manuel E

    2014-02-01

    The use of lead (Pb) ammunition in the form of shot pellets has been identified as a Pb exposure risk in wildlife and their human consumers. We explore the hypothesis that Pb shot ban enforcement reduces the risk of avian Pb poisoning as well as Pb exposure in game meat consumers. We assessed compliance with a partial ban on Pb shot commencing in 2003 by examination of 937 waterbirds harvested by hunters between 2007 and 2012 in the Ebro delta (Spain). Prevalence of Pb shot ingestion was determined, as were Pb concentrations in liver and muscle tissue to evaluate the potential for Pb exposure in game meat consumers. Hunted birds with only embedded Pb shot (no steel) declined from 26.9% in 2007-08 to <2% over the following three hunting seasons after ban reinforcement. Pb shot ingestion in mallards decreased from a pre-ban value of 30.2% to 15.5% in the post-ban period. Liver Pb levels were predominantly defined by the presence of ingested shot, whereas muscle levels were defined by the presence of both ingested and embedded shot. Only 2.5% of mallard muscle tissue had Pb levels above European Union regulations for meat (0.1μg/g wet weight) in the 2008-09 season, when Pb shot ingestion prevalence was also at a minimum (5.1%). Effective restrictions in Pb ammunition use have a dual benefit since this reduces Pb exposure for game meat consumers due to embedded ammunition as well as reducing Pb poisoning in waterbirds. PMID:24309467

  15. Regulation of catalase in Neisseria gonorrhoeae. Effects of oxidant stress and exposure to human neutrophils.

    PubMed

    Zheng, H Y; Hassett, D J; Bean, K; Cohen, M S

    1992-09-01

    We studied the effects of oxidant stress on the catalase activity and hydrogen peroxide sensitivity of Neisseria gonorrhoeae. N. gonorrhoeae is an obligate pathogen of man that evokes a remarkable but ineffective neutrophil response. Gonococci make no superoxide dismutase but express high catalase activity. Gonococcal catalase activity increased threefold when organisms were subjected to 1.0 mM hydrogen peroxide. This increase in catalase activity was marked by a parallel increase in protein concentration recognized by a rabbit polyclonal antibody raised against the purified gonococcal enzyme. Catalase was primarily localized to the gonococcal cytoplasm in the presence or absence of stress; only a single isoenzyme of catalase could be identified. Exposure of gonococci to neutrophil-derived oxidants was accomplished by stimulating neutrophils with phorbol myristate acetate or by using gonococcal Opa variants that interacted with neutrophils with different degrees of efficiency. Gonococci exposed to neutrophils demonstrated a twofold increase in catalase activity in spite of some reduction in viability. Exposure of gonococci to 1.0 mM hydrogen peroxide made the organisms significantly more resistant to higher concentrations of hydrogen peroxide and to neutrophils than control organisms. These results suggest that catalase is an important defense for N. gonorrhoeae during attack by human neutrophils. The rapid response of this enzyme to hydrogen peroxide should be taken into consideration in studies designed to evaluate the interaction between neutrophils and gonococci. PMID:1522209

  16. Escherichia coli Response to Uranyl Exposure at Low pH and Associated Protein Regulations

    PubMed Central

    Khemiri, Arbia; Carrière, Marie; Bremond, Nicolas; Ben Mlouka, Mohamed Amine; Coquet, Laurent; Llorens, Isabelle; Chapon, Virginie; Jouenne, Thierry; Cosette, Pascal; Berthomieu, Catherine

    2014-01-01

    Better understanding of uranyl toxicity in bacteria is necessary to optimize strains for bioremediation purposes or for using bacteria as biodetectors for bioavailable uranyl. In this study, after different steps of optimization, Escherichia colicells were exposed to uranyl at low pH to minimize uranyl precipitation and to increase its bioavailability. Bacteria were adapted to mid acidic pH before exposure to 50 or 80 µM uranyl acetate for two hours at pH≈3. To evaluate the impact of uranium, growth in these conditions were compared and the same rates of cells survival were observed in control and uranyl exposed cultures. Additionally, this impact was analyzedby two-dimensional differential gel electrophoresis proteomics to discover protein actors specifically present or accumulated in contact with uranium.Exposure to uranium resulted in differential accumulation of proteins associated with oxidative stress and in the accumulation of the NADH/quinone oxidoreductase WrbA. This FMN dependent protein performs obligate two-electron reduction of quinones, and may be involved in cells response to oxidative stress. Interestingly, this WrbA protein presents similarities with the chromate reductase from E. coli, which was shown to reduce uranyl in vitro. PMID:24587082

  17. Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5.

    PubMed

    Bibb, J A; Chen, J; Taylor, J R; Svenningsson, P; Nishi, A; Snyder, G L; Yan, Z; Sagawa, Z K; Ouimet, C C; Nairn, A C; Nestler, E J; Greengard, P

    2001-03-15

    Cocaine enhances dopamine-mediated neurotransmission by blocking dopamine re-uptake at axon terminals. Most dopamine-containing nerve terminals innervate medium spiny neurons in the striatum of the brain. Cocaine addiction is thought to stem, in part, from neural adaptations that act to maintain equilibrium by countering the effects of repeated drug administration. Chronic exposure to cocaine upregulates several transcription factors that alter gene expression and which could mediate such compensatory neural and behavioural changes. One such transcription factor is DeltaFosB, a protein that persists in striatum long after the end of cocaine exposure. Here we identify cyclin-dependent kinase 5 (Cdk5) as a downstream target gene of DeltaFosB by use of DNA array analysis of striatal material from inducible transgenic mice. Overexpression of DeltaFosB, or chronic cocaine administration, raised levels of Cdk5 messenger RNA, protein, and activity in the striatum. Moreover, injection of Cdk5 inhibitors into the striatum potentiated behavioural effects of repeated cocaine administration. Our results suggest that changes in Cdk5 levels mediated by DeltaFosB, and resulting alterations in signalling involving D1 dopamine receptors, contribute to adaptive changes in the brain related to cocaine addiction. PMID:11268215

  18. Estrogen target gene regulation and coactivator expression in rat uterus after developmental exposure to the ultraviolet filter 4-methylbenzylidene camphor.

    PubMed

    Durrer, Stefan; Maerkel, Kirsten; Schlumpf, Margret; Lichtensteiger, Walter

    2005-05-01

    Because the estrogen receptor (ER) ligand type influences transactivation, it is important to obtain information on molecular actions of nonclassical ER agonists. UV filters from cosmetics represent new classes of endocrine active chemicals, including the preferential ER beta ligands 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor. We studied estrogen target gene expression in uterus of Long Evans rats after developmental exposure to 4-MBC (0.7, 7, 24, and 47 mg/kg x d) administered in feed to the parent generation before mating, during pregnancy and lactation, and to the offspring until adulthood. 4-MBC altered steady-state levels of mRNAs encoding for ER alpha, ER beta, progesterone receptor (PR), IGF-I, androgen receptor, determined by real-time RT-PCR in uterus of 12-wk-old offspring. Western-blot analyses of the same tissue homogenates indicated changes in ER alpha and PR but not ER beta proteins. To assess sensitivity to estradiol (E2), offspring were ovariectomized on d 70, injected with E2 (10 or 50 microg/kg sc) on d 84, and killed 6 h later. Acute up-regulation of PR and IGF-I and down-regulation of ER alpha and androgen receptor by E2 were dose-dependently reduced in 4-MBC-exposed rats. The reduced response to E2 was accompanied by reduced coactivator SRC-1 mRNA and protein levels. Our data indicate that developmental exposure to 4-MBC affects the regulation of estrogen target genes and the expression of nuclear receptor coregulators in uterus at mRNA and protein levels. PMID:15705771

  19. ROR functions as a ceRNA to regulate Nanog expression by sponging miR-145 and predicts poor prognosis in pancreatic cancer

    PubMed Central

    Gao, Song; Wang, Peng; Hua, Yongqiang; Xi, Hao; Meng, Zhiqiang; Liu, Te; Chen, Zhen; Liu, Luming

    2016-01-01

    lncRNAs have emerged as key regulators of tumor development and progression. ROR is a typical lncRNA that plays important regulatory roles in the pathogenesis and progression of tumors. Nevertheless, current understanding of the involvement of ROR in pancreatic adenocarcinoma tumorigenesis remains limited. In this study, we measured ROR in 61 paired cancerous and noncancerous tissue samples by qRT-PCR and investigated the biological role of ROR on the phenotypes of pancreatic cancer stem cells (PCSCs) in vitro and in vivo. The effects of ROR on PCSCs were studied by RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation. The positive ROR/Nanog interaction was identified and verified by immunohistochemistry assay. Compared with adjacent non-tumor tissues, ROR was up-regulated in most tumor tissues. Knockdown of ROR by RNA interference in PCSCs inhibited proliferation, induced apoptosis and decreased migration. Moreover, ROR silencing resulted in significantly decreased tumourigenicity of PCSCs in nude mice than controls. In particular, ROR may act as a ceRNA, effectively becoming a sink for miR-145, thereby activating the derepression of core transcription factors Nanog. In conclusions, we demonstrated that decreased ROR expression could inhibit cell proliferation, invasion, and tumourigenicity by modulating Nanog. Therefore, ROR is a potential novel prognostic marker to predict the clinical outcome of pancreatic cancer patients after surgery and may be a rational target for therapy. PMID:26636540

  20. Combining datasets to predict the effects of regulation of environmental lead exposure in housing stock.

    PubMed

    Strauss, W J; Carroll, R J; Bortnick, S M; Menkedick, J R; Schultz, B D

    2001-03-01

    A model for children's blood lead concentrations as a function of environmental lead exposures was developed by combining two nationally representative sources of data that characterize the marginal distributions of blood lead and environmental lead with a third regional dataset that contains joint measures of blood lead and environmental lead. The complicating factor addressed in this article was the fact that methods for assessing environmental lead were different in the national and regional datasets. Relying on an assumption of transportability (that although the marginal distributions of blood lead and environmental lead may be different between the regional dataset and the nation as a whole, the joint relationship between blood lead and environmental lead is the same), the model makes use of a latent variable approach to estimate the joint distribution of blood lead and environmental lead nationwide. PMID:11252599

  1. Effects of arsenic exposure on DNA methylation and epigenetic gene regulation

    PubMed Central

    Reichard, John F; Puga, Alvaro

    2010-01-01

    Arsenic is a nonmutagenic human carcinogen that induces tumors through unknown mechanisms. A growing body of evidence suggests that its carcinogenicity results from epigenetic changes, particularly in DNA methylation. Changes in gene methylation status, mediated by arsenic, have been proposed activate oncogene expression or silence tumor suppressor genes, leading to long-term changes in activity of genes controlling cell transformation. Mostly descriptive, and often contradictory, studies have demonstrated that arsenic exposure is associated with both hypo- and hyper-methylation at various genetic loci in vivo or in vitro. This ambiguity has made it difficult to assess whether the changes induced by arsenic are causally involved in the transformation process or are simply a reflection of the altered physiology of rapidly dividing cancer cells. Here, we discuss the evidence supporting changes in DNA methylation as a cause of arsenic carcinogenesis and highlight the strengths and limitations of these studies, as well areas where consistencies and inconsistencies exist. PMID:20514360

  2. Sterilizing the Poor

    ERIC Educational Resources Information Center

    Rothman, Sheila M.

    1977-01-01

    Suggests that freedom for the middle classes may mean vulnerability for the poor. The enthusiasm for sterilization may be so intense as to deprive the poor of their right not to be sterilized. (Author/AM)

  3. Gestational nicotine exposure regulates expression of AMPA and NMDA receptors and their signaling apparatus in developing and adult rat hippocampus

    PubMed Central

    Wang, Hong; Dávila-García, Martha I.; Yarl, Weonpo; Gondré-Lewis, Marjorie C.

    2011-01-01

    Untimely activation of nicotinic acetylcholine receptor (nAChR) by nicotine results in short- and long-term consequences on learning and behavior. In this study, the aim was to determine how prenatal nicotine exposure affects components of glutamatergic signaling in the hippocampus during postnatal development. We investigated regulation of both nAChRs and glutamate receptors for α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA), from postnatal day (P) 1 to P63 after a temporally restricted exposure to saline or nicotine for 14 days in utero. We analyzed postsynaptic density components associated with AMPAR and NMDAR signaling: Calcium/calmodulin-dependent protein kinase II α (CaMKIIα), Calmodulin (CaM), and postsynaptic density-95 (PSD95), as well as presynaptically localized synaptosomal-associated protein 25 (SNAP25). At P1, there was significantly heightened expression of AMPAR subunit GluR1 but not GluR2, and of NMDAR subunits NR1, NR2a and NR2d but not NR2b. NR2c was not detectable. At P1, the postsynaptic proteins CaMKIIα, CaM, and PSD95 were also significantly upregulated, together with presynaptic SNAP25. This enhanced expression of glutamate receptors and signaling proteins was concomitant with elevated levels of [3H] Epibatidine (EB) binding in prenatal nicotine-exposed hippocampus, indicating that α4β2 nAChR may influence glutamatergic function in the hippocampus at P1. By P14, neither [3H]EB binding nor the expression levels of subunits GluR1, GluR2, NR1, NR2a, NR2b, NR2c, or NR2d seemed changed with prenatal nicotine. However, CaMKIIα was significantly upregulated with nicotine treatment while CaM showed downregulation at P14. The effects of nicotine persisted in young adult brains at P63. They exhibited significantly downregulated GluR2, NR1, and NR2c expression levels in hippocampal homogenates and a considerably muted overall distribution of [3H]AMPA binding in areas CA1, CA2, CA3, and the dentate

  4. Effects of sodium chloride exposure on ion regulation in larvae (glochidia) of the freshwater mussel Lampsilis fasciola.

    PubMed

    Nogueira, Lygia S; Bianchini, Adalto; Wood, Chris M; Loro, Vania L; Higgins, Sarah; Gillis, Patricia L

    2015-12-01

    The salinization of freshwater can have negative effects on ecosystem health, with heightened effects in salt-sensitive biota such as glochidia, the larvae of freshwater mussels. However, the toxicological mechanism underlying this sensitivity is unknown. Therefore, Lampsilis fasciola glochidia were exposed to NaCl (nominally 0.25 and 1.0 g/L) prepared in reconstituted moderately-hard water (control), as well as to a dilution of that water (1:4) with ultrapure reference water (diluted control). Unidirectional Na(+) influx (measured with (22)Na) was evaluated after 1, 3 and 48 h of exposure. In addition, unidirectional Cl(-) influx (measured with (36)Cl), whole-body ion (Cl(-) and Na(+)) concentrations, and glochidia viability (measured as the ability to close valves) were assessed after 48 h of exposure. Significantly reduced glochidia viability (56%) was observed after exposure to 1.0 g/L NaCl. Na(+) influx was significantly higher in glochidia exposed to both 0.25 and 1.0 g/L NaCl for 1h than in those kept under control conditions. After 3 and 48 h of exposure, differences in Na(+) influx rate between salt-exposed and control glochidia were generally reduced, indicating that larvae may be able to, at least temporarily, recover their ability to regulate Na(+) influx when exposed to elevated NaCl concentration. Compared to the moderately-hard water control, whole-body Na(+) and Cl(-) concentrations were relatively unchanged in glochidia exposed to 0.25 g/L NaCl, but were significantly elevated in glochidia exposed to 1.0 g/L NaCl and the diluted control. While Na(+) influx rate had recovered to the control level after 48 h of exposure to 1.0 g/L NaCl, Cl(-) influx rate remained elevated, being ~7-fold higher than the Na(+) influx rate. These findings suggest that the loss of viability observed when glochidia were exposed to a high NaCl concentration (1.0 g/L) could be caused by ionoregulatory disturbances mainly associated with an elevated Cl(-) influx. PMID

  5. Fluoride exposure regulates the elongation phase of protein synthesis in cultured Bergmann glia cells.

    PubMed

    Flores-Méndez, Marco; Ramírez, Diana; Alamillo, Nely; Hernández-Kelly, Luisa C; Del Razo, Luz María; Ortega, Arturo

    2014-08-17

    Fluoride is an environmental pollutant present in dental products, food, pesticides and water. The latter, is the greatest source of exposure to this contaminant. Structural and functional damages to the central nervous system are present in exposed population. An established consequence of the neuronal is the release of a substantial amount of glutamate to the extracellular space, leading to an excitotoxic insult. Glutamate exerts its actions through the activation of specific plasma membrane receptors and transporters present in neurons and in glia cells and it is the over-activation of glutamate receptors and transporters, the biochemical hallmark of neuronal and oligodendrocyte cell death. In this context, taking into consideration that fluoride leads to degeneration of cerebellar cells, we took the advantage of the well-established model of cerebellar Bergmann glia cultures to gain insight into the molecular mechanisms inherent to fluoride neurotoxicity that might be triggered in glia cells. We could establish that fluoride decreases [(35)S]-methionine incorporation into newly synthesized polypeptides, in a time-dependent manner, and that this halt in protein synthesis is the result of a decrease in the elongation phase of translation, mediated by an augmentation of eukaryotic elongation factor 2 phosphorylation. These results favor the notion of glial cells as targets of fluoride toxicity and strengthen the idea of a critical involvement of glia cells in the function and dysfunction of the brain. PMID:24954634

  6. Up-regulated expression of phospholipase C, β1 is associated with tumor cell proliferation and poor prognosis in hepatocellular carcinoma

    PubMed Central

    Li, Junxiang; Zhao, Xuya; Wang, Dazhi; He, Wei; Zhang, Shuai; Cao, Wei; Huang, Yu; Wang, Ling; Zhou, Shi; Luo, Kaijian

    2016-01-01

    Background Phospholipase C, β1 (PLCB1) plays critical roles in intracellular transduction and regulating signal activation which are important to tumorigenesis. However, the mechanism of PLCB1 in hepatocellular carcinoma (HCC) is still unknown. This study aims to investigate whether its expression is associated with the clinicopathological parameters and prognosis of the patients with HCC. Methods Immunohistochemistry on two tissue microarrays containing 141 cases of HCC tissues and adjacent non-tumorous tissues were performed to analyze the correlation between PLCB1 expression and clinicopathological features. Kaplan–Meier analysis and Cox multivariate analysis were performed to determine the PLCB1 expression in HCC prognosis. Furthermore, effects of PLCB1 on proliferation of HCC cells were explored using a colony formation assay and apoptosis assay. Results We identified that PLCB1 expression was significantly higher in tumor tissues than that in adjacent non-tumorous tissues and associated with advanced tumor stage. Kaplan–Meier survival analysis showed that patients with PLCB1-positive tumors had poorer survival than the patients with PLCB1-negative tumors. In multivariate analyses, PLCB1 expression was an independent prognostic factor. Moreover, overexpression of PLCB1 in HCC cells promoted cell proliferation and inhibited apoptosis, while knocking down PLCB1 reduced cell viability in vitro. Further investigation found that activation of ERK signaling might involve in PLCB1-mediated cell growth. Conclusion Our study suggests that PLCB1 promotes the progression of HCC and can be served as an independent prognostic factor and a promising therapeutic target in HCC. PMID:27051304

  7. PIAS1 is a determinant of poor survival and acts as a positive feedback regulator of AR signaling through enhanced AR stabilization in prostate cancer

    PubMed Central

    Puhr, M; Hoefer, J; Eigentler, A; Dietrich, D; van Leenders, G; Uhl, B; Hoogland, M; Handle, F; Schlick, B; Neuwirt, H; Sailer, V; Kristiansen, G; Klocker, H; Culig, Z

    2016-01-01

    Novel drugs like Abiraterone or Enzalutamide, which target androgen receptor (AR) signaling to improve androgen deprivation therapy (ADT), have been developed during the past years. However, the application of these drugs is limited because of occurrence of inherent or acquired therapy resistances during the treatment. Thus, identification of new molecular targets is urgently required to improve current therapeutic prostate cancer (PCa) treatment strategies. PIAS1 (protein inhibitor of activated STAT1 (signal transducer and activator of transcription-1)) is known to be an important cell cycle regulator and PIAS1-mediated SUMOylation is essential for DNA repair. In this context, elevated PIAS1 expression has already been associated with cancer initiation. Thus, in the present study, we addressed the question of whether PIAS1 targeting can be used as a basis for an improved PCa therapy in combination with anti-androgens. We show that PIAS1 significantly correlates with AR expression in PCa tissue and in cell lines and demonstrate that high PIAS1 levels predict shorter relapse-free survival. Our patient data are complemented by mechanistic and functional in vitro experiments that identify PIAS1 as an androgen-responsive gene and a crucial factor for AR signaling via prevention of AR degradation. Furthermore, PIAS1 knockdown is sufficient to decrease cell proliferation as well as cell viability. Strikingly, Abiraterone or Enzalutamide treatment in combination with PIAS1 depletion is even more effective than single-drug treatment in multiple PCa cell models, rendering PIAS1 as a promising target protein for a combined treatment approach to improve future PCa therapies. PMID:26257066

  8. PIAS1 is a determinant of poor survival and acts as a positive feedback regulator of AR signaling through enhanced AR stabilization in prostate cancer.

    PubMed

    Puhr, M; Hoefer, J; Eigentler, A; Dietrich, D; van Leenders, G; Uhl, B; Hoogland, M; Handle, F; Schlick, B; Neuwirt, H; Sailer, V; Kristiansen, G; Klocker, H; Culig, Z

    2016-05-01

    Novel drugs like Abiraterone or Enzalutamide, which target androgen receptor (AR) signaling to improve androgen deprivation therapy (ADT), have been developed during the past years. However, the application of these drugs is limited because of occurrence of inherent or acquired therapy resistances during the treatment. Thus, identification of new molecular targets is urgently required to improve current therapeutic prostate cancer (PCa) treatment strategies. PIAS1 (protein inhibitor of activated STAT1 (signal transducer and activator of transcription-1)) is known to be an important cell cycle regulator and PIAS1-mediated SUMOylation is essential for DNA repair. In this context, elevated PIAS1 expression has already been associated with cancer initiation. Thus, in the present study, we addressed the question of whether PIAS1 targeting can be used as a basis for an improved PCa therapy in combination with anti-androgens. We show that PIAS1 significantly correlates with AR expression in PCa tissue and in cell lines and demonstrate that high PIAS1 levels predict shorter relapse-free survival. Our patient data are complemented by mechanistic and functional in vitro experiments that identify PIAS1 as an androgen-responsive gene and a crucial factor for AR signaling via prevention of AR degradation. Furthermore, PIAS1 knockdown is sufficient to decrease cell proliferation as well as cell viability. Strikingly, Abiraterone or Enzalutamide treatment in combination with PIAS1 depletion is even more effective than single-drug treatment in multiple PCa cell models, rendering PIAS1 as a promising target protein for a combined treatment approach to improve future PCa therapies. PMID:26257066

  9. Chronic fetal exposure to caffeine altered resistance vessel functions via RyRs-BKCa down-regulation in rat offspring

    PubMed Central

    Li, Na; Li, Yongmei; Gao, Qinqin; Li, Dawei; Tang, Jiaqi; Sun, Miao; Zhang, Pengjie; Liu, Bailin; Mao, Caiping; Xu, Zhice

    2015-01-01

    Caffeine modifies vascular/cardiac contractility. Embryonic exposure to caffeine altered cardiac functions in offspring. This study determined chronic influence of prenatal caffeine on vessel functions in offspring. Pregnant Sprague-Dawley rats (5-month-old) were exposed to high dose of caffeine, their offspring (5-month-old) were tested for vascular functions in mesenteric arteries (MA) and ion channel activities in smooth muscle cells. Prenatal exposure to caffeine increased pressor responses and vasoconstrictions to phenylephrine, accompanied by enhanced membrane depolarization. Large conductance Ca2+-activated K+ (BKCa) channels in buffering phenylephrine-induced vasoconstrictions was decreased, whole cell BKCa currents and spontaneous transient outward currents (STOCs) were decreased. Single channel recordings revealed reduced voltage/Ca2+ sensitivity of BKCa channels. BKCa α-subunit expression was unchanged, BKCa β1-subunit and sensitivity of BKCa to tamoxifen were reduced in the caffeine offspring as altered biophysical properties of BKCa in the MA. Simultaneous [Ca2+]i fluorescence and vasoconstriction testing showed reduced Ca2+, leading to diminished BKCa activation via ryanodine receptor Ca2+ release channels (RyRs), causing enhanced vascular tone. Reduced RyR1 was greater than that of RyR3. The results suggest that the altered STOCs activity in the caffeine offspring could attribute to down-regulation of RyRs-BKCa, providing new information for further understanding increased risks of hypertension in developmental origins. PMID:26277840

  10. Aniline exposure associated with up-regulated transcriptional responses of three glutathione S-transferase Delta genes in Drosophila melanogaster.

    PubMed

    Chan, Wen-Chiao; Chien, Yi-Chih; Chien, Cheng-I

    2015-03-01

    Complex transcriptional profile of glutathione S-transferase Delta cluster genes occurred in the developmental process of the fruit fly Drosophila melanogaster. The purpose of this project was to quantify the expression levels of Gst Delta class genes altered by aniline exposure and to understand the relationship between aniline dosages and the variation of Gst Delta genes expressed in D. melanogaster. Using RT-PCR expression assays, the expression patterns of the transcript mRNAs of the glutathione S-transferase Delta genes were revealed and their expression levels were measured at eggs, larvae, pupae and adults. The adult stage was selected for further dose-response assays. After analysis, the results indicated that three Gst Delta genes (Gst D2, Gst D5 and Gst D6) were found to show a peak of up-regulated transcriptional response at 6-8h of exposure of aniline. Furthermore, the dose-response relationship of their induction levels within the dose regiments (from 1.2 to 2.0 μl/tube) had been measured. The expression patterns and annotations of these genes were discussed in the context. PMID:25682008

  11. Exposure of Human Prostaspheres to Bisphenol A Epigenetically Regulates SNORD Family Noncoding RNAs via Histone Modification.

    PubMed

    Ho, Shuk-Mei; Cheong, Ana; Lam, Hung-Ming; Hu, Wen-Yang; Shi, Guang-Bin; Zhu, Xuegong; Chen, Jing; Zhang, Xiang; Medvedovic, Mario; Leung, Yuet-Kin; Prins, Gail S

    2015-11-01

    Bisphenol A (BPA) is a ubiquitous endocrine disruptor exerting lifelong effects on gene expression in rodent prostate cancer (PCa) models. Here, we aimed to determine whether epigenetic events mediating the action of BPA on human prostaspheres enriched in epithelial stem-like/progenitor cells is linked to PCa. We performed genome-wide transcriptome and methylome analyses to identify changes in prostaspheres treated with BPA (10 nM, 200 nM, and 1000 nM) or estradiol-17β (E2) (0.1 nM) for 7 days and validated changes in expression, methylation, and histone marks in parallel-treated prostaspheres. BPA/E2-treatment altered expression of 91 genes but not the methylation status of 485,000 CpG sites in BPA/E2-treated prostaspheres. A panel of 26 genes was found repressed in all treatment groups. Fifteen of them were small nucleolar RNAs with C/D motif (SNORDs), which are noncoding, small nucleolar RNAs known to regulate ribosomal RNA assembly and function. Ten of the most down-regulated SNORDs were further studied. All 10 were confirmed repressed by BPA, but only 3 ratified as E2-repressed. SNORD suppression showed no correlation with methylation status changes in CpG sites in gene regulatory regions. Instead, BPA-induced gene silencing was found to associate with altered recruitments of H3K9me3, H3K4me3, and H3K27me3 to 5'-regulatory/exonic sequences of 5 SNORDs. Expression of 4 out of these 5 SNORDs (SNORD59A, SNORD82, SNORD116, and SNORD117) was shown to be reduced in PCa compared with adjacent normal tissue. This study reveals a novel and unique action of BPA in disrupting expression of PCa-associated SNORDs and a putative mechanism for reprogramming the prostasphere epigenome via histone modification. PMID:26248216

  12. miR-214/199a/199a* cluster levels predict poor survival in hepatocellular carcinoma through interference with cell-cycle regulators

    PubMed Central

    Wu, Xiaojuan; Chen, Dabiao; Peng, Liang; Gao, Zhiliang; Xie, Chan

    2016-01-01

    Aims To identify the clinical and functional association of miR-214/199a/199a* cluster in human hepatocellular carcinoma (HCC) and to clarify the mechanism of miR-214. Methods Kaplan-Meier and Cox proportional regression analyses were used to determine the association of miR-214/199a/199a* cluster levels with the survival of HCC patients. The role of miR-214 in regulating HCC cell proliferation was studied with miR-214 mimics/inhibitor-treated cells. Furthermore, the inhibition effect of miR-214 on E2F2, cyclin-dependent kinase (CDK) 3 and CDK6 expression was assessed in HCC cell lines with miR-214 mimics/inhibitors to increase/decrease miR-214 expression. Direct binding of miR-214 to the 3′-untranslated regions of E2F2, CDK3, and CDK6 was verified by dual-luciferase reporter assay. Results In analyzing HCC clinical specimens and cell lines, we discovered a uniform decrease in miR-214/199a/199a* expression in comparison with noncancerous tissue or normal liver epithelial cell lines. Higher miR-214 levels were related with improved patient survival. Overexpression of miR-214 in HCC cells inhibited proliferation by inducing G1-S checkpoint arrest. Conversely, RNA interference–mediated silencing of miR-214 promoted cell-cycle progression and accelerated the proliferation of HCC cells. E2F2, CDK3 and CDK6 were each directly targeted for inhibition by miR-214, and restoring their expression reversed miR-214 inhibition of cell-cycle progression. The relationship between expression of miR-214 and its targets was confirmed in HCC tumor xenografts and clinical specimens. Conclusions Our results demonstrate that miR-214 has tumor-suppressive activity in HCC through inhibition of E2F2, CDK3 and CDK6. PMID:26498144

  13. Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels

    PubMed Central

    Corcoran, Jenna; Winter, Matthew J.; Lange, Anke; Cumming, Rob; Owen, Stewart F.; Tyler, Charles R.

    2015-01-01

    In mammals, the peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating various genes involved in lipid metabolism, bile acid synthesis and cholesterol homeostasis, and is activated by a diverse group of compounds collectively termed peroxisome proliferators (PPs). Specific PPs have been detected in the aquatic environment; however little is known on their pharmacological activity in fish. We investigated the bioavailability and persistence of the human PPARα ligand clofibric acid (CFA) in carp, together with various relevant endpoints, at a concentration similar to therapeutic levels in humans (20 mg/L) and for an environmentally relevant concentration (4 μg/L). Exposure to pharmacologically-relevant concentrations of CFA resulted in increased transcript levels of a number of known PPARα target genes together with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid metabolism pathways in carp which are known to be similarly activated in mammals. Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels of several biotransformation genes were also increased, paralleling previous reports in mammals and indicating a potential role in hepatic detoxification for PPARα in carp. Importantly, transcription of some of these genes (and Acox1 activity) were affected at exposure concentrations comparable with those reported in effluent discharges. Collectively, these data suggest that CFA is pharmacologically active in carp and has the potential to invoke PPARα-related responses in fish exposed in the environment, particularly considering that CFA may represent just one of a number of PPAR-active compounds present to which wild fish may be exposed. PMID:25749508

  14. Up-regulation of Gadd45α after Exposure to Metal Nanoparticles: the Role of Hypoxia Inducible Factor 1α

    PubMed Central

    Feng, Lingfang; Zhang, Yue; Jiang, Mizu; Mo, Yiqun; Wan, Rong; Jia, Zhenyu; Tollerud, David J.; Zhang, Xing; Zhang, Qunwei

    2014-01-01

    The increased development and use of nanoparticles in various fields may lead to increased exposure, directly affecting human health. Our current knowledge of the health effects of metal nanoparticles such as Cobalt and Titanium dioxide (Nano-Co and Nano-TiO2) is limited but suggests that some metal nanoparticles may cause genotoxic effects including cell cycle arrest, DNA damage and apoptosis. The growth arrest and DNA damage-inducible 45α protein (Gadd45α) has been characterized as one of the key players in the cellular responses to a variety of DNA damaging agents. The aim of this study was to investigate the alteration of Gadd45α expression in mouse embryo fibroblasts (PW) exposed to metal nanoparticles and the possible mechanisms. Non-toxic doses of Nano-Co and Nano-TiO2 were selected to treat cells. Our results showed that Nano-Co caused a dose- and time-dependent increase in Gadd45α expression, but Nano-TiO2 did not. To investigate the potential pathways involved in Nano-Co-induced Gadd45α up-regulation, we measured the expression of hypoxia inducible factor 1α (HIF-1α) in PW cells exposed to Nano-Co and Nano-TiO2. Our results showed that exposure to Nano-Co caused HIF-1α accumulation in the nucleus. In addition, hypoxia inducible factor 1α knock-out cells [HIF-1α (−/−)] and its wild-type cells [HIF-1α (+/+)] were used. Our results demonstrated that Nano-Co caused a dose- and time-dependent increase in Gadd45α expression in wild-type HIF-1α (+/+) cells, but only a slight increase in HIF-1α (−/−) cells. Pre-treatment of PW cells with heat shock protein 90 (Hsp90) inhibitor, 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG), prior to exposure to Nano-Co significantly abolished the Nano-Co-induced Gadd45α expression. These results suggest that HIF-1α accumulation may be partially involved in the increased Gadd45α expression in cells exposed to Nano-Co. These findings may have important implications for understanding the potential health

  15. An examination of the roles of trauma exposure and posttraumatic stress disorder on emotion regulation strategies of Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn veterans.

    PubMed

    Sippel, Lauren M; Roy, Alicia M; Southwick, Steven M; Fichtenholtz, Harlan M

    2016-09-01

    Theories of posttraumatic stress disorder (PTSD) implicate emotional processes, including difficulties utilizing adaptive emotion regulation strategies, as critical to the etiology and maintenance of PTSD. Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn (OIF/OEF/OND) veterans report high levels of combat exposure and PTSD. We aimed to extend findings suggesting that emotion regulation difficulties are a function of PTSD, rather than combat trauma exposure or common comorbidities, to OIF/OEF/OND veterans, in order to inform models of PTSD risk and recovery that can be applied to returning veterans. We tested differences in emotion regulation, measured with the Difficulties in Emotion Regulation Scale and Emotion Regulation Questionnaire, among trauma-exposed veterans with (n = 24) or without PTSD (n = 22) and healthy civilian comparison participants (n = 27) using multivariate analyses of covariance, adjusting for major depressive disorder, anxiety disorders, and demographic variables (age, sex, and ethnicity). Veterans with PTSD reported more use of expressive suppression and more difficulties with emotion regulation than veterans without PTSD and healthy comparison participants. Groups did not differ on cognitive reappraisal. Findings suggest the key role of PTSD above and beyond trauma exposure, depression, and anxiety in specific aspects of emotion dysregulation among OIF/OEF/OND veterans. Interventions that help veterans expand and diversify their emotion regulation skills may serve as helpful adjunctive treatments for PTSD among OIF/OEF/OND veterans. PMID:27195939

  16. Rich Donors, Poor Countries

    ERIC Educational Resources Information Center

    Thomas, M. A.

    2012-01-01

    The shifting ideological winds of foreign aid donors have driven their policy towards governments in poor countries. Donors supported state-led development policies in poor countries from the 1940s to the 1970s; market and private-sector driven reforms during the 1980s and 1990s; and returned their attention to the state with an emphasis on…

  17. Inference in `poor` languages

    SciTech Connect

    Petrov, S.

    1996-10-01

    Languages with a solvable implication problem but without complete and consistent systems of inference rules (`poor` languages) are considered. The problem of existence of finite complete and consistent inference rule system for a ``poor`` language is stated independently of the language or rules syntax. Several properties of the problem arc proved. An application of results to the language of join dependencies is given.

  18. Sexually dimorphic gene regulation in brain as a target for endocrine disrupters: developmental exposure of rats to 4-methylbenzylidene camphor.

    PubMed

    Maerkel, Kirsten; Durrer, Stefan; Henseler, Manuel; Schlumpf, Margret; Lichtensteiger, Walter

    2007-01-15

    The developing neuroendocrine brain represents a potential target for endocrine active chemicals. The UV filter 4-methylbenzylidene camphor (4-MBC) exhibits estrogenic activity, but also interferes with the thyroid axis. We investigated effects of pre- and postnatal exposure to 4-MBC in the same rat offspring at brain and reproductive organ levels. 4-MBC (7, 24, 47 mg/kg/day) was administered in chow to the parent generation before mating, during gestation and lactation, and to the offspring until adulthood. mRNA of estrogen target genes involved in control of sexual behavior and gonadal functions was measured by real-time RT-PCR in ventromedial hypothalamic nucleus (VMH) and medial preoptic area (MPO) of adult offspring. 4-MBC exposure affected mRNA levels of ER alpha, progesterone receptor (PR), preproenkephalin (PPE) and insulin-like growth factor-I (IGF-I) in a sex- and region-specific manner. In order to assess possible changes in sensitivity of target genes to estrogens, offspring were gonadectomized on day 70, injected with estradiol (E2, 10 or 50 microg/kg s.c.) or vehicle on day 84, and sacrificed 6 h later. The acute induction of PR mRNA, and repression (at 6 h) of PPE mRNA by E2 was enhanced by 4-MBC in male and female VMH and female MPO, whereas male MPO exhibited reduced responsiveness of both genes. Steroid receptor coactivator SRC-1 mRNA levels were increased in female VMH and MPO. The data indicate profound sex- and region-specific alterations in the regulation of estrogen target genes at brain level. Effect patterns in baseline and E2-induced gene expression differ from those in uterus and prostate. PMID:17188730

  19. Sexually dimorphic gene regulation in brain as a target for endocrine disrupters: Developmental exposure of rats to 4-methylbenzylidene camphor

    SciTech Connect

    Maerkel, Kirsten; Durrer, Stefan; Henseler, Manuel; Schlumpf, Margret; Lichtensteiger, Walter . E-mail: Walter.Lichtensteiger@access.unizh.ch

    2007-01-15

    The developing neuroendocrine brain represents a potential target for endocrine active chemicals. The UV filter 4-methylbenzylidene camphor (4-MBC) exhibits estrogenic activity, but also interferes with the thyroid axis. We investigated effects of pre- and postnatal exposure to 4-MBC in the same rat offspring at brain and reproductive organ levels. 4-MBC (7, 24, 47 mg/kg/day) was administered in chow to the parent generation before mating, during gestation and lactation, and to the offspring until adulthood. mRNA of estrogen target genes involved in control of sexual behavior and gonadal functions was measured by real-time RT-PCR in ventromedial hypothalamic nucleus (VMH) and medial preoptic area (MPO) of adult offspring. 4-MBC exposure affected mRNA levels of ER alpha, progesterone receptor (PR), preproenkephalin (PPE) and insulin-like growth factor-I (IGF-I) in a sex- and region-specific manner. In order to assess possible changes in sensitivity of target genes to estrogens, offspring were gonadectomized on day 70, injected with estradiol (E2, 10 or 50 {mu}g/kg s.c.) or vehicle on day 84, and sacrificed 6 h later. The acute induction of PR mRNA, and repression (at 6 h) of PPE mRNA by E2 was enhanced by 4-MBC in male and female VMH and female MPO, whereas male MPO exhibited reduced responsiveness of both genes. Steroid receptor coactivator SRC-1 mRNA levels were increased in female VMH and MPO. The data indicate profound sex- and region-specific alterations in the regulation of estrogen target genes at brain level. Effect patterns in baseline and E2-induced gene expression differ from those in uterus and prostate.

  20. VITELLOGENIN MRNA REGULATION AND PLASMA CLEARANCE IN MALE SHEEPSHEAD MINNOWS, CYPRINODON VARIEGATUS AFTER CESSATION OF EXPOSURE TO 17B-ESTRADIOL AND P-NONYLPHENOL

    EPA Science Inventory

    Research was conducted to determine the kinetics of hepatic vitellogenin (VTG) mRNA regulation and plasma VTG accumulation and clearance in male sheepshead minnows (Cyprinodon variegatus) during and after cessation of exposure to either 17b-estradiol (E2) or para-nonylphenol (NP)...

  1. Early soy exposure via maternal diet regulates rat mammary epithelial differentiation by paracrine signaling from stromal adipocytes.

    PubMed

    Su, Ying; Shankar, Kartik; Simmen, Rosalia C M

    2009-05-01

    Diet-mediated changes in transcriptional programs that promote the early differentiation of the mammary gland may lead to reduced breast cancer risk. The disparity in adult breast cancer incidence between Asian women and Western counterparts is attributed partly to high soy food intake. Here, we conducted genome-wide profiling of mammary tissues of weanling rats exposed to soy protein isolate (SPI) or control casein (CAS) via maternal diet to evaluate the contribution of early exposure on mammary gene expression. Of the identified 18 up- and 39 downregulated genes with SPI relative to CAS, a subset was associated with lipid metabolic pathways, consistent with reduced mammary adipocyte size and suggesting stromal adipocyte-specific genomic changes. Female offspring of rats fed SPI tended to have fewer terminal end buds (P = 0.06) and had significantly lower body weight and abdominal fat mass. To demonstrate the functional consequence of SPI-mediated adipocyte metabolic changes on neighboring mammary epithelium, the expression of in vivo regulated genes in 3T3-L1 adipocytes treated with soy isoflavone genistein and effects of the resultant conditioned medium (CM) on the differentiation of HC11 mammary epithelial cells were evaluated by quantitative RT-PCR and/or Western immunoblots. In differentiated 3T3-L1, genistein decreased fatty acid synthase and stearoyl-CoA desaturase and increased hydroxysteroid 11-beta dehydrogenase 1 expression. CM from genistein-treated adipocytes had higher adiponectin levels and augmented prolactin-induced, glucocorticoid-regulated beta-casein levels. These findings suggest that soy-associated components, by targeting mammary adipocytes, alter paracrine signaling to enhance mammary epithelial differentiation, with important implications for the prevention of breast cancer associated with obesity and obesity-related diseases. PMID:19321580

  2. Poorly controlled gout: who is doing poorly?

    PubMed Central

    Chia, Faith Li-Ann

    2016-01-01

    Gout, an inflammatory arthritis caused by the deposition of monosodium urate crystals, is commonly seen in primary care and specialist clinics. In recent years, there has been a resurgence of interest in gout due to advances in therapies and the understanding of pathophysiology, with new guidelines being published by international bodies. However, there is still a gap between the goals of treatment and actual day-to-day practice. Barriers that result in poorly controlled gout include patient factors such as lack of understanding of the disease, stigma and nonadherence to treatment, as well as physician factors such as knowledge gaps, inadequate use of allopurinol and lack of ownership of the disease. The medical profession needs to do more to bridge the gap through physician and patient education, identification of treatment targets with appropriate use of drugs, and dissemination of guidelines. PMID:27549096

  3. Poorly controlled gout: who is doing poorly?

    PubMed

    Chia, Faith Li-Ann

    2016-08-01

    Gout, an inflammatory arthritis caused by the deposition of monosodium urate crystals, is commonly seen in primary care and specialist clinics. In recent years, there has been a resurgence of interest in gout due to advances in therapies and the understanding of pathophysiology, with new guidelines being published by international bodies. However, there is still a gap between the goals of treatment and actual day-to-day practice. Barriers that result in poorly controlled gout include patient factors such as lack of understanding of the disease, stigma and nonadherence to treatment, as well as physician factors such as knowledge gaps, inadequate use of allopurinol and lack of ownership of the disease. The medical profession needs to do more to bridge the gap through physician and patient education, identification of treatment targets with appropriate use of drugs, and dissemination of guidelines. PMID:27549096

  4. High expression of piwi-like RNA-mediated gene silencing 1 is associated with poor prognosis via regulating transforming growth factor-β receptors and cyclin-dependent kinases in breast cancer.

    PubMed

    Cao, Jiwei; Xu, Gang; Lan, Jing; Huang, Qingqing; Tang, Zuxiong; Tian, Liping

    2016-03-01

    Previous studies have demonstrated that abnormal expression levels of PIWI may serve a crucial role in tumorigenesis. However, the pathological role and its association with prognosis remains to be fully elucidated. In the present study, the expression levels of piwi‑like RNA‑mediated gene silencing 1 (HIWI) and piwi‑like RNA‑mediated gene silencing 2 (HILI) in breast cancer tissues were reported to be high. The high expression levels of HIWI are correlated with poor prognosis in detected patients. In addition, by overexpression and interference, it was demonstrated that HIWI promotes the activity of breast cancer cells while depression of HIWI may induce apoptosis of breast cancer cells. It was additionally identified that suppression of HIWI may arrest the cells at the G2/M stage. The expression levels of transforming growth factor‑β receptor (TβR)I, TβRII, cyclin‑dependent kinase (CDK)4, CDK6 and CDK8 were observed to be regulated by HIWI, which indicated a novel mechanism of HIWI in the regulation of breast cancer progression. The present study provides novel insight into the HIWI expression in breast cancer, providing a potential biomarker for assessment of prognosis and therapy of breast cancer. PMID:26847393

  5. Maize miRNA and target regulation in response to hormone depletion and light exposure during somatic embryogenesis

    PubMed Central

    Chávez-Hernández, Elva C.; Alejandri-Ramírez, Naholi D.; Juárez-González, Vasti T.; Dinkova, Tzvetanka D.

    2015-01-01

    Maize somatic embryogenesis (SE) is induced from the immature zygotic embryo in darkness and under the appropriate hormones' levels. Small RNA expression is reprogrammed and certain miRNAs become particularly enriched during induction while others, characteristic to the zygotic embryo, decrease. To explore the impact of different environmental cues on miRNA regulation in maize SE, we tested specific miRNA abundance and their target gene expression in response to photoperiod and hormone depletion for two different maize cultivars (VS-535 and H-565). The expression levels of miR156, miR159, miR164, miR168, miR397, miR398, miR408, miR528, and some predicted targets (SBP23, GA-MYB, CUC2, AGO1c, LAC2, SOD9, GR1, SOD1A, PLC) were examined upon staged hormone depletion in the presence of light photoperiod or darkness. Almost all examined miRNA, except miR159, increased upon hormone depletion, regardless photoperiod absence/presence. miR528, miR408, and miR398 changed the most. On the other hand, expression of miRNA target genes was strongly regulated by the photoperiod exposure. Stress-related miRNA targets showed greater differences between cultivars than development-related targets. miRNA/target inverse relationship was more frequently observed in darkness than light. Interestingly, miR528, but not miR159, miR168 or miR398, was located on polyribosome fractions suggesting a role for this miRNA at the level of translation. Overall our results demonstrate that hormone depletion exerts a great influence on specific miRNA expression during plant regeneration independently of light. However, their targets are additionally influenced by the presence of photoperiod. The reproducibility or differences observed for particular miRNA-target regulation between two different highly embryogenic genotypes provide clues for conserved miRNA roles within the SE process. PMID:26257760

  6. Epigenetic regulation of spinal cord gene expression contributes to enhanced postoperative pain and analgesic tolerance subsequent to continuous opioid exposure

    PubMed Central

    Liang, De-Yong; Shi, Xiao-You; Sun, Yuan; Clark, J David

    2016-01-01

    involving Bdnf and Pdyn may contribute to the enhanced postoperative nociceptive sensitization and analgesic tolerance observed after continuous opioid exposure. Treatments blocking the epigenetically mediated up-regulation of these genes or administration of TrkB or κ-opioid receptor antagonists may improve the clinical utility of opioids, particularly after surgery. PMID:27094549

  7. Poor school performance.

    PubMed

    Karande, Sunil; Kulkarni, Madhuri

    2005-11-01

    Education is one of the most important aspects of human resource development. Poor school performance not only results in the child having a low self-esteem, but also causes significant stress to the parents. There are many reasons for children to under perform at school, such as, medical problems, below average intelligence, specific learning disability, attention deficit hyperactivity disorder, emotional problems, poor socio-cultural home environment, psychiatric disorders and even environmental causes. The information provided by the parents, classroom teacher and school counselor about the child's academic difficulties guides the pediatrician to form an initial diagnosis. However, a multidisciplinary evaluation by an ophthalmologist, otolaryngologist, counselor, clinical psychologist, special educator, and child psychiatrist is usually necessary before making the final diagnosis. It is important to find the reason(s) for a child's poor school performance and come up with a treatment plan early so that the child can perform up to full potential. PMID:16391452

  8. National radiation exposures and risks caused by implementing EPA`s proposed revised national primary drinking water regulations

    SciTech Connect

    Morris, S.C.; Rowe, M.D.; Holtzman, S.; Meinhold, A.F.

    1993-05-01

    This report estimates risks to workers and the public associated with treatment processes and their associated waste products that would be mandated under proposed regulations of radium, radon, and uranium in drinking water. Three scenarios were examined: (1) all wastes flushed to the sanitary sewer; (2) all wastes disposed on land; (3) similar to (2) but radon removal by granulated activated carbon rather than packed tower aeration. Risks considered included accidental injury and cancer. Worker risks for both scenarios I and II were estimated to be 0.025 and 0.01 deaths per year of operation for radium-226 and radium-228, respectively. Worker risks for uranium were estimated to be 0.13 deaths/year of operation for scenario I and 0.5 deaths/year of operation for scenario II. Worker risks for radon removal were estimated to be 1.7 deaths/year of operation for scenario I and 2.2 deaths/year of operation for scenario II. Risks to the public for scenarios I and II for radium-226 were 4 {times} 10{sup {minus}4} and for radium-228 were 9 {times} 10{sup {minus}5} deaths/year of operation. Risks to the public for scenarios I and II for uranium were 7.3 {times} 10{sup {minus}2} and 2 {times} 10{sup {minus}4}, respectively. Risks to the public for scenario I and II for radon were 24 deaths/year of operation and for scenario III were nil. Public risks were quantified only for people exposed during a year of operation. For example, effects of public exposures in future years via groundwater contamination associated with landfill of treatment waste were not considered.

  9. Morphosyntax in Poor Comprehenders

    ERIC Educational Resources Information Center

    Adlof, Suzanne M.; Catts, Hugh W.

    2015-01-01

    Children described as "poor comprehenders" (PCs) have reading comprehension difficulties in spite of adequate word reading abilities. PCs are known to display weakness with semantics and higher-level aspects of oral language, but less is known about their grammatical skills, especially with regard to morphosyntax. The purpose of this…

  10. Vitellogenin mRNA regulation and plasma clearance in male sheepshead minnows, (Cyprinodon variegatus) after cessation of exposure to 17 beta-estradiol and p-nonylphenol.

    PubMed

    Hemmer, Michael J; Bowman, Christopher J; Hemmer, Becky L; Friedman, Stephanie D; Marcovich, Dragoslav; Kroll, Kevin J; Denslow, Nancy D

    2002-07-01

    Research was conducted to determine the kinetics of hepatic vitellogenin (VTG) mRNA regulation and plasma VTG accumulation and clearance in male sheepshead minnows (Cyprinodon variegatus) during and after cessation of exposure to either 17 beta-estradiol (E2) or para-nonylphenol (NP). Adult fish were continuously exposed to aqueous measured concentrations of 0.089 and 0.71 microg E2 per l, and 5.6 and 59.6 microg NP per l for 16 days using an intermittent flow-through dosing apparatus. Fish were sampled on days 8 and 16 of exposure followed by sampling at discrete intervals for up to 96 days post-exposure. At each interval five fish were randomly sampled from each concentration and hepatic VTG mRNA and serum VTG levels for individual fish determined by slot blot and direct enzyme-linked immunosorbent assay (ELISA), respectively. Exposure to E2 and NP resulted in a dose dependent increase in hepatic VTG mRNA and plasma VTG over the course of the 16-day exposure period. Mean plasma VTG levels at day 16 were >100 mg/ml for both high doses of E2 and NP, and >20 mg/ml for the low exposure treatments. Within 8 days post-exposure, hepatic VTG mRNA levels returned to baseline in both high and low E2 treatments but remained elevated 2-4 fold in the NP treatments. Due to a shortened sampling period, a clearance rate for plasma VTG in the 5.6 microg NP per l treatment could not determined. In the 0.089, 0.71 microg E2 per l, and 59.6 microg NP per l treatments, VTG levels began decreasing within 4 days after exposure cessation and exhibited an exponential rate of elimination from plasma. Clearance rates for 0.71 microg E2 per l and 59.6 microg NP per l were not significantly different (P=0.47), however, both demonstrated significantly higher rates of clearance (P<0.02) than observed in the 0.089 microg E2 per l treatment. Our results indicate that hepatic VTG mRNA rapidly diminishes after cessation of estrogenic exposure in sheepshead minnows, but plasma VTG clearance is

  11. Regulation of COX-2 expression and epithelial-to-mesenchymal transition by hypoxia-inducible factor-1α is associated with poor prognosis in hepatocellular carcinoma patients post TACE surgery

    PubMed Central

    HUANG, MINGSHENG; WANG, LONG; CHEN, JUNWEI; BAI, MINGJUN; ZHOU, CHUREN; LIU, SUJUAN; LIN, QU

    2016-01-01

    Currently, it is not entirely clear whether hypoxia-inducible factor-1α (HIF-1α) is involved in the regulation of COX-2 expression and epithelial-to-mesenchymal transition (EMT), and whether these events affect the prognosis of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE). In this report the relationship between HIF-1α and COX-2 protein expression, EMT in tumor specimens from HCC patients after TACE surgery and the clinical significance of HIF-1α and COX-2 expression were analyzed using statistical approaches. HepG2 cells treated with CoCl2 was employed as a hypoxia cell model in vitro to study hypoxia-induced HIF-1α, COX-2 expression, and EMT alteration. The results showed that HIF-1α and COX-2 protein expression increased in HCC tissues after TACE surgery. Moreover, there was positive correlation between upregulation of HIF-1α and COX-2. Elevated expression of HIF-1α increased both Snail and Vimentin protein expression, while it reduced E-cadherin protein expression. It was further verified that hypoxia enhanced protein expression of HIF-1α and COX-2 in HepG2 cells treated with CoCl2. Upregulation of HIF-1α and COX-2, together with EMT alteration resulted in increased migration and invasion of HepG2 cells under hypoxia. In conclusion, TACE surgery results in aggravated hypoxia status, leading to increased HIF-1α protein expression in HCC tissue. To adapt to hypoxic environment, HIF-1α stimulates COX-2 protein expression and promotes EMT process in hepatocellular cancer cells, which enhances HCC invasion and metastasis, and might contribute to poor prognosis in HCC patients post TACE treatment. PMID:26984380

  12. Analysis of cell cycle regulated and regulating proteins following exposure of lung derived cells to sub-lethal doses of a-rays

    NASA Astrophysics Data System (ADS)

    Trani, D.; Claudio, P. P.; Cassone, M.; Lucchetti, C.; D'Agostino, L.; Caputi, M.; Giordano, A.

    Introduction Since the last century mankind had to face an increased exposure to man made and natural sources of radiation Radiation represents a therapeutic instrument for radiosensitive cancers as well as a cytotoxic agent for normal human tissues The effects of prolonged exposure to low doses of high energy radiation are still not well-known at the molecular and clinical level Understanding their molecular effects will aid in developing more tailored therapeutic strategies as well as implementing radio-protective measures essential prerequisite for the long-time permanence of men in space Objective of the study The general aim of this study was to evaluate the susceptibility and the response of lung epithelial cells to DNA damage induced by ionizing radiations We decided to study a panel of epithelial bronchial cell lines because of their fast-growth rate and their prominent exposure to both environmental and medical radiations The specific objective of our study was to qualitatively and semi-quantitatively assess the involvement and behaviour of selected genes in DNA damage DNA-repair mechanisms and apoptosis which follow radiation exposure with the aim to determine the involvement of the most promising targets for the early detection of radiation-mediated lung damage before chronic disease develops Methods Four epithelial cell lines one normal and three neoplastic were selected in order to detect and compare survival cell cycle and protein expression differences related to their different genetic asset

  13. The systematic regulation of oyster CgIL17-1 and CgIL17-5 in response to air exposure.

    PubMed

    Xin, Lusheng; Zhang, Huan; Du, Xinyu; Li, Yiqun; Li, Meijia; Wang, Lingling; Wang, Hao; Qiu, Limei; Song, Linsheng

    2016-10-01

    As a proinflammatory cytokine, vertebrate interleukin 17 (IL17) plays a vital role in the balance of inflammation and homeostasis, and is involved in a systemic regulation of glucose homeostasis. In the present study, a remarkable increase of glucose concentration was observed in oyster serum after 2 d air exposure, which was followed by a rapid up-regulation of CgIL17-1 and CgIL17-5. After oysters was received an injection of extra glucose, the mRNA expressions of CgIL17-1 and CgIL17-5 were also significantly up-regulated. The histopathological changes of hepatopancreas were observed after the oysters were treated by the recombinant proteins of CgIL17-1 and CgIL17-5 in vivo or subjected to air exposure. A significant decrease of GSK3β (Glycogen synthase kinase-3β) protein was also observed after the injection of CgIL17-1 and CgIL17-5 recombinant proteins in vivo. When the oysters with CgIL17-1 and CgIL17-5 genes knocked down were subjected to air exposure, the decline of GSK3β concentration was slowed down and it could still be obviously detected after 7 d compared with that in the control. Meanwhile, the expression of CgDefensin and CgDFFA was inhibited, while CgIAP was up-regulated when CgIL17-1 and CgIL17-5 genes were knocked down, and the oysters exhibited higher mortality (p < 0.05) at 3 d, whereas lower at the late stage of air exposure compared with that in the controls. The results collectively suggested that once oysters were exposed to air, the synthesis of proinflammatory cytokines CgIL17-1 and CgIL17-5 was induced by the up-regulated glucose concentration in oyster serum, which would be not only a negative feedback to the high glucose concentration through mediating the regulation of GSK3β, but also an inducer on tissue damage and immunocompetence as well as the adaptability to stresses. PMID:27268575

  14. Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor

    PubMed Central

    St-Cyr, Sophie; McGowan, Patrick O.

    2015-01-01

    Perinatal stress mediated through the mother can lead to long-term alterations in stress-related phenotypes in offspring. The capacity for adaptation to adversity in early life depends in part on the life history of the animal. This study was designed to examine the behavioral and neural response in adult offspring to prenatal exposure to predator odor: an ethologically-relevant psychological stressor. Pregnant mice were exposed daily to predator odors or distilled water control over the second half of the pregnancy. Predator odor exposure lead to a transient decrease in maternal care in the mothers. As adults, the offspring of predator odor-exposed mothers showed increased anti-predator behavior, a predator-odor induced decrease in activity and, in female offspring, an increased corticosterone (CORT) response to predator odor exposure. We found a highly specific response among stress-related genes within limbic brain regions. Transcript abundance of Corticotropin-releasing hormone receptor 1 (CRHR1) was elevated in the amygdala in adult female offspring of predator odor-exposed mothers. In the hippocampus of adult female offspring, decreased Brain-derived neurotrophic factor (BDNF) transcript abundance was correlated with a site-specific decrease in DNA methylation in Bdnf exon IV, indicating the potential contribution of this epigenetic mechanism to maternal programming by maternal predator odor exposure. These data indicate that maternal predator odor exposure alone is sufficient to induce an altered stress-related phenotype in adulthood, with implications for anti-predator behavior in offspring. PMID:26082698

  15. Effects of Hypoxia Exposure on Hepatic Cytochrome P450 1A (CYP1A) Expression in Atlantic Croaker: Molecular Mechanisms of CYP1A Down-Regulation

    PubMed Central

    Rahman, Md. Saydur; Thomas, Peter

    2012-01-01

    Hypoxia-inducible factor-α (HIF-α) and cytochrome P450 1A (CYP1A) are biomarkers of environmental exposure to hypoxia and organic xenobiotic chemicals that act through the aryl hydrocarbon receptor, respectively. Many aquatic environments heavily contaminated with organic chemicals, such as harbors, are also hypoxic. Recently, we and other scientists reported HIF-α genes are upregulated by hypoxia exposure in aquatic organisms, but the molecular mechanisms of hypoxia regulation of CYP1A expression have not been investigated in teleost fishes. As a first step in understanding the molecular mechanisms of hypoxia modulation of CYP1A expression in fish, we characterized CYP1A cDNA from croaker liver. Hypoxia exposure (dissolved oxygen, DO: 1.7 mg/L for 2 to 4 weeks) caused significant decreases in hepatic CYP1A mRNA and protein levels compared to CYP1A levels in fish held in normoxic conditions. In vivo studies showed that the nitric oxide (NO)-donor, S-nitroso-N-acetyl-DL-penicillamine, significantly decreased CYP1A expression in croaker livers, whereas the competitive inhibitor of NO synthase (NOS), Nω-nitro-L-arginine methyl ester, restored CYP1A mRNA and protein levels in hypoxia-exposed (1.7 mg DO/L for 4 weeks) fish. In vivo hypoxia exposure also markedly increased interleukin-1β (IL-1β, a cytokine), HIF-2α mRNA and endothelial NOS (eNOS) protein levels in croaker livers. Pharmacological treatment with vitamin E, an antioxidant, lowered the IL-1β, HIF-2α mRNA and eNOS protein levels in hypoxia-exposed fish and completely reversed the down-regulation of hepatic CYP1A mRNA and protein levels in response to hypoxia exposure. These results suggest that hypoxia-induced down-regulation of CYP1A is due to alterations of NO and oxidant status, and cellular IL-1β and HIF-α levels. Moreover, the present study provides the first evidence of a role for antioxidants in hepatic eNOS and IL-1β regulation in aquatic vertebrates during hypoxic stress. PMID:22815834

  16. Poor ovarian reserve.

    PubMed

    Jirge, Padma Rekha

    2016-01-01

    Poor ovarian reserve (POR) is an important limiting factor for the success of any treatment modality for infertility. It indicates a reduction in quantity and quality of oocytes in women of reproductive age group. It may be age related as seen in advanced years of reproductive life or may occur in young women due to diverse etiological factors. Evaluating ovarian reserve and individualizing the therapeutic strategies are very important for optimizing the success rate. Majority or women with POR need to undergo in vitro fertilization to achieve pregnancy. However, pregnancy rate remains low despite a plethora of interventions and is associated with high pregnancy loss. Early detection and active management are essential to minimize the need for egg donation in these women. PMID:27382229

  17. Poor ovarian reserve

    PubMed Central

    Jirge, Padma Rekha

    2016-01-01

    Poor ovarian reserve (POR) is an important limiting factor for the success of any treatment modality for infertility. It indicates a reduction in quantity and quality of oocytes in women of reproductive age group. It may be age related as seen in advanced years of reproductive life or may occur in young women due to diverse etiological factors. Evaluating ovarian reserve and individualizing the therapeutic strategies are very important for optimizing the success rate. Majority or women with POR need to undergo in vitro fertilization to achieve pregnancy. However, pregnancy rate remains low despite a plethora of interventions and is associated with high pregnancy loss. Early detection and active management are essential to minimize the need for egg donation in these women. PMID:27382229

  18. Inhibition of P-Glycoprotein and Multidrug Resistance-Associated Protein 2 Regulates the Hepatobiliary Excretion and Plasma Exposure of Thienorphine and Its Glucuronide Conjugate

    PubMed Central

    Kong, Ling-Lei; Shen, Guo-Lin; Wang, Zhi-Yuan; Zhuang, Xiao-Mei; Xiao, Wei-Bin; Yuan, Mei; Gong, Ze-Hui; Li, Hua

    2016-01-01

    Thienorphine (TNP) is a novel partial opioid agonist that has completed phase II clinical evaluation as a promising drug candidate for the treatment of opioid dependence. Previous studies have shown that TNP and its glucuronide conjugate (TNP-G) undergo significant bile excretion. The purpose of this study was to investigate the roles of efflux transporters in regulating biliary excretion and plasma exposure of TNP and TNP-G. An ATPase assay suggested that TNP and TNP-G were substrates of P-gp and MRP2, respectively. The in vitro data from rat hepatocytes showed that bile excretion of TNP and TNP-G was regulated by the P-gp and MRP2 modulators. The accumulation of TNP and TNP-G in HepG2 cells significantly increased by the treatment of mdr1a or MRP2 siRNA for P-gp or MRP2 modulation. In intact rats, the bile excretion, and pharmacokinetic profiles of TNP and TNP-G were remarkably changed with tariquidar and probenecid pretreatment, respectively. Tariquidar increased the Cmax and AUC0-t and decreased MRT and T1/2 of TNP, whereas probenecid decreased the plasma exposure of TNP-G and increased its T1/2. Knockdown P-gp and MRP2 function using siRNA significantly increased the plasma exposure of TNP and TNP-G and reduced their mean retention time in mice. These results indicated the important roles of P-gp and MRP2 in hepatobiliary excretion and plasma exposure of TNP and TNP-G. Inhibition of the efflux transporters may affect the pharmacokinetics of TNP and result in a drug-drug interaction between TNP and the concomitant transporter inhibitor or inducer in clinic. PMID:27555820

  19. [Current options to manage clopidogrel poor responsiveness].

    PubMed

    Fileti, Luca; Campo, Gianluca; Valgimigli, Marco; Marchesini, Jlenia; Ferrari, Roberto

    2010-12-01

    Antiplatelet therapy (aspirin + clopidogrel) is the cornerstone of treatment for patients with acute coronary syndromes and/or undergoing percutaneous coronary interventions (PCI). More than 40 million patients worldwide receive clopidogrel, but about 20% of them are nonresponders or poor responders. Many studies using different techniques, platelet agonists and definitions have shown that patients who are poor responders to clopidogrel have an increased risk of death, reinfarction and stent thrombosis. The mechanisms leading to poor responsiveness are not fully elucidated and are likely multifactorial: genetic factors, accelerated platelet turnover, up-regulation of the P2Y12 pathways, high baseline platelet reactivity, poor compliance, underdosing and drug-drug interactions. The management of these patients is very difficult, but evidence does exist showing that a strategy of higher maintenance dose or switch to different thienopyridines (e.g. ticlopidine or prasugrel) or use of glycoprotein IIb/IIIa inhibitors during PCI may be helpful to overcome poor responsiveness and improve the long-term clinical outcome. This review describes the impact of poor responsiveness to clopidogrel on clinical outcomes, the mechanisms leading to poor effect, and the different assays to assess it. Finally, current and future options for its management are discussed. PMID:21355335

  20. Cigarette smoke exposure reveals a novel role for the MEK/ERK1/2 MAPK pathway in regulation of CFTR

    PubMed Central

    Xu, Xiaohua; Balsiger, Robert; Tyrrell, Jean; Boyaka, Prosper N.; Tarran, Robert; Cormet-Boyaka, Estelle

    2015-01-01

    Background CFTR plays a key role in maintenance of lung fluid homeostasis. Cigarette smoke decreases CFTR expression in the lung but neither the mechanisms leading to CFTR loss, nor potential ways to prevent its loss have been identified to date. Methods The molecular mechanisms leading to down-regulation of CFTR by cigarette smoke were determined using pharmacologic inhibitors and silencing RNAs. Results Using human bronchial epithelial cells, here we show that cigarette smoke induces degradation of CFTR that is attenuated by the lysosomal inhibitors, but not proteasome inhibitors. Cigarette smoke can activate multiple signaling pathways in airway epithelial cells, including the MEK/Erk1/2 MAPK pathway regulating cell survival. Interestingly, pharmacological inhibition of the MEK/Erk1/2 MAPK pathway prevented the loss of plasma membrane CFTR upon cigarette smoke exposure. Similarly, decreased expression of Erk1/2 using silencing RNAs prevented the suppression of CFTR protein by cigarette smoke. Conversely, specific inhibitors of the JNK or p38 MAPK pathways had no effect on CFTR decrease after cigarette smoke exposure. In addition, inhibition of the MEK/Erk1/2 MAPK pathway prevented the reduction of the airway surface liquid observed upon cigarette smoke exposure of primary human airway epithelial cells. Finally, addition of the antioxidant NAC inhibited activation of Erk1/2 by cigarette smoke and precluded the cigarette smoke-induced decrease of CFTR. Conclusions These results show that the MEK/Erk1/2 MAPK pathway regulates plasma membrane CFTR in human airway cells. General Significance The MEK/Erk1/2 MAPK pathway should be considered as a target for strategies to maintain/restore CFTR expression in the lung of smokers. PMID:25697727

  1. Morphosyntax in Poor Comprehenders

    PubMed Central

    Adlof, Suzanne M.; Catts, Hugh W.

    2016-01-01

    Children described as poor comprehenders (PCs) have reading comprehension difficulties in spite of adequate word reading abilities. PCs are known to display weakness with semantics and higher-level aspects of oral language, but less is known about their grammatical skills, especially with regard to morphosyntax. The purpose of this study was to examine morphosyntax in fourth grade PCs and typically developing readers (TDs), using three experimental tasks involving finiteness marking. Participants also completed standardized, norm-referenced assessments of phonological memory, vocabulary, and broader language skills. PCs displayed weakness relative to TDs on all three morphosyntax tasks and on every other assessment of oral language except phonological memory, as indexed by nonword repetition. These findings help to clarify the linguistic profile of PCs, suggesting that their language weaknesses include grammatical weaknesses that cannot be fully explained by semantic factors. Because finiteness markers are usually mastered prior to formal schooling in typical development, we call for future studies to examine whether assessments of morphosyntax could be used for the early identification of children at risk for future reading comprehension difficulty.

  2. Epigenetic Regulation of Immunological Alterations Following Prenatal Exposure to Marijuana Cannabinoids and its Long Term Consequences in Offspring.

    PubMed

    Zumbrun, Elizabeth E; Sido, Jessica M; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2015-06-01

    Use of marijuana during pregnancy is fairly commonplace and can be expected increase in frequency as more states legalize its recreational use. The cannabinoids present in marijuana have been shown to be immunosuppressive, yet the effect of prenatal exposure to cannabinoids on the immune system of the developing fetus, its long term consequences during adult stage of life, and transgenerational effects have not been well characterized. Confounding factors such as co-existing drug use make the impact of cannabis use on progeny inherently difficult to study in a human population. Data from various animal models suggests that in utero exposure to cannabinoids results in profound T cell dysfunction and a greatly reduced immune response to viral antigens. Furthermore, evidence from animal studies indicates that the immunosuppressive effects of cannabinoids can be mediated through epigenetic mechanisms such as altered microRNA, DNA methylation and histone modification profiles. Such studies support the hypothesis that that parental or prenatal exposure to cannabis can trigger epigenetic changes that could have significant immunological consequences for offspring as well as long term transgenerational effects. PMID:25618446

  3. Alterations in the oxidative metabolism of Rhipicephalus (Boophilus) microplus ticks in response to exposure to the insect growth regulator fluazuron.

    PubMed

    Gaudêncio, Fabrício Nascimento; Tunholi-Alves, Vinícius Menezes; Lima, Mariana Gomes; Gôlo, Patrícia Silva; Angelo, Isabele da Costa; Castro, Rosane Nora; Fonseca, Adivaldo Henrique da; Scott, Fabio Barbour; Pinheiro, Jairo

    2016-01-01

    Aiming to characterize the potential off-target effects of fluazuron on ticks, biochemical analyses were conducted to evaluate changes in the carbohydrate metabolism of Rhipicephalus (Boophilus) microplus ticks after exposure to fluazuron. Hemolymph and fat body were collected from female ticks before and after (4, 8 and 15 days) exposure to fluazuron. Spectrophotometric analyses were done to quantify glucose concentration and lactate dehydrogenase (LDH) activity in the hemolymph and the concentration of glycogen in the tick's fat body. High Performance Liquid Chromatography (HPLC) was employed to determine the concentration of carboxylic acids in the hemolymph and to evaluate changes in intermediary metabolic processes requiring oxygen consumption. Increases in the levels of LDH activity and lactic acid concentration indicated that fluazuron enhanced fermentative metabolism in ticks. Exposure to fluazuron was also found to increase glucose concentrations in the hemolymph over time, although no significant differences were noted daily. In addition to expanding the body of knowledge about the mode of action of fluazuron, investigations into these mechanisms may also be useful in discovering new and as yet unexplored secondary effects. PMID:26982563

  4. Epigenetic Regulation of Immunological Alterations Following Prenatal Exposure to Marijuana Cannabinoids and its Long Term Consequences in Offspring

    PubMed Central

    Zumbrun, Elizabeth E.; Sido, Jessica M.; Nagarkatti, Prakash S.

    2015-01-01

    Use of marijuana during pregnancy is fairly commonplace and can be expected increase in frequency as more states legalize its recreational use. The cannabinoids present in marijuana have been shown to be immunosuppressive, yet the effect of prenatal exposure to cannabinoids on the immune system of the developing fetus, its long term consequences during adult stage of life, and transgenerational effects have not been well characterized. Confounding factors such as coexisting drug use make the impact of cannabis use on progeny inherently difficult to study in a human population. Data from various animal models suggests that in utero exposure to cannabinoids results in profound T cell dysfunction and a greatly reduced immune response to viral antigens. Furthermore, evidence from animal studies indicates that the immunosuppressive effects of cannabinoids can be mediated through epigenetic mechanisms such as altered microRNA, DNA methylation and histone modification profiles. Such studies support the hypothesis that that parental or prenatal exposure to cannabis can trigger epigenetic changes that could have significant immunological consequences for offspring as well as long term transgenerational effects. PMID:25618446

  5. Bacillus thermoamylovorans Spores with Very-High-Level Heat Resistance Germinate Poorly in Rich Medium despite the Presence of ger Clusters but Efficiently upon Exposure to Calcium-Dipicolinic Acid.

    PubMed

    Berendsen, Erwin M; Krawczyk, Antonina O; Klaus, Verena; de Jong, Anne; Boekhorst, Jos; Eijlander, Robyn T; Kuipers, Oscar P; Wells-Bennik, Marjon H J

    2015-11-01

    High-level heat resistance of spores of Bacillus thermoamylovorans poses challenges to the food industry, as industrial sterilization processes may not inactivate such spores, resulting in food spoilage upon germination and outgrowth. In this study, the germination and heat resistance properties of spores of four food-spoiling isolates were determined. Flow cytometry counts of spores were much higher than their counts on rich medium (maximum, 5%). Microscopic analysis revealed inefficient nutrient-induced germination of spores of all four isolates despite the presence of most known germination-related genes, including two operons encoding nutrient germinant receptors (GRs), in their genomes. In contrast, exposure to nonnutrient germinant calcium-dipicolinic acid (Ca-DPA) resulted in efficient (50 to 98%) spore germination. All four strains harbored cwlJ and gerQ genes, which are known to be essential for Ca-DPA-induced germination in Bacillus subtilis. When determining spore survival upon heating, low viable counts can be due to spore inactivation and an inability to germinate. To dissect these two phenomena, the recoveries of spores upon heat treatment were determined on plates with and without preexposure to Ca-DPA. The high-level heat resistance of spores as observed in this study (D120°C, 1.9 ± 0.2 and 1.3 ± 0.1 min; z value, 12.2 ± 1.8°C) is in line with survival of sterilization processes in the food industry. The recovery of B. thermoamylovorans spores can be improved via nonnutrient germination, thereby avoiding gross underestimation of their levels in food ingredients. PMID:26341201

  6. Bacillus thermoamylovorans Spores with Very-High-Level Heat Resistance Germinate Poorly in Rich Medium despite the Presence of ger Clusters but Efficiently upon Exposure to Calcium-Dipicolinic Acid

    PubMed Central

    Berendsen, Erwin M.; Krawczyk, Antonina O.; Klaus, Verena; de Jong, Anne; Boekhorst, Jos; Eijlander, Robyn T.

    2015-01-01

    High-level heat resistance of spores of Bacillus thermoamylovorans poses challenges to the food industry, as industrial sterilization processes may not inactivate such spores, resulting in food spoilage upon germination and outgrowth. In this study, the germination and heat resistance properties of spores of four food-spoiling isolates were determined. Flow cytometry counts of spores were much higher than their counts on rich medium (maximum, 5%). Microscopic analysis revealed inefficient nutrient-induced germination of spores of all four isolates despite the presence of most known germination-related genes, including two operons encoding nutrient germinant receptors (GRs), in their genomes. In contrast, exposure to nonnutrient germinant calcium-dipicolinic acid (Ca-DPA) resulted in efficient (50 to 98%) spore germination. All four strains harbored cwlJ and gerQ genes, which are known to be essential for Ca-DPA-induced germination in Bacillus subtilis. When determining spore survival upon heating, low viable counts can be due to spore inactivation and an inability to germinate. To dissect these two phenomena, the recoveries of spores upon heat treatment were determined on plates with and without preexposure to Ca-DPA. The high-level heat resistance of spores as observed in this study (D120°C, 1.9 ± 0.2 and 1.3 ± 0.1 min; z value, 12.2 ± 1.8°C) is in line with survival of sterilization processes in the food industry. The recovery of B. thermoamylovorans spores can be improved via nonnutrient germination, thereby avoiding gross underestimation of their levels in food ingredients. PMID:26341201

  7. Brief Report: Platelet-Poor Plasma Serotonin in Autism

    ERIC Educational Resources Information Center

    Anderson, George M.; Hertzig, Margaret E.; McBride, P. A.

    2012-01-01

    Possible explanations for the well-replicated platelet hyperserotonemia of autism include an alteration in the platelet's handling of serotonin (5-hydroxyserotonin, 5-HT) or an increased exposure of the platelet to 5-HT. Measurement of platelet-poor plasma (PPP) levels of 5-HT appears to provide the best available index of in vivo exposure of the…

  8. Epigenetic regulation of neurodevelopmental genes in response to in utero exposure to phthalate plastic chemicals: How can we delineate causal effects?

    PubMed

    Ponsonby, Anne-Louise; Symeonides, Christos; Vuillermin, Peter; Mueller, Jochen; Sly, Peter D; Saffery, Richard

    2016-07-01

    Accumulating evidence, from animal models and human observational studies, implicates the in utero (and early postnatal) environment in the 'programming' of risk for a variety of adverse outcomes and health trajectories. The modern environment is replete with man-made compounds such as plastic product chemicals (PPC), including phenols and phthalates. Evidence from several human cohorts implicates exposure to these chemicals in adverse offspring neurodevelopment, though a direct causal relationship has not been firmly established. In this review we consider a potential causal pathway that encompasses epigenetic human variation, and how we might test this mechanistic hypothesis in human studies. In the first part of this report we outline how PPCs induce epigenetic change, focusing on the brain derived neurotrophic factor (BDNF) gene, a key regulator of neurodevelopment. Further, we discuss the role of the epigenetics of BDNF and other genes in neurodevelopment and the emerging human evidence of an association between phthalate exposure and adverse offspring neurodevelopment. We discuss aspects of epidemiological and molecular study design and analysis that could be employed to strengthen the level of human evidence to infer causality. We undertake this using an exemplar recent research example: maternal prenatal smoking, linked to methylation change at the aryl hydrocarbon receptor repressor (AHRR) gene at birth, now shown to mediate some of the effects of maternal smoking on birth weight. Characterizing the relationship between the modern environment and the human molecular pathways underpinning its impact on early development is paramount to understanding the public health significance of modern day chemical exposures. PMID:27208563

  9. Regulation of GM-CSF and IL-3 production from the murine keratinocyte cell line PAM 212 following exposure to ultraviolet radiation

    SciTech Connect

    Gallo, R.L.; Staszewski, R.; Sauder, D.N.; Knisely, T.L.; Granstein, R.D. )

    1991-08-01

    Ultraviolet radiation (UVR) exposure induces profound changes in the synthesis and secretion of various cytokines both in vivo and in vitro. Little is known regarding the mechanism of these responses. This investigation evaluated the effects of UVR on the ability of a murine keratinocyte line (PAM 212) to produce interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF). Subconfluent rapidly dividing PAM 212 cells were shown by RNA slot-blot hybridization studies to have increased levels of mRNA for both IL-3 and GM-CSF within 1 h of UVR exposure. However, only GM-CSF-specific bioactivity, as determined by antibody neutralization studies, was shown to increase above baseline in cell supernatants. Cells grown to confluence responded differently to UVR. Under these culture conditions an apparent decrease in bioactivity was detected after UVR exposure for both growth factors, and no change in mRNA levels was detected. In addition to culture density, removal of extracellular calcium or sodium during irradiation, treatment with amiloride, or inhibition of new mRNA synthesis with cordycepin was shown to influence the UVR-induced alteration in release of IL-3 or GM-CSF bioactivity from both confluent and subconfluent PAM 212 cells. These results demonstrate that UVR influences the release of the colony stimulating factors GM-CSF and IL-3 from keratinocyte, and suggests that the state of cell growth and conditions of membrane ion transport influence the mechanisms regulating secretion of those factors.

  10. Differential regulation of sodium-potassium pump isoforms during smolt development and seawater exposure of Atlantic salmon

    USGS Publications Warehouse

    McCormick, Stephen D.; Regish, Amy M.; Christensen, Arne K.; Björnsson, Björn Thrandur

    2013-01-01

    Freshwater and seawater isoforms of the alpha subunit of Na+/K+-ATPase (NKA) have previously been identified in gill ionocytes of Atlantic salmon (Salmo salar). In the present study we examine the abundance and cellular localization of these isoforms during the parr–smolt transformation, a developmental process that is preparatory for seawater entry. The abundance of NKAα1a was lower in smolts than in parr, remained relatively constant during spring and decreased in summer. NKAα1b increased tenfold in smolts during spring, peaking in late April, coincident with downstream migration and increased salinity tolerance. NKAα1b increased a further twofold after seawater exposure of smolts, whereas NKAα1a decreased by 98%. The abundance of NKAα1b-positive, and NKAα1b and NKAα1a co-labeled ionocytes increased during smolt development, whereas the number of NKAα1a cells decreased. After seawater exposure of smolts, NKAα1b-positive ionocytes increased, NKAα1a-positive cells decreased, and co-labeled cells disappeared. Plasma growth hormone and cortisol increased during spring in smolts, but not in parr, peaking just prior to the highest levels of NKAα1b. The results indicate that the increase in the abundance of NKAα1b during smolt development is directly linked to the increase in salinity tolerance that occurs at this stage, but that significant changes also occur after seawater exposure. Spring increases in circulating levels of growth hormone and cortisol indicate that these hormones may be instrumental in upregulating NKAα1b during smolt development.

  11. CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit

    SciTech Connect

    Jiménez-Garza, Octavio; Baccarelli, Andrea A.; Byun, Hyang-Min; Márquez-Gamiño, Sergio; Barrón-Vivanco, Briscia Socorro

    2015-08-01

    Background: CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. Goal: To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. Methods: We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86 +/− 7 mg/m{sup 3}) and 24 administrative workers (reference group, mean levels 0.21 +/− 0.02 mg/m{sup 3}) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes. Results: In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r = − .36, p < 0.05), as well as for IL6 promoter methylation levels (r = .44, p < 0.05). Moreover, CYP2E1 promoter methylation levels where higher in toluene-exposed smokers compared to nonsmokers (p = 0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r = − .37, p < 0.05 and r = − .34, p < 0.05 respectively). Conclusion: These results highlight the importance of considering CYP2E1 epigenetic modifications, as well as its interactions with other genes, as key factors for unraveling the sub cellular mechanisms of toxicity exerted by oxidative stress, which can initiate disease process in chronic, low-level toluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression. - Highlights: • We investigated gene-specific methylation in persons chronically exposed to toluene. • In a previous study, a reduced CYP2E1 activity was observed in these participants. • CYP2E1

  12. Hippocampal cell fate regulation by chronic cocaine during periods of adolescent vulnerability: Consequences of cocaine exposure during adolescence on behavioral despair in adulthood.

    PubMed

    García-Cabrerizo, R; Keller, B; García-Fuster, M J

    2015-09-24

    Given that adolescence represents a critical moment for shaping adult behavior and may predispose to disease vulnerability later in life, the aim of this study was to find a vulnerable period during adolescence in which hippocampal cell fate regulation was altered by cocaine exposure, and to evaluate the long-term consequences of a cocaine experience during adolescence in affecting hippocampal plasticity and behavioral despair in adulthood. Study I: Male rats were treated with cocaine (15mg/kg, i.p.) or saline for 7 consecutive days during adolescence (early post-natal day (PND) 33-39, mid PND 40-46, late PND 47-53). Hippocampal plasticity (i.e., cell fate regulation, cell genesis) was evaluated 24h after the last treatment dose during the course of adolescence (PND 40, PND 47, PND 54). Study II: The consequences of cocaine exposure during adolescence (PND 33-39 or PND 33-46; 7 or 14days) were measured in adulthood at the behavioral (i.e., forced swim test, PND 62-63) and molecular (hippocampal cell markers, PND 64) levels. Chronic cocaine during early adolescence dysregulated FADD forms only in the hippocampus (HC), as compared to other brain regions, and during mid adolescence, impaired cell proliferation (Ki-67) and increased PARP-1 cleavage (a cell death maker) in the HC. Interestingly, chronic cocaine exposure during adolescence did not alter the time adult rats spent immobile in the forced swim test. These results suggest that this paradigm of chronic cocaine administration during adolescence did not contribute to the later manifestation of behavioral despair (i.e., one pro-depressive symptom) as measured by the forced swim test in adulthood. PMID:26215918

  13. Genome-wide alterations in polycomb-regulated epigenomic modifications in embryonic osteoblasts following exposure to maternal obesity in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutritional status during intrauterine and early postnatal life impacts the risk of chronic diseases, presumably via epigenetic mechanisms. However, evidence on the impact of gestational events on regulation of bone development is sparse. Recently we showed that bone development is inhibited in gest...

  14. Consequences of Growing Up Poor.

    ERIC Educational Resources Information Center

    Duncan, Greg J., Ed.; Brooks-Gunn, Jeanne, Ed.

    The consequences and correlates of growing up poor as well as the mechanisms through which poverty influences children are explored. This book is organized with a primary focus on research findings and a secondary concern with policy implications. The chapters are: (1) "Poor Families, Poor Outcomes: The Well-Being of Children and Youth" (Jeanne…

  15. Pattern Recognition Scavenger Receptor A/CD204 Regulates Airway Inflammatory Homeostasis Following Organic Dust Extract Exposures

    PubMed Central

    Poole, Jill A.; Anderson, Leigh; Gleason, Angela M.; West, William W.; Romberger, Debra J.; Wyatt, Todd A.

    2014-01-01

    Exposure to agriculture organic dusts, comprised of a diversity of pathogen-associated molecular patterns, results in chronic airway diseases. The multi-functional class A macrophage scavenger receptor (SRA)/CD204 has emerged as an important class of pattern recognition receptors with broad ligand binding ability. Our objective was to determine the role of SRA in mediating repetitive and post-inflammatory organic dust extract (ODE)-induced airway inflammation. Wild-type (WT) and SRA knockout (KO) mice were intra-nasally treated with ODE or saline daily for 3 wk and immediately euthanized or allowed to recover for 1 wk. Results show that lung histopathologic changes were increased in SRA KO mice as compared to WT following repetitive ODE exposures marked predominately by increased size and distribution of lymphoid aggregates. After a 1-wk recovery from daily ODE treatments, there was significant resolution of lung injury in WT mice, but not SRA KO animals. The increased lung histopathology induced by ODE treatment was associated with decreased accumulation of neutrophils, but greater accumulation of CD4+ T-cells. The lung cytokine milieu induced by ODE was consistent with a TH1/TH17 polarization in both WT and SRA KO mice. Overall, our data demonstrate that SRA/CD204 plays an important role in the normative inflammatory lung response to ODE as evidenced by the enhanced dust-mediated injury viewed in the absence of this receptor. PMID:24491035

  16. Adult longevity of certain mosquito species after larval and pupal exposure to sublethal concentration of an insect growth regulator, hexaflumuron.

    PubMed

    Vasuki, V

    1992-03-01

    Longevity of the adults of three vector species, Culex quinquefasciatus, Anopheles stephensi, and Aedes aegypti was drastically reduced when they were exposed at larval and pupal stages to sublethal concentrations of an insect growth regulator hexaflumuron. When the three species were exposed to 0.05 mg/l at the pupal stage, males and females of Cx. quinquefasciatus suffered a more shortened life span than other species. Among the females whose feeding activity was adversely affected by IGR treatment at the pupal stage, Ae. aegypti showed the minimum survival duration with LT50 of 2.74 days. PMID:1523463

  17. Down-regulation of muscarinic receptors and the m3 subtype in white-footed mice by dietary exposure to parathion

    USGS Publications Warehouse

    Jett, D.A.; Hill, E.F.; Fernando, J.C.; Eldefrawi, M.E.; Eldefrawi, A.T.

    1993-01-01

    The effect of ad libitum dietary exposure (as occurs in the field) to parathion for 14 d was investigated on the muscarinic acetylcholine receptor (mAChR) in brains and submaxillary glands of adults of a field species, the white-footed mouse Peromyscus leucopus. Immunoprecipitation using subtype selective antibodies revealed that the relative ratios of the m1-m5 mAChR subtypes in Peromyscus brain were similar to those in rat brain. There was little variability in acetylcholinesterase (AChE) activity in control mice brains but large variability in 39 exposed mice, resulting from differences in food ingestion and parathion metabolism. Accordingly, data on radioligand binding to mAChRs in each mouse brain were correlated with brain AChE activity in the same mouse, and AChE inhibition served as a biomarker of exposure reflecting in situ paraoxon concentrations. Exposure to parathion for 14 d reduced maximal binding (Bmax) of [3H]quinuclidinyl benzilate ([3H]QNB), [3H]-N-methylscopolamine ([3H]NMS), and [3H]-4-diphenylacetoxy-N-methylpiperidine methiodide ([3H]-4-DAMP) by up to approximately 58% without affecting receptor affinities for these ligands. Maximal reduction in Bmax of [3H]QNB and [3H]-4-DAMP binding occurred in mice with highest AChE inhibition, while equivalent maximal reduction in Bmax of [3H]NMS occurred in mice with only approximately 10% AChE inhibition, without further change at higher parathion doses. This is believed to be due to the hydrophilicity of [3H]NMS, which limits its accessibility to internalized desensitized receptors. In submaxillary glands (mAChRs are predominantly m3 subtype), there were significant dose-dependent reductions in [3H]QNB binding and m3 mRNA levels in exposed mice, revealed by Northern blot analyses. The reduction in m3 receptors is suggested to result mostly from reduced synthesis at the transcription level, rather than from translational or posttranslational events. The data suggest that down-regulation of mAChRs occurs

  18. Cardiac fibrosis and down regulation of GLUT4 in experimental diabetic cardiomyopathy are ameliorated by chronic exposures to intermittent altitude

    PubMed Central

    Faramoushi, Mahdi; Amir Sasan, Ramin; Sari Sarraf, Vahid; Karimi, Pouran

    2016-01-01

    Introduction: Chronic intermittent hypoxia is considered as a preconditioning status in cardiovascular health to inducing resistance to the low oxygen supply. Diabetic cardiomyopathy leads to inability of the heart to effective circulation of blood preventing of consequent tissue damages so; the aim of this study was elucidation of effect of chronic exposure to hypoxia on Cardiac fibrosis and expression of GLUT4 in experimental diabetic cardiomyopathy. Methods: A total number of 30 rats were randomly divided into three groups; 1: Normoxia control group (NN, n = 10). 2: Normoxia diabetic group (ND, n = 10) that took fat diet for 2 weeks then were injected by streptozotocin (37 mg/kg) and 3: Hypoxia diabetic group (HD, n = 10): that were exposed to chronic intermittent hypoxia (CIH) (altitude ≈3400 m, 14% oxygen for 8 weeks). After hypoxia challenge, plasma metabolic parameters including: fasting blood glucose (FBS), triglyceride (TG) and total cholesterol (TC) were measured by colorimetric assay. Cardiac expression of GLUT4 protein and cardiac collagen accumulation were determined in the excised left ventricle by western blotting, and Masson trichrome staining respectively. Results: Based on resultant data, FBS, TG and TC were significantly (P < 0.05) decreased in HD vs. ND. Homeostasis Model Assessment (HOMA) were also significantly attenuated after exposed to CIH in HD group compared to ND group (P < 0.05). Significant increase in packed cell volume and hemoglobin concentration was observed in HD group compared to ND group (P < 0.05). Comparison of heart wet weight between three groups showed a significant difference (P < 0.05) with lower amount in HD and ND versus NN. Myocardial fibrosis was significantly more pronounced in ND when compared to NN. Eight weeks exposure to hypoxia ameliorated this increase in HD group. Intermittent hypoxia significantly increased GLUT4 protein expression in HD compared to ND group (P < 0.05). Conclusion: Data suggested that CIH

  19. The cell cycle inhibitor Cdkn1a regulates Langerhans cell radiation resistance and promotes T regulatory cell generation upon exposure to ionizing irradiation

    PubMed Central

    Price, Jeremy G.; Idoyaga, Juliana; Salmon, Hélène; Hogstad, Brandon; Bigarella, Carolina L.; Ghaffari, Saghi; Leboeuf, Marylene; Merad, Miriam

    2015-01-01

    Treatment with ionizing irradiation (IR) may lead to accumulation of tumor-infiltrating T regulatory (Treg) cells and subsequent tumor resistance to radiotherapy. Here we focused on the contribution of the epidermal mononuclear phagocytes, Langerhans cells (LCs), to this phenomenon because of their ability to resist depletion by high-dose IR. We found that LCs resisted apoptosis and rapidly repaired DNA damage post-IR. Particularly, we found that CDKN1A (cyclin-dependent kinase inhibitor 1A, also known as p21) was overexpressed in LCs, and that Cdkn1a−/− LCs underwent apoptosis and accumulated DNA damage following IR treatment. Wild-type, but not Cdkn1a−/−, LCs up-regulated major histocompatibility complex class II molecules, migrated to the draining lymph nodes and increased Treg cell numbers upon exposure to IR. These findings suggest a means for manipulating LC IR-resistance to increase cutaneous tumor response to radiotherapy. PMID:26343536

  20. Tumor Protein (TP)-p53 Members as Regulators of Autophagy in Tumor Cells upon Marine Drug Exposure.

    PubMed

    Ratovitski, Edward A

    2016-01-01

    Targeting autophagic pathways might play a critical role in designing novel chemotherapeutic approaches in the treatment of human cancers, and the prevention of tumor-derived chemoresistance. Marine compounds were found to decrease tumor cell growth in vitro and in vivo. Some of them were shown to induce autophagic flux in tumor cells. In this study, we observed that the selected marine life-derived compounds (Chromomycin A2, Psammaplin A, and Ilimaquinone) induce expression of several autophagic signaling intermediates in human squamous cell carcinoma, glioblastoma, and colorectal carcinoma cells in vitro through a transcriptional regulation by tumor protein (TP)-p53 family members. These conclusions were supported by specific qPCR expression analysis, luciferase reporter promoter assay, and chromatin immunoprecipitation of promoter sequences bound to the TP53 family proteins, and silencing of the TP53 members in tumor cells. PMID:27537898

  1. Non-invasive assessment of Alterations in Cardiovascular regulation and function and susceptibility to ventricular arrhythmias resulting from microgravity exposure

    NASA Astrophysics Data System (ADS)

    Ramsdell, Craig D.; Sundby, Grete H.; Sherman, Derin; Maa, Ming; Baskin, Jacquelyn L.; Williams, Gordon H.; Cohen, Richard J.

    2000-01-01

    Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps as a result, fully effective countermeasures have yet to be developed. The National Space Biomedical Research Institute Cardiovascular Alterations Team is currently conducting a head-down tilt bed rest study in Boston. These studies involve the application of two powerful new methodologies developed at the NASA Center for Quantitative Cardiovascular Physiology, Modeling and Data Analysis at the Massachusetts Institute of Technology-cardiovascular system identification and T Wave Alternans analysis-for the study of the effects of simulated microgravity on the cardiovascular system. This study is being used as a basis for developing effective countermeasures against microgravity induced orthostatic hypotension and ventricular arrhythmias. .

  2. Tumor Protein (TP)-p53 Members as Regulators of Autophagy in Tumor Cells upon Marine Drug Exposure

    PubMed Central

    Ratovitski, Edward A.

    2016-01-01

    Targeting autophagic pathways might play a critical role in designing novel chemotherapeutic approaches in the treatment of human cancers, and the prevention of tumor-derived chemoresistance. Marine compounds were found to decrease tumor cell growth in vitro and in vivo. Some of them were shown to induce autophagic flux in tumor cells. In this study, we observed that the selected marine life-derived compounds (Chromomycin A2, Psammaplin A, and Ilimaquinone) induce expression of several autophagic signaling intermediates in human squamous cell carcinoma, glioblastoma, and colorectal carcinoma cells in vitro through a transcriptional regulation by tumor protein (TP)-p53 family members. These conclusions were supported by specific qPCR expression analysis, luciferase reporter promoter assay, and chromatin immunoprecipitation of promoter sequences bound to the TP53 family proteins, and silencing of the TP53 members in tumor cells. PMID:27537898

  3. Different Regulation of p53 Expression by Cadmium Exposure in Kidney, Liver, Intestine, Vasculature, and Brain Astrocytes

    PubMed Central

    Lee, Jin-Yong; Tokumoto, Maki; Hattori, Yuta; Fujiwara, Yasuyuki; Shimada, Akinori; Satoh, Masahiko

    2016-01-01

    Chronic exposure to cadmium (Cd) is known to adversely affect renal function. Our previous studies indicated that Cd induces p53-dependent apoptosis by inhibiting gene expression of the ubiquitin-conjugating enzyme (Ube) 2d family in both human and rat proximal tubular cells. In this study, the effects of Cd on protein expression of p53 and apoptotic signals in the kidney and liver of mice exposed to Cd for 12 months were examined, as well as the effects of Cd on p53 protein levels and gene expression of the Ube2d family in various cell lines. Results showed that in the kidney of mice exposed to 300 ppm Cd for 12 months, there was overaccumulation of p53 proteins in addition to the induction of apoptosis, which was triggered specifically in the proximal tubules. Interestingly, the site of apoptosis was the same as that of p53 accumulation in the proximal tubules. In the liver of mice chronically exposed to Cd, gene expression of the Ube2d family tended to be slightly decreased, together with slight apoptosis without the accumulation of p53 protein. In rat small intestine epithelial (IEC-6) cells, Cd decreased not only the p53 protein level but also gene expression of Ube2d1, Ube2d2 and Ube2d4. In human brain microvascular endothelial cells (HBMECs), Cd did not suppress gene expression of the Ube2d family, but increased the p53 protein level. In human brain astrocytes (HBASTs), Cd only increased gene expression of UBE2D3. These results suggest that Cd-induced apoptosis through p53 protein is associated with renal toxicity but not hepatic toxicity, and the modification of p53 protein by Cd may vary depending on cell type. PMID:26977261

  4. Up-regulation of nucleotide excision repair in mouse lung and liver following chronic exposure to aflatoxin B{sub 1} and its dependence on p53 genotype

    SciTech Connect

    Mulder, Jeanne E.; Bondy, Genevieve S.; Mehta, Rekha; Massey, Thomas E.

    2014-03-01

    Aflatoxin B{sub 1} (AFB{sub 1}) is biotransformed in vivo into an epoxide metabolite that forms DNA adducts that may induce cancer if not repaired. p53 is a tumor suppressor gene implicated in the regulation of global nucleotide excision repair (NER). Male heterozygous p53 knockout (B6.129-Trp53{sup tm1Brd}N5, Taconic) and wild-type mice were exposed to 0, 0.2 or 1.0 ppm AFB{sub 1} for 26 weeks. NER activity was assessed with an in vitro assay, using AFB{sub 1}-epoxide adducted plasmid DNA as a substrate. For wild-type mice, repair of AFB{sub 1}–N7-Gua adducts was 124% and 96% greater in lung extracts from mice exposed to 0.2 ppm and 1.0 ppm AFB{sub 1} respectively, and 224% greater in liver extracts from mice exposed to 0.2 ppm AFB{sub 1} (p < 0.05). In heterozygous p53 knockout mice, repair of AFB{sub 1}–N7-Gua was only 45% greater in lung extracts from mice exposed to 0.2 ppm AFB{sub 1} (p < 0.05), and no effect was observed in lung extracts from mice treated with 1.0 ppm AFB{sub 1} or in liver extracts from mice treated with either AFB{sub 1} concentration. p53 genotype did not affect basal levels of repair. AFB{sub 1} exposure did not alter repair of AFB{sub 1}-derived formamidopyrimidine adducts in lung or liver extracts of either mouse genotype nor did it affect XPA or XPB protein levels. In summary, chronic exposure to AFB{sub 1} increased NER activity in wild-type mice, and this response was diminished in heterozygous p53 knockout mice, indicating that loss of one allele of p53 limits the ability of NER to be up-regulated in response to DNA damage. - Highlights: • Mice are chronically exposed to low doses of the mycotoxin aflatoxin B{sub 1} (AFB{sub 1}). • The effects of AFB{sub 1} and p53 status on nucleotide excision repair are investigated. • AFB{sub 1} increases nucleotide excision repair in wild type mouse lung and liver. • This increase is attenuated in p53 heterozygous mouse lung and liver. • Results portray the role of p53 in

  5. Forgotten Americans: The "Working Poor."

    ERIC Educational Resources Information Center

    Joe, Tom

    1984-01-01

    The working poor are employable people who have found low-paying jobs and barely scrape out a living. By removing many forms of federal aid, the Reagan administration has locked the working poor into poverty. In saving a few dollars today, we are penalizing the next generation. (CS)

  6. Effects of chronic exposure to tributyltin on tissue-specific cytochrome P450 1 regulation in juvenile common carp.

    PubMed

    Li, Zhi-Hua; Zhong, Li-Qiao; Mu, Wei-Na; Wu, Yan-Hua

    2016-06-01

    1. The purpose of this study was to compare tributyltin (TBT)-induced cytochrome P450 1 (CYP450 1) regulation in liver, gills and muscle of juvenile common carp (Cyprinus carpio). 2. Fish were exposed to sublethal concentrations of TBT (75, 0.75 and 7.5 μg/L) for 60 days. CYP450 1A was measured at the enzyme activity level as 7-ethoxyresorufin-O-deethylase (EROD) activity, as well as the mRNA expression of CYP450 1 family genes (CYP1A, CYP1B, CYP1C1 and CYP1C2) in fish tissues. 3. Based on the results, the liver displayed the highest absolute levels of EROD activity, both under nonexposed and exposed conditions. Additional, EROD activities and CYP1A gene levels showed a good correlation in all three organs. According to the mRNA expression of CYP450 1 family genes, it suggested that CYP1A was to accommodate most EROD activity in fish, but other CYP450 forms also involved in this proceeding. 4. Overall, the study revealed both similarities and differences in the concentration-dependent CYP450 1 responses of the three target organs, which could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity. PMID:26446983

  7. Ethanol Exposure Induces Neonatal Neurodegeneration by Enhancing CB1R Exon1 Histone H4K8 Acetylation and Up-regulating CB1R Function causing Neurobehavioral Abnormalities in Adult Mice

    PubMed Central

    Subbanna, Shivakumar; Nagre, Nagaraja N.; Umapathy, Nagavedi S.; Pace, Betty S.

    2015-01-01

    Background: Ethanol exposure to rodents during postnatal day 7 (P7), which is comparable to the third trimester of human pregnancy, induces long-term potentiation and memory deficits. However, the molecular mechanisms underlying these deficits are still poorly understood. Methods: In the present study, we explored the potential role of epigenetic changes at cannabinoid type 1 (CB1R) exon1 and additional CB1R functions, which could promote memory deficits in animal models of fetal alcohol spectrum disorder. Results: We found that ethanol treatment of P7 mice enhances acetylation of H4 on lysine 8 (H4K8ace) at CB1R exon1, CB1R binding as well as the CB1R agonist-stimulated GTPγS binding in the hippocampus and neocortex, two brain regions that are vulnerable to ethanol at P7 and are important for memory formation and storage, respectively. We also found that ethanol inhibits cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation and activity-regulated cytoskeleton-associated protein (Arc) expression in neonatal and adult mice. The blockade or genetic deletion of CB1Rs prior to ethanol treatment at P7 rescued CREB phosphorylation and Arc expression. CB1R knockout mice exhibited neither ethanol-induced neurodegeneration nor inhibition of CREB phosphorylation or Arc expression. However, both neonatal and adult mice did exhibit enhanced CREB phosphorylation and Arc protein expression. P7 ethanol-treated adult mice exhibited impaired spatial and social recognition memory, which were prevented by the pharmacological blockade or deletion of CB1Rs at P7. Conclusions: Together, these findings suggest that P7 ethanol treatment induces CB1R expression through epigenetic modification of the CB1R gene, and that the enhanced CB1R function induces pCREB, Arc, spatial, and social memory deficits in adult mice. PMID:25609594

  8. Pharyngeal pumping inhibition and avoidance by acute exposure to high CO2 levels are both regulated by the BAG neurons via different molecular pathways.

    PubMed

    Sharabi, Kfir; Charar, Chayki; Gruenbaum, Yosef

    2015-01-01

    Carbon dioxide (CO2) is a key molecule in many biological processes. Studies in humans, mice, D. melanogaster, C. elegans, unicellular organisms and plants have shed light on the molecular pathways activated by elevated levels of CO2. However, the mechanisms that organisms use to sense and respond to high CO2 levels remain largely unknown. Previous work has shown that C. elegans quickly avoid elevated CO2 levels using mechanisms that involve the BAG, ASE and AFD neurons via cGMP- and calcium- signaling pathways. Here, we discuss our recent finding that exposure of C. elegans to high CO2 levels leads to a very rapid cessation in the contraction of the pharynx muscles. Surprisingly, none of the tested CO2 avoidance mutants affected the rapid pumping inhibition response to elevated CO2 levels. A forward genetic screen identified that the hid-1-mediated pathway of dense core vesicle maturation regulates the pumping inhibition, probably through affecting neuropeptide secretion. Genetic studies and laser ablation experiments showed that the CO2 response of the pharyngeal muscle pumping is regulated by the BAG neurons, the same neurons that mediate CO2 avoidance. PMID:26430557

  9. Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit.

    PubMed

    Kitamura, Yoshiaki; Nakagawa, Hideyuki; Fujii, Tatsuya; Sakoda, Takema; Enomoto, Tadao; Mizuguchi, Hiroyuki; Fukui, Hiroyuki; Takeda, Noriaki

    2015-11-01

    In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders. PMID:26598006

  10. Effects of In Vitro Exposure to Diarrheic Toxin Producer Prorocentrum lima on Gene Expressions Related to Cell Cycle Regulation and Immune Response in Crassostrea gigas

    PubMed Central

    de Jesús Romero-Geraldo, Reyna; García-Lagunas, Norma; Hernández-Saavedra, Norma Yolanda

    2014-01-01

    Background Crassostrea gigas accumulates diarrheic shellfish toxins (DSP) associated to Prorocentrum lima of which Okadaic acid (OA) causes specific inhibitions of serine and threonine phosphatases 1 and 2A. Its toxic effects have been extensively reported in bivalve mollusks at cellular and physiological levels, but genomic approaches have been scarcely studied. Methodology/Principal Findings Acute and sub-chronic exposure effects of P. lima were investigated on farmed juvenile C. gigas (3–5 mm). The Pacific oysters were fed with three dinoflagellate concentrations: 0.3, 3, and 30×103 cells mL−1 along with a nontoxic control diet of Isochrysis galbana. The effects of P. lima on C. gigas were followed by analyzing expression levels of a total of four genes, three involved in cell cycle regulation and one in immune response by polymerase chain reaction and real time quantitative PCR, where changes in time and cell concentration were found. The highest expression levels were found in oysters fed 3×103 cells mL−1 at 168 h for the cycle regulator p21 protein (9 fold), chromatin assembly factor 1 p55 subunit (8 fold), elongation factor 2 (2 fold), and lipopolysaccharide/β-1, 3 glucan binding protein (13 fold above base line). Additionally, the transcript level of all the genes decreased in oysters fed wich the mixed diet 30×103 cells mL−1 of dinoflagellate after 72 h and was lowest in the chromatin assembly factor 1 p55 subunit (0.9 fold below baseline). Conclusions On C. gigas the whole cell ingestion of P lima caused a clear mRNA modulation expression of the genes involved in cell cycle regulation and immune system. Over-expression could be related to DNA damage, disturbances in cell cycle continuity, probably a genotoxic effect, as well as an activation of its innate immune system as first line of defense. PMID:24825133

  11. Prolonged exposure of chromaffin cells to nitric oxide down-regulates the activity of soluble guanylyl cyclase and corresponding mRNA and protein levels

    PubMed Central

    Ferrero, Rut; Torres, Magdalena

    2002-01-01

    Background Soluble guanylyl cyclase (sGC) is the main receptor for nitric oxide (NO) when the latter is produced at low concentrations. This enzyme exists mainly as a heterodimer consisting of one α and one β subunit and converts GTP to the second intracellular messenger cGMP. In turn, cGMP plays a key role in regulating several physiological processes in the nervous system. The aim of the present study was to explore the effects of a NO donor on sGC activity and its protein and subunit mRNA levels in a neural cell model. Results Continuous exposure of bovine adrenal chromaffin cells in culture to the nitric oxide donor, diethylenetriamine NONOate (DETA/NO), resulted in a lower capacity of the cells to synthesize cGMP in response to a subsequent NO stimulus. This effect was not prevented by an increase of intracellular reduced glutathione level. DETA/NO treatment decreased sGC subunit mRNA and β1 subunit protein levels. Both sGC activity and β1 subunit levels decreased more rapidly in chromaffin cells exposed to NO than in cells exposed to the protein synthesis inhibitor, cycloheximide, suggesting that NO decreases β1 subunit stability. The presence of cGMP-dependent protein kinase (PKG) inhibitors effectively prevented the DETA/NO-induced down regulation of sGC subunit mRNA and partially inhibited the reduction in β1 subunits. Conclusions These results suggest that activation of PKG mediates the drop in sGC subunit mRNA levels, and that NO down-regulates sGC activity by decreasing subunit mRNA levels through a cGMP-dependent mechanism, and by reducing β1 subunit stability. PMID:12350235

  12. Second-hand smoke exposure in indoor and outdoor areas of cafés and restaurants: Need for extending smoking regulation outdoors?

    PubMed

    Fu, Marcela; Fernández, Esteve; Martínez-Sánchez, Jose M; San Emeterio, Noemi; Quirós, Nuria; Sureda, Xisca; Ballbè, Montse; Muñoz, Glòria; Riccobene, Anna; Centrich, Francesc; Saltó, Esteve; López, María J

    2016-07-01

    Smoke-free legislation in indoor public places has concentrated smokers in the areas outside building entrances or other outdoor areas. This study assessed the drift of second-hand smoke between outdoor and indoor areas of cafés and restaurants in Barcelona, Spain, and characterized the exposure on outdoor terraces. Using a cross-sectional design, we monitored vapor-phase nicotine in indoor areas and outside entrances simultaneously (n=47), and on some outdoor terraces (n=51). We computed the median nicotine concentration and interquartile range (IQR) to describe the data and performed multivariate analysis to describe nicotine concentration and its determinants. The overall median nicotine concentration indoors was 0.65µg/m(3) (IQR: 0.29-1.17µg/m(3)), with significant differences based on the number of smokers at the entrance (p=0.039). At outside entrances, the overall median nicotine concentration was 0.41µg/m(3) (IQR: 0.21-1.17µg/m(3)). The nicotine concentrations indoors and at the corresponding outside entrances were not significantly different, and the multivariate analysis confirmed the relationship between these variables. On terraces, the overall median nicotine concentration was 0.54µg/m(3) (IQR: 0.25-1.14µg/m(3)), but it increased to 0.60µg/m(3) when a tobacco smell was perceived, 0.72µg/m(3) on closed terraces, 1.24µg/m(3) when there were >6 smokers, and 1.24µg/m(3) when someone smoked >20min. Multivariate analysis confirmed the outdoor terrace area, the season, the type of enclosure, and the number of smokers as the most relevant variables explaining nicotine concentration (R(2)=0.396). These findings show that second-hand smoke exposure exists in indoor areas due to smokers smoking at the outside entrances. In addition, exposure may occur on outdoor terraces when smokers are present and the terrace is enclosed to some extent. Thus, the current Spanish law does not fully protect non-smokers from second-hand smoke and supports extending

  13. Role of MAP kinases in regulating expression of antioxidants and inflammatory mediators in mouse keratinocytes following exposure to the half mustard, 2-chloroethyl ethyl sulfide

    SciTech Connect

    Black, Adrienne T.; Joseph, Laurie B.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

    2010-06-15

    Dermal exposure to sulfur mustard causes inflammation and tissue injury. This is associated with changes in expression of antioxidants and eicosanoids which contribute to oxidative stress and toxicity. In the present studies we analyzed mechanisms regulating expression of these mediators using an in vitro skin construct model in which mouse keratinocytes were grown at an air-liquid interface and exposed directly to 2-chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant. CEES (100-1000 {mu}M) was found to cause marked increases in keratinocyte protein carbonyls, a marker of oxidative stress. This was correlated with increases in expression of Cu,Zn superoxide dismutase, catalase, thioredoxin reductase and the glutathione S-transferases, GSTA1-2, GSTP1 and mGST2. CEES also upregulated several enzymes important in the synthesis of prostaglandins and leukotrienes including cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-2 (mPGES-2), prostaglandin D synthase (PGDS), 5-lipoxygenase (5-LOX), leukotriene A{sub 4} (LTA{sub 4}) hydrolase and leukotriene C{sub 4} (LTC{sub 4}) synthase. CEES readily activated keratinocyte JNK and p38 MAP kinases, signaling pathways which are known to regulate expression of antioxidants, as well as prostaglandin and leukotriene synthases. Inhibition of p38 MAP kinase suppressed CEES-induced expression of GSTA1-2, COX-2, mPGES-2, PGDS, 5-LOX, LTA{sub 4} hydrolase and LTC{sub 4} synthase, while JNK inhibition blocked PGDS and GSTP1. These data indicate that CEES modulates expression of antioxidants and enzymes producing inflammatory mediators by distinct mechanisms. Increases in antioxidants may be an adaptive process to limit tissue damage. Inhibiting the capacity of keratinocytes to generate eicosanoids may be important in limiting inflammation and protecting the skin from vesicant-induced oxidative stress and injury.

  14. The dormancy-breaking stimuli "chilling, hypoxia and cyanamide exposure" up-regulate the expression of α-amylase genes in grapevine buds.

    PubMed

    Rubio, Sebastián; Donoso, Amanda; Pérez, Francisco J

    2014-03-15

    It has been suggested that respiratory stress is involved in the mechanism underlying the dormancy-breaking effect of hydrogen cyanamide (H2CN2) and sodium azide in grapevine buds; indeed, reductions in oxygen levels (hypoxia) and inhibitors of respiration promote bud-break in grapevines. In this study, we showed that, hypoxia increased starch hydrolysis soluble sugar consumption and up-regulated the expression of α-amylase genes (Vvα-AMYs) in grapevine buds, suggesting that these biochemical changes induced by hypoxia, may play a relevant role in the release of buds from endodormancy (ED). Three of the four Vvα-AMY genes that are expressed in grapevine buds were up-regulated by hypoxia and a correlation between changes in sugar content and level of Vvα-AMY gene expression during the hypoxia treatment was found, suggesting that soluble sugars mediate the effect of hypoxia on Vvα-AMY gene expression. Exogenous applications of soluble sugars and sugar analogs confirmed this finding and revealed that osmotic stress induces the expression of Vvα-AMY1 and Vvα-AMY3 and that soluble sugars induces Vvα-AMY2 and Vvα-AMY4 gene expression. Interestingly, the plant hormone gibberellic acid (GA3) induced the expression of Vvα-AMY3 and Vvα-AMY4 genes, while dormancy breaking stimuli, chilling and cyanamide exposure, mainly induced the expression of Vvα-AMY1 and Vvα-AMY2 genes, suggesting that these two α-amylase genes might be involved in the release of grapevine buds from the ED. PMID:24594388

  15. Poor smokers, poor quitters, and cigarette tax regressivity.

    PubMed

    Remler, Dahlia K

    2004-02-01

    The traditional view that excise taxes are regressive has been challenged. I document the history of the term regressive tax, show that traditional definitions have always found cigarette taxes to be regressive, and illustrate the implications of the greater price responsiveness observed among the poor. I explain the different definitions of tax burden: accounting, welfare-based willingness to pay, and welfare-based time inconsistent. Progressivity (equity across income groups) is sensitive to the way in which tax burden is assessed. Analysis of horizontal equity (fairness within a given income group) shows that cigarette taxes heavily burden poor smokers who do not quit, no matter how tax burden is assessed. PMID:14759931

  16. A MICROARRAY ANALYSIS OF GENE EXPRESSION IN THE EMBRYONIC FORELIMB OF THE C57BL/6J MOUSE REVEALS SIGNIFICANT ALTERATIONS METABOLIC AND DEVELOPMENTAL REGULATION FOLLOWING ETHANOL EXPOSURE.

    EPA Science Inventory

    The observation of transcriptional changes following embryonic ethanol exposure may provide significant insights into the biological response to ethanol exposure. In this study, we used microarray analysis to examine the transcriptional response of the developing limb to a dose ...

  17. Exposure to Diflubenzuron Results in an Up-Regulation of a Chitin Synthase 1 Gene in Citrus Red Mite, Panonychus citri (Acari: Tetranychidae)

    PubMed Central

    Xia, Wen-Kai; Ding, Tian-Bo; Niu, Jin-Zhi; Liao, Chong-Yu; Zhong, Rui; Yang, Wen-Jia; Liu, Bin; Dou, Wei; Wang, Jin-Jun

    2014-01-01

    Chitin synthase synthesizes chitin, which is critical for the arthropod exoskeleton. In this study, we cloned the cDNA sequences of a chitin synthase 1 gene, PcCHS1, in the citrus red mite, Panonychus citri (McGregor), which is one of the most economically important pests of citrus worldwide. The full-length cDNA of PcCHS1 contains an open reading frame of 4605 bp of nucleotides, which encodes a protein of 1535 amino acid residues with a predicted molecular mass of 175.0 kDa. A phylogenetic analysis showed that PcCHS1 was most closely related to CHS1 from Tetranychus urticae. During P. citri development, PcCHS1 was constantly expressed in all stages but highly expressed in the egg stage (114.8-fold higher than in the adult). When larvae were exposed to diflubenzuron (DFB) for 6 h, the mite had a significantly high mortality rate, and the mRNA expression levels of PcCHS1 were significantly enhanced. These results indicate a promising use of DFB to control P. citri, by possibly acting as an inhibitor in chitin synthesis as indicated by the up-regulation of PcCHS1 after exposure to DFB. PMID:24590130

  18. Exposure to diflubenzuron results in an up-regulation of a chitin synthase 1 gene in citrus red mite, Panonychus citri (Acari: Tetranychidae).

    PubMed

    Xia, Wen-Kai; Ding, Tian-Bo; Niu, Jin-Zhi; Liao, Chong-Yu; Zhong, Rui; Yang, Wen-Jia; Liu, Bin; Dou, Wei; Wang, Jin-Jun

    2014-01-01

    Chitin synthase synthesizes chitin, which is critical for the arthropod exoskeleton. In this study, we cloned the cDNA sequences of a chitin synthase 1 gene, PcCHS1, in the citrus red mite, Panonychus citri (McGregor), which is one of the most economically important pests of citrus worldwide. The full-length cDNA of PcCHS1 contains an open reading frame of 4605 bp of nucleotides, which encodes a protein of 1535 amino acid residues with a predicted molecular mass of 175.0 kDa. A phylogenetic analysis showed that PcCHS1 was most closely related to CHS1 from Tetranychus urticae. During P. citri development, PcCHS1 was constantly expressed in all stages but highly expressed in the egg stage (114.8-fold higher than in the adult). When larvae were exposed to diflubenzuron (DFB) for 6 h, the mite had a significantly high mortality rate, and the mRNA expression levels of PcCHS1 were significantly enhanced. These results indicate a promising use of DFB to control P. citri, by possibly acting as an inhibitor in chitin synthesis as indicated by the up-regulation of PcCHS1 after exposure to DFB. PMID:24590130

  19. Negative regulation of the FOXO3a transcription factor by mTORC2 induces a pro-survival response following exposure to ultraviolet-B irradiation.

    PubMed

    Feehan, Robert P; Shantz, Lisa M

    2016-08-01

    Exposure to ultraviolet-B (UVB) irradiation, the principal cause of non-melanoma skin cancer (NMSC), activates both the rapamycin-sensitive mammalian target of rapamycin complex 1 (mTORC1) and the rapamycin-resistant mTORC2. We have previously reported that UVB-induced keratinocyte survival is dependent on mTORC2, though the specific mechanism is not well understood. FOXO3a is an important transcription factor involved in regulating cell survival. The activity of FOXO3a is reduced as a result of protein kinase B (AKT/PKB) activation, which is downstream of mTORC2; however, the specific function of FOXO3a during UVB-induced apoptosis is unclear. In this study, we establish that in cells with wild-type mTORC2 activity, FOXO3a is quickly phosphorylated in response to UVB and sequestered in the cytoplasm. In contrast, loss of mTORC2 causes FOXO3a to be localized to the nucleus and sensitizes cells to UVB-induced apoptosis. Furthermore, this sensitization is rescued by knockdown of FOXO3a. Taken together, these studies provide strong evidence that inhibition of mTORC2 enhances UVB-induced apoptosis in a FOXO3a-dependent manner, and suggest that FOXO3a activation by mTORC2 inhibitors may be a valuable chemopreventive target in NMSC. PMID:27058291

  20. Basal regulation of HPA and dopamine systems is altered differentially in males and females by prenatal alcohol exposure and chronic variable stress

    PubMed Central

    Uban, Kristina A.; Comeau, Wendy; Ellis, Linda A.; Galea, Liisa A. M.; Weinberg, Joanne

    2013-01-01

    Effects of prenatal alcohol exposure (PAE) on central nervous system function include an increased prevalence of mental health problems, including substance use disorders (SUD). The hypothalamic-pituitary-adrenal (HPA) and dopamine systems have overlapping neurocircuitries and are both implicated in SUD. PAE alters both HPA and dopaminergic activity and regulation, resulting in increased HPA tone and an overall reduction in tonic dopamine activity. However, effects of PAE on the interaction between HPA and dopamine (DA) systems have not been investigated. The present study examined PAE effects on basal regulation of central stress and dopamine systems in key brain regions where these systems intersect. Adult Sprague-Dawley male and female offspring from prenatal alcohol-exposed (PAE), pairfed (PF), and ad libitum-fed control (C) groups were subjected to chronic variable stress (CVS) or remained as a no stress (non-CVS) control group. Corticotropin releasing hormone (CRH) mRNA, as well as glucocorticoid and DA receptor (DA-R) expression were measured under basal conditions 24 hours following the end of CVS. We show, for the first time, that regulation of basal HPA and DA systems, and likely, HPA-DA interactions, are altered differentially in males and females by PAE and CVS. PAE augmented the typical attenuation in weight gain during CVS in males and caused increased weight loss in females. Increased basal corticosterone levels in control, but not PAE, females suggest that PAE alters the profile of basal hormone secretion throughout CVS. CVS downregulated basal CRH mRNA in the prefrontal cortex and throughout the bed nucleus of the stria terminalis (BNST) in PAE females but only in the posterior BNST of control females. PAE males and females exposed to CVS exhibited more widespread upregulation of basal mineralocorticoid receptor (MR) mRNA throughout the hippocampus, and an attenuated decrease in DA-R expression throughout the nucleus accumbens and striatum compared

  1. Are Poor Chinese Text Comprehenders Also Poor in Written Composition?

    ERIC Educational Resources Information Center

    Guan, Connie Qun; Ye, Feifei; Meng, Wanjin; Leong, Che Kan

    2013-01-01

    We studied the performance in three genres of Chinese written composition (narration, exposition, and argumentation) of 158 grade 4, 5, and 6 poor Chinese text comprehenders compared with 156 good Chinese text comprehenders. We examined text comprehension and written composition relationship. Verbal working memory (verbal span working memory and…

  2. The management of poor performance

    PubMed Central

    Mayberry, John F

    2007-01-01

    Identification of poor performance is in an integral part of government policy. The suggested approach for the identification of such problems, advocated by the General Medical Council, is that of appraisal. However, traditionally, there has been a reluctance to deal with poor performers, as all doctors have made mistakes and are usually only too ready to forgive and be non‐critical of colleagues. The problems are widespread, and 6% of the senior hospital workforce in any 5‐year period may have problems. PMID:17308213

  3. Prospects for the Working Poor

    ERIC Educational Resources Information Center

    Miller, S. M.

    1970-01-01

    Based on a chapter entitled "Barriers to Employment of the Disadvantaged by Martin Deutsch and S. M. Miller in "Manpower Report of the President, 1968. Discusses the Nixon proposals for remediating poverty in relation to the socioeconomic factors operating to maintain the condition of being poor while working. (JM)

  4. Poor Memory: A Case Report.

    ERIC Educational Resources Information Center

    Meltzer, Malcolm L.

    1983-01-01

    Presents a case study of a person who had a cardiac arrest with some right-sided brain damage. Describes the effects of poor memory on cognition, personality, and interpersonal relationships based on personal observations during memory impairment. Highlights the course of rehabilitation over a two-year period. (PAS)

  5. Are poor Chinese text comprehenders also poor in written composition?

    PubMed

    Guan, Connie Qun; Ye, Feifei; Meng, Wanjin; Leong, Che Kan

    2013-10-01

    We studied the performance in three genres of Chinese written composition (narration, exposition, and argumentation) of 158 grade 4, 5, and 6 poor Chinese text comprehenders compared with 156 good Chinese text comprehenders. We examined text comprehension and written composition relationship. Verbal working memory (verbal span working memory and operation span working memory) and different levels of linguistic tasks-morphological sensitivity (morphological compounding and morphological chain), sentence processing (syntax construction and syntax integrity), and text comprehension (narrative and expository texts)-were used to predict separately narrative, expository, and argumentation written compositions in these students. Grade for grade, the good text comprehenders outperformed the poor text comprehenders in all tasks, except for morphological chain. Hierarchical multiple regression analyses showed differential contribution of the tasks to different genres of writing. In particular, text comprehension made unique contribution to argumentation writing in the poor text comprehenders. Future studies should ask students to read and write parallel passages in the same genre for better comparison and incorporate both instructional and motivational variables. PMID:23666849

  6. Estrogen Sensitivity of Target Genes and Expression of Nuclear Receptor Co-Regulators in Rat Prostate after Pre- and Postnatal Exposure to the Ultraviolet Filter 4-Methylbenzylidene Camphor

    PubMed Central

    Durrer, Stefan; Ehnes, Colin; Fuetsch, Michaela; Maerkel, Kirsten; Schlumpf, Margret; Lichtensteiger, Walter

    2007-01-01

    Background and objectives In previous studies, we found that the ultraviolet filter 4-methyl-benzylidene camphor (4-MBC) exhibits estrogenic activity, is a preferential estrogen receptor (ER)-β ligand, and interferes with development of female reproductive organs and brain of both sexes in rats. Here, we report effects on male development. Methods 4-MBC (0.7, 7, 24, 47 mg/kg/day) was administered in chow to the parent generation before mating, during gestation and lactation, and to offspring until adulthood. mRNA was determined in prostate lobes by real-time reverse transcription–polymerase chain reaction and protein was determined by Western blot analysis. Results 4-MBC delayed male puberty, decreased adult prostate weight, and slightly increased testis weight. Androgen receptor (AR), insulin-like growth factor-1 (IGF-1), ER-α, and ER-β expression in prostate were altered at mRNA and protein levels, with stronger effects in dorsolateral than ventral prostate. To assess sensitivity of target genes to estrogens, offspring were castrated on postnatal day 70, injected with 17β-estradiol (E2; 10 or 50 μg/kg, sc) or vehicle on postnatal day 84, and sacrificed 6 hr later. Acute repression of AR and IGF-1 mRNAs by E2, studied in ventral prostate, was reduced by 4-MBC exposure. This was accompanied by reduced co-repressor N-CoR (nuclear receptor co-repressor) protein in ventral and dorsolateral prostate, whereas steroid receptor coactivator-1 (SRC-1) protein levels were unaffected. Conclusions Our data indicate that 4-MBC affects development of male reproductive functions and organs, with a lowest observed adverse effect level of 0.7 mg/kg. Nuclear receptor coregulators were revealed as targets for endocrine disruptors, as shown for N-CoR in prostate and SRC-1 in uterus. This may have widespread effects on gene regulation. PMID:18174949

  7. Seven poor clusters of galaxies

    NASA Technical Reports Server (NTRS)

    Beers, T. C.; Geller, M. J.; Huchra, J. P.; Latham, D. W.; Davis, R. J.

    1984-01-01

    The measurement of 83 new redshifts from galaxies in the region of seven of the poor clusters of galaxies identified by Morgan et al (1975) and Albert et al (1977) has been followed by an estimation of cluster masses through the application of both the virial theorem and the projected mas method. For each system, these two estimates are consistent. For the two clusters with highest X-ray luminosities, the line-of-sight velocity dispersions are about 700 km/sec, while for the five other clusters, the dispersions are of the order of less than about 370 km/sec. The D or cD galaxy in each poor cluster is at the kinematic center of each system.

  8. Exposure assessment of trichloroethylene.

    PubMed Central

    Wu, C; Schaum, J

    2000-01-01

    This article reviews exposure information available for trichloroethylene (TCE) and assesses the magnitude of human exposure. The primary sources releasing TCE into the environment are metal cleaning and degreasing operations. Releases occur into all media but mostly into the air due to its volatility. It is also moderately soluble in water and can leach from soils into groundwater. TCE has commonly been found in ambient air, surface water, and groundwaters. The 1998 air levels in microg/m(3) across 115 monitors can be summarized as follows: range = 0.01-3.9, mean = 0.88. A California survey of large water utilities in 1984 found a median concentration of 3.0 microg/L. General population exposure to TCE occurs primarily by inhalation and water ingestion. Typical average daily intakes have been estimated as 11-33 microg/day for inhalation and 2-20 microg/day for ingestion. A small portion of the population is expected to have elevated exposures as a result of one or more of these pathways: inhalation exposures to workers involved in degreasing operations, ingestion and inhalation exposures occurring in homes with private wells located near disposal/contamination sites, and inhalation exposures to consumers using TCE products in areas of poor ventilation. More current and more extensive data on TCE levels in indoor air, water, and soil are needed to better characterize the distribution of background exposures in the general population and elevated exposures in special subpopulations. Images Figure 1 PMID:10807565

  9. Occludin expression in goldfish held in ion-poor water.

    PubMed

    Chasiotis, Helen; Effendi, Jennifer C; Kelly, Scott P

    2009-02-01

    With an emphasis on the tight junction protein occludin, the response of goldfish following abrupt exposure (0-120 h) as well as long-term acclimation (14 and 28 days) to ion-poor water (IPW) was examined. Both abrupt and long-term exposure to IPW lowered serum osmolality, [Na(+)] and [Cl(-)], and elevated serum glucose. After abrupt exposure to IPW, gill tissue exhibited a prompt and sustained decrease in Na(+)-K(+)-ATPase activity, and a transient increase in occludin expression that returned to control levels by 6 h. Following 14 and 28 days in IPW, gill occludin expression was markedly elevated, while Na(+)-K(+)-ATPase activity was only significantly different (elevated) at day 14. Kidney tissue exhibited an elevation in both Na(+)-K(+)-ATPase activity and occludin expression after 28 days; however, in the intestine, occludin expression declined at day 14 but did not differ from FW fish at day 28. These studies demonstrate that goldfish can tolerate abrupt as well as sustained exposure to ion-poor surroundings. Data also suggests that occludin may play an adaptive role in fishes acclimated to ion-poor conditions by contributing to the modulation of epithelial barrier properties in ionoregulatory tissues. PMID:18802707

  10. Aryl hydrocarbon receptor regulates CYP1B1 but not ABCB1 and ABCG2 in hCMEC/D3 human cerebral microvascular endothelial cells after TCDD exposure.

    PubMed

    Jacob, Aude; Potin, Sophie; Chapy, Hélène; Crete, Dominique; Glacial, Fabienne; Ganeshamoorthy, Kayathiri; Couraud, Pierre-Olivier; Scherrmann, Jean-Michel; Declèves, Xavier

    2015-07-10

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor activated by a variety of widespread persistent environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It can transactivate the expression of several target genes. Recently AhR transcripts were detected in isolated human brain microvessels and in the hCMEC/D3 human cerebral microvascular endothelial cell line, an in vitro model of the human cerebral endothelium. To date AhR implication in the co-regulation of ABCB1, ABCG2 and CYP1B1 at human cerebral endothelium has not been addressed. Here we investigated whether AhR could co-regulate ABCB1, ABCG2 and CYP1B1 expressions in the hCMEC/D3 cell line. Exposure to TCDD induced a concentration-dependent increase in CYP1B1 expression. We demonstrated AhR involvement in the TCDD-mediated increase in CYP1B1 expression by using small interfering RNA against AhR. Western blotting analysis also revealed an increase in CYP1B1 protein expression following TCDD exposure in hCMEC/D3. Regarding ABCB1 and ABCG2, exposure to TCDD had no effect on their protein expressions and functional activities. In conclusion our data indicated a differential modulation of CYP1B1 and ABCB1/ABCG2 expressions in hCMEC/D3 cells following TCDD exposure. PMID:25858487

  11. Do car-mounted mobile measurements used for radio-frequency spectrum regulation have an application for exposure assessments in epidemiological studies?

    PubMed

    Bolte, John F B; Maslanyj, Myron; Addison, Darren; Mee, Terry; Kamer, Jos; Colussi, Loek

    2016-01-01

    Knowing the spatial and temporal trends in environmental exposure to radiofrequency electromagnetic fields is important in studies investigating whether there are associated health effects on humans and ecological effects on plants and animals. The main objective of this study is to assess whether the RFeye car-mounted mobile measurement system used for radio frequency spectrum monitoring in The Netherlands and the United Kingdom could be of value in assessing exposure over large areas as an alternative to measuring exposure with personal exposure meters or using complex modelling techniques. We evaluated the responses of various body-worn personal exposure meters in comparison with the mobile measurement system for spectrum monitoring. The comparison was restricted to downlink mobile communication in the GSM900 and GSM1800 frequency bands. Repeated measurements were performed in three areas in Cambridge, United Kingdom and in three areas in Amersfoort, The Netherlands. We found that exposure assessments through the car-mounted measurements are at least of similar quality to exposure modelling and better than the body worn exposimeter data due to the absence of the shielding effect. The main conclusion is that the mobile measurements provide an efficient and low cost alternative particularly in mapping large areas. PMID:26540087

  12. Regulation of amino acid metabolism as a defensive strategy in the brain of three freshwater teleosts in response to high environmental ammonia exposure.

    PubMed

    Sinha, Amit Kumar; Giblen, Terri; AbdElgawad, Hamada; De Rop, Michelle; Asard, Han; Blust, Ronny; De Boeck, Gudrun

    2013-04-15

    Many teleosts have evolved mechanisms to cope with ammonia toxicity in the brain when confronted with high environmental ammonia (HEA). In the present study, the possible role of conversion of accumulated ammonia to glutamine and other free amino acids in the brain of three freshwater teleosts differing in their sensitivities to ammonia was investigated. The detoxification mode of ammonia in brain is suggested to be through amination of glutamate to glutamine by the coupled activities of glutamate dehydrogenase (GDH), transaminase (aspartate aminotransaminase 'AST' and alanine aminotransaminase 'ALT') and glutamine synthetase (GSase). We investigated the metabolic response of amino acids in the brain of highly sensitive salmonid Oncorhynchus mykiss (rainbow trout), the less sensitive cyprinid Cyprinus carpio (common carp) and the highly resistant cyprinid Carassius auratus (goldfish) when exposed to 1mM ammonia (as NH4HCO3; pH 7.9) for 0 h (control), 3 h, 12 h, 24 h, 48 h, 84 h and 180 h. Results show that HEA exposure increased ammonia accumulation significantly in the brain of all the three species from 12h onwards. Unlike in trout, ammonia accumulation in carp and goldfish was restored to control levels (48-84h); which was accompanied with a significant increase in glutamine content as well as GSase activity. In trout, glutamine levels also increased (84-180 h) but GSase was not activated. The elevated glutamine level in trout was accompanied by a significant depletion of the glutamate pool in contrast to the stable glutamate levels seen in carp and goldfish. This suggests a simultaneous increase in the rate of glutamate formation to match with the demand of glutamine formation in cyprinids. The activity of GDH was elevated significantly in carp and goldfish but remained unaltered in trout. Also, the transaminase enzymes (AST and ALT) were elevated significantly in exposed carp and goldfish while only ALT was up-regulated in trout. Consequently, in carp and

  13. Temptation in the background: non-consummatory exposure to food temptation enhances self-regulation in boys but not in girls

    PubMed Central

    Grubliauskiene, Aiste; Dewitte, Siegfried

    2014-01-01

    The abundance of calorie-dense low-nutrient food in everyday life raises the question as to how children deal with such opportunities. We investigate whether pre-exposure to the object of temptation in a situation that discourages consumption boosts children’s ability to resist similar temptation subsequently. We show that 7–12-year-old boys, but not girls, demonstrate increased resistance to a temptation after pre-exposure to a similar temptation. Future research might explore the role of exposure to temptation in girls. PMID:25101042

  14. Livestock services and the poor.

    PubMed

    Ahuja, V; Redmond, E

    2004-04-01

    This paper reviews the economic framework for the delivery of livestock services to the poor. It is argued that the demand for livestock products is likely to increase rapidly and the ability of the poor to participate in the opportunities presented by this growth is linked critically to the availability of good service support, both on the input and output side. Governments therefore have a responsibility to supply the necessary public goods (including the institutions and legal frameworks), and the market infrastructure for facilitating the emergence of efficient markets for livestock services. The paper further argues that the dynamics of public policy in developing countries are much more complex than the simple application of economic logic. It is the larger political economy that often dictates policy choices. It is therefore important to integrate political economy and governance issues into the economic debate on livestock service delivery. The paper also reviews the context in which the markets for livestock services will need to function. Different countries are facing very different sets of issues, and the identification of possible interventions in livestock service markets would require careful field research and analysis. In this context, the paper suggests the elements of a research agenda for the next few years. PMID:15080541

  15. Seven poor clusters of galaxies

    NASA Astrophysics Data System (ADS)

    Beers, T. C.; Geller, M. J.; Huchra, J. P.; Latham, D. W.; Davis, R. J.

    1984-08-01

    The authors have measured 83 new redshifts for galaxies in the region of seven of the poor clusters of galaxies identified by Morgan, Kayser, and White and Albert, White, and Morgan. For three systems (MKW 1s, AWM 1, and AWM 7) complete redshift samples were obtained for galaxies brighter than mB(0) = 15.7 within 1° of the D or cD galaxy. The authors estimate masses for the clusters by applying both the virial theorem and the projected mass method. For the two clusters with the highest X-ray luminosities, the line-of-sight velocity dispersions are ≡700 km s-1, and mass-to-light ratios M/LB(0) ⪆ 400 M_sun;/L_sun;. For the five other clusters the velocity dispersions are ⪉370 km s-1, and four of the five have mass-to-light ratios ⪉250 M_sun;/L_sun;. The D or cD galaxy in each poor cluster is at the kinematic center of the system.

  16. Adult and paediatric poor metabolisers of desloratadine: an assessment of pharmacokinetics and safety.

    PubMed

    Prenner, Bruce; Kim, Kenneth; Gupta, Samir; Khalilieh, Sauzanne; Kantesaria, Bhavna; Manitpisitkul, Prasarn; Lorber, Richard; Wang, Zaiqi; Lutsky, Barry

    2006-03-01

    Antihistamines are widely used to treat allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) in adults and children. Desloratadine is a once-daily oral antihistamine with a favourable sedation profile that is approved for the treatment of AR and CIU. Phenotypic polymorphism in the metabolism of desloratadine has been observed, such that some individuals have a decreased ability to form 3-hydroxydesloratadine, the major metabolite of desloratadine; such individuals are termed 'poor metabolisers of desloratadine'. This review describes the prevalence of poor metabolisers of desloratadine, quantifies the exposure to desloratadine in poor metabolisers and demonstrates that the increased exposure in poor metabolisers is independent of age when administered at age-appropriate doses. Furthermore, this review demonstrates that the increased exposure to desloratadine in poor metabolisers is not associated with any changes in the safety and tolerability profile of desloratadine, including cardiovascular safety. PMID:16503743

  17. Child Health: Reaching the Poor

    PubMed Central

    Wagstaff, Adam; Bustreo, Flavia; Bryce, Jennifer; Claeson, Mariam

    2004-01-01

    In most countries, rates of mortality and malnutrition among children continue to decline, but large inequalities between poor and better-off children exist, both between and within countries. These inequalities, which appear to be widening, call into question the strategies for child mortality reduction relied upon to date. We review (1) what is known about the causes of socioeconomic inequalities in child health and where programs aimed at reducing inequalities may be most effectively focused and (2) what is known about the success of actual programs in narrowing these inequalities. We end with lessons learned: the need for better evidence, but most of all for a new approach to improving the health of all children that is evidence based, broad, and multifaceted. PMID:15117689

  18. Serving the world's poor, profitably.

    PubMed

    Prahalad, C K; Hammond, Allen

    2002-09-01

    By stimulating commerce and development at the bottom of the economic pyramid, multi-nationals could radically improve the lives of billions of people and help create a more stable, less dangerous world. Achieving this goal does not require MNCs to spearhead global social-development initiatives for charitable purposes. They need only act in their own self-interest. How? The authors lay out the business case for entering the world's poorest markets. Fully 65% of the world's population earns less than $2,000 per year--that's 4 billion people. But despite the vastness of this market, it remains largely untapped. The reluctance to invest is easy to understand, but it is, by and large, based on outdated assumptions of the developing world. While individual incomes may be low, the aggregate buying power of poor communities is actually quite large, representing a substantial market in many countries for what some might consider luxury goods like satellite television and phone services. Prices, and margins, are often much higher in poor neighborhoods than in their middle-class counterparts. And new technologies are already steadily reducing the effects of corruption, illiteracy, inadequate infrastructure, and other such barriers. Because these markets are in the earliest stages of economic development, revenue growth for multi-nationals entering them can be extremely rapid. MNCs can also lower costs, not only through low-cost labor but by transferring operating efficiencies and innovations developed to serve their existing operations. Certainly, succeeding in such markets requires MNCs to think creatively. The biggest change, though, has to come from executives: Unless business leaders confront their own preconceptions--particularly about the value of high-volume, low-margin businesses--companies are unlikely to master the challenges or reap the rewards of these developing markets. PMID:12227146

  19. Altered Expression of Genes in Signaling Pathways Regulating Proliferation of Hematopoietic Stem and Progenitor Cells in Mice with Subchronic Benzene Exposure.

    PubMed

    Sun, Rongli; Zhang, Juan; Xiong, Mengzhen; Wei, Haiyan; Tan, Kehong; Yin, Lihong; Pu, Yuepu

    2015-08-01

    Leukemias and hematopoietic disorders induced by benzene may arise from the toxicity of benzene to hematopoietic stem or progenitor cells (HS/PCs). Since there is a latency period between initial benzene exposure and the development of leukemia, subsequent impact of benzene on HS/PCs are crucial for a deeper understanding of the carcinogenicity and hematotoxicity in post-exposure stage. This study aims to explore the effects of benzene on HS/PCs and gene-expression in Wnt, Notch and Hh signaling pathways in post-exposure stage. The C3H/He mice were injected subcutaneously with benzene (0, 150, 300 mg/kg/day) for three months and were monitored for another 10 months post-exposure. The body weights were monitored, the relative organ weights, blood parameters and bone marrow smears were examined. Frequency of lineage(-) sca-1(+) c-kit(+) (LSK) cells, capability of colony forming and expression of genes in Wnt, Notch and Hedghog (Hh) signaling pathways were also analyzed. The colony formation of the progenitor cells for BFU-E, CFU-GEMM and CFU-GM was significantly decreased with increasing benzene exposure relative to controls, while no significant difference was observed in colonies for CFU-G and CFU-M. The mRNA level of cyclin D1 was increased and Notch 1 and p53 were decreased in LSK cells in mice exposed to benzene but with no statistical significance. These results suggest that subsequent toxic effects of benzene on LSK cells and gene expression in Wnt, Notch and Hh signaling pathways persist in post-exposure stage and may play roles in benzene-induced hematotoxicity. PMID:26262635

  20. Poorly soluble particulates: searching for a unifying denominator of nanoparticles and fine particles for DNEL estimation.

    PubMed

    Pauluhn, Jürgen

    2011-01-11

    Under the new European chemicals regulation, REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) a Derived No-Effect Level (DNEL), i.e., the level of exposure above which humans should not be exposed, is defined. The focus of this paper is to develop a weight-of-evidence-based DNEL-approach for inhaled poorly soluble particles. Despite the common mode of action of inhaled insoluble, spherical particulate matter (PM), a unifying, most appropriate metric conferring pulmonary biopersistence and toxicity has yet not been demonstrated. Nonetheless, there is compelling evidence from repeated rat inhalation exposure studies suggesting that the particle displacement volume is the most prominent unifying denominator linking the pulmonary retained dose with toxicity. Procedures were developed to analyze and model the pulmonary toxicokinetics from short-term to long-term exposure. Six different types of poorly soluble nano- to submicron PMs were compared: ultrafine and pigmentary TiO₂, synthetic iron oxide (Fe₃O₄, magnetite), two aluminum oxyhydroxides (AlOOH, Boehmite) with primary isometric particles approximately of either 10 or 40 nm, and MWCNT. The specific agglomerate densities of these materials ranged from 0.1 g/cm³ (MWCNT) to 5 g/cm³ (Fe₃O₄). Along with all PM, due to their long retention half-times and associated biopersistence in the lung, even short-term inhalation studies may require postexposure periods of at least 3 months to reveal PM-specific dispositional and toxicological characteristics. This analysis provides strong evidence that pulmonary toxicity (sustained inflammation) is dependent on the volume-based cumulative lung exposure dose. Lung toxicity, evidenced by PMN in BAL occurred at lung doses exceeding 10-times the overload threshold. Furthermore, the conclusion is supported that repeated inhalation studies on rats should utilize an experimental window of cumulative volume loads of respirable PM in the range of 1

  1. Body temperature regulation in diabetes.

    PubMed

    Kenny, Glen P; Sigal, Ronald J; McGinn, Ryan

    2016-01-01

    The effects of type 1 and type 2 diabetes on the body's physiological response to thermal stress is a relatively new topic in research. Diabetes tends to place individuals at greater risk for heat-related illness during heat waves and physical activity due to an impaired capacity to dissipate heat. Specifically, individuals with diabetes have been reported to have lower skin blood flow and sweating responses during heat exposure and this can have important consequences on cardiovascular regulation and glycemic control. Those who are particularly vulnerable include individuals with poor glycemic control and who are affected by diabetes-related complications. On the other hand, good glycemic control and maintenance of aerobic fitness can often delay the diabetes-related complications and possibly the impairments in heat loss. Despite this, it is alarming to note the lack of information regarding diabetes and heat stress given the vulnerability of this population. In contrast, few studies have examined the effects of cold exposure on individuals with diabetes with the exception of its therapeutic potential, particularly for type 2 diabetes. This review summarizes the current state of knowledge regarding the impact of diabetes on heat and cold exposure with respect to the core temperature regulation, cardiovascular adjustments and glycemic control while also considering the beneficial effects of maintaining aerobic fitness. PMID:27227101

  2. Body temperature regulation in diabetes

    PubMed Central

    Kenny, Glen P.; Sigal, Ronald J.; McGinn, Ryan

    2016-01-01

    ABSTRACT The effects of type 1 and type 2 diabetes on the body's physiological response to thermal stress is a relatively new topic in research. Diabetes tends to place individuals at greater risk for heat-related illness during heat waves and physical activity due to an impaired capacity to dissipate heat. Specifically, individuals with diabetes have been reported to have lower skin blood flow and sweating responses during heat exposure and this can have important consequences on cardiovascular regulation and glycemic control. Those who are particularly vulnerable include individuals with poor glycemic control and who are affected by diabetes-related complications. On the other hand, good glycemic control and maintenance of aerobic fitness can often delay the diabetes-related complications and possibly the impairments in heat loss. Despite this, it is alarming to note the lack of information regarding diabetes and heat stress given the vulnerability of this population. In contrast, few studies have examined the effects of cold exposure on individuals with diabetes with the exception of its therapeutic potential, particularly for type 2 diabetes. This review summarizes the current state of knowledge regarding the impact of diabetes on heat and cold exposure with respect to the core temperature regulation, cardiovascular adjustments and glycemic control while also considering the beneficial effects of maintaining aerobic fitness. PMID:27227101

  3. Transcriptional response of stress-regulated genes to cadmium exposure in the cockle Cerastoderma glaucum from the gulf of Gabès area (Tunisia).

    PubMed

    Karray, Sahar; Marchand, Justine; Moreau, Brigitte; Tastard, Emmanuelle; Thiriet-Rupert, Stanislas; Geffard, Alain; Delahaut, Laurence; Denis, Françoise; Hamza-Chaffai, Amel; Chénais, Benoît

    2015-11-01

    This study investigates cadmium effects on key messenger RNA (mRNA) expression (MT, MnSOD, CuZnSOD, CAT, ABCB1, HSP70, and CO1) by qPCR in the cockle Cerastoderma glaucum after chronic exposure to two high but environmentally relevant concentrations of CdCl2 (50 μg/L and 5 mg/L) for 12 h to 18 days. Cd accumulation measured in cockles' tissues is significantly higher in both treatment conditions compared to controls and in a dose-dependent manner. Stress on stress tests performed at different times of the experiment clearly demonstrated that exposure to both concentrations of Cd significantly affects cockle survival time in air. Important changes in gene transcription were also highlighted. In particular, MT, HSP70, CAT, and CuZnSOD seem to be relevant biomarkers of Cd exposure because (1) their mRNA levels increase upon exposure and (2) they are highly correlated to Cd accumulation in tissues. Results may be useful for control strategies and for the use of cockles as sentinel organisms. PMID:25523290

  4. Acrolein Exposure Blocks Down-Regulation of Cytokines and IgE Antibody in a Mucosal Tolerance Model but does not Alter Phenotypic Markers of Allergic Lung Disease

    EPA Science Inventory

    Acrolein (ACR) is a highly reactive upper airway toxicant that humans are exposed in a variety of environmental situations. Here we examined the effect of ACR exposure on development of immune tolerance in mice. To induce tolerance, female BALB/C mice were intranasally inoculate...

  5. Violence Exposure and Adjustment in Inner-City Youth: Child and Caregiver Emotion Regulation Skill, Caregiver?Child Relationship Quality, and Neighborhood Cohesion as Protective Factor

    ERIC Educational Resources Information Center

    Kliewer, Wendy; Cunningham, Jera Nelson; Diehl, Robyn; Parrish, Katie Adams; Walker, Jean M.; Atiyeh, Cynthia; Neace, Brooke; Duncan, Larissa; Taylor, Kelli; Mejia, Roberto

    2004-01-01

    This short-term, longitudinal interview study used an ecological framework to explore protective factors within the child, the caregiver, the caregiver?child relationship, and the community that might moderate relations between community violence exposure and subsequent internalizing and externalizing adjustment problems and the different patterns…

  6. Occupational solvent exposure and cognition

    PubMed Central

    Sabbath, E.L.; Glymour, M.M.; Berr, C.; Singh-Manoux, A.; Zins, M.; Goldberg, M.

    2012-01-01

    Objective: Chronic occupational solvent exposure is associated with long-term cognitive deficits. Cognitive reserve may protect solvent-exposed workers from cognitive impairment. We tested whether the association between chronic solvent exposure and cognition varied by educational attainment, a proxy for cognitive reserve. Methods: Data were drawn from a prospective cohort of French national gas and electricity (GAZEL) employees (n = 4,134). Lifetime exposure to 4 solvent types (chlorinated solvents, petroleum solvents, benzene, and nonbenzene aromatic solvents) was assessed using a validated job-exposure matrix. Education was dichotomized at less than secondary school or below. Cognitive impairment was defined as scoring below the 25th percentile on the Digit Symbol Substitution Test at mean age 59 (SD 2.8; 88% of participants were retired at testing). Log-binomial regression was used to model risk ratios (RRs) for poor cognition as predicted by solvent exposure, stratified by education and adjusted for sociodemographic and behavioral factors. Results: Solvent exposure rates were higher among less-educated patients. Within this group, there was a dose-response relationship between lifetime exposure to each solvent type and RR for poor cognition (e.g., for high exposure to benzene, RR = 1.24, 95% confidence interval 1.09–1.41), with significant linear trends (p < 0.05) in 3 out of 4 solvent types. Recency of solvent exposure also predicted worse cognition among less-educated patients. Among those with secondary education or higher, there was no significant or near-significant relationship between any quantification of solvent exposure and cognition. Conclusions: Solvent exposure is associated with poor cognition only among less-educated individuals. Higher cognitive reserve in the more-educated group may explain this finding. PMID:22641403

  7. 12 CFR 206.4 - Credit exposure.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 2 2011-01-01 2011-01-01 false Credit exposure. 206.4 Section 206.4 Banks and... LIABILITIES (REGULATION F) § 206.4 Credit exposure. (a) Limits on credit exposure. (1) The policies and... credit exposure to an individual correspondent to not more than 25 percent of the bank's total...

  8. 12 CFR 206.4 - Credit exposure.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 2 2013-01-01 2013-01-01 false Credit exposure. 206.4 Section 206.4 Banks and... LIABILITIES (REGULATION F) § 206.4 Credit exposure. (a) Limits on credit exposure. (1) The policies and... credit exposure to an individual correspondent to not more than 25 percent of the bank's total...

  9. 12 CFR 206.4 - Credit exposure.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 2 2012-01-01 2012-01-01 false Credit exposure. 206.4 Section 206.4 Banks and... LIABILITIES (REGULATION F) § 206.4 Credit exposure. (a) Limits on credit exposure. (1) The policies and... credit exposure to an individual correspondent to not more than 25 percent of the bank's total...

  10. 12 CFR 206.4 - Credit exposure.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Credit exposure. 206.4 Section 206.4 Banks and... LIABILITIES (REGULATION F) § 206.4 Credit exposure. (a) Limits on credit exposure. (1) The policies and... credit exposure to an individual correspondent to not more than 25 percent of the bank's total...

  11. Military Exposures

    MedlinePlus

    ... Index Agent Orange Agent Orange Home Facts about Herbicides Veterans' Diseases Birth Defects Benefits Exposure Locations Provider ... for Providers Diagnosis and Treatment of Exposure Health Effects More Provider Resources » return to top Get Email ...

  12. How much more exposed are the poor to natural disasters? Global and regional measurement.

    PubMed

    Kim, Namsuk

    2012-04-01

    This paper proposes a simple indicator to measure the exposure to natural disasters for the poor and non-poor population, in order to assess the global and regional trend of natural hazard and poverty. Globally, poor people are two times more exposed to natural disasters than the non-poor in the twenty-first century. The time trend varies across regions, with poor people in East Asia and Pacific being most exposed to natural disasters, followed by those in South Asia and Sub-Saharan Africa. The change of exposure measure over time is decomposed into two factors: a pure exposure change, which could be fuelled by climate change; and a concentration component. The result shows that the total net increase of exposure between the 1970s and the 2000s is driven significantly by the increased concentration of the poor (26 per cent) in disaster-prone areas, whereas the contribution of that factor remains very small for the non-poor (six per cent). PMID:21995667

  13. Early-life lead exposure results in dose- and sex-specific effects on weight and epigenetic gene regulation in weanling mice

    PubMed Central

    Faulk, Christopher; Barks, Amanda; Liu, Kevin; Goodrich, Jaclyn M; Dolinoy, Dana C

    2013-01-01

    Aims Epidemiological and animal data suggest that the development of adult chronic conditions is influenced by early-life exposure-induced changes to the epigenome. This study investigates the effects of perinatal lead (Pb) exposure on DNA methylation and bodyweight in weanling mice. Materials & methods Viable yellow agouti (Avy) mouse dams were exposed to 0, 2.1, 16 and 32 ppm Pb acetate before conception through weaning. Epigenetic effects were evaluated by scoring coat color of Avy/a offspring and quantitative bisulfite sequencing of two retrotransposon-driven (Avy and CDK5 activator-binding protein intracisternal A particle element) and two imprinted (Igf2 and Igf2r) loci in tail DNA. Results Maternal blood Pb levels were below the limit of detection in controls, and 4.1, 25.1 and 32.1 μg/dl for each dose, respectively. Pb exposure was associated with a trend of increased wean bodyweight in males (p = 0.03) and altered coat color in Avy/a offspring. DNA methylation at Avy and the CDK5 activator-binding protein intracisternal A-particle element was significantly different from controls following a cubic trend (p = 0.04; p = 0.01), with male-specific effects at the Avy locus. Imprinted genes did not shift in methylation across exposures. Conclusion Dose- and sex-specific responses in bodyweight and DNA methylation indicate that Pb acts on the epigenome in a locus-specific fashion, dependent on the genomic feature hosting the CpG site of interest, and that sex is a factor in epigenetic response. PMID:24059796

  14. Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2

    PubMed Central

    Hu, Yan; Zhao, Weilu; Zuo, Zhiyi; Yu, Qi; Liu, Zhiyi; Lin, Jiamei; Feng, Yunlin; Li, Binda; Wu, Liuqin; Xu, Lin

    2016-01-01

    Increasing evidence indicates that most general anesthetics can harm developing neurons and induce cognitive dysfunction in a dose- and time-dependent manner. Histone deacetylase 2 (HDAC2) has been implicated in synaptic plasticity and learning and memory. Our previous results showed that maternal exposure to general anesthetics during late pregnancy impaired the offspring’s learning and memory, but the role of HDAC2 in it is not known yet. In the present study, pregnant rats were exposed to 1.5% isoflurane in 100% oxygen for 2, 4 or 8 hours or to 100% oxygen only for 8 hours on gestation day 18 (E18). The offspring born to each rat were randomly subdivided into 2 subgroups. Thirty days after birth, the Morris water maze (MWM) was used to assess learning and memory in the offspring. Two hours before each MWM trial, an HDAC inhibitor (SAHA) was given to the offspring in one subgroup, whereas a control solvent was given to those in the other subgroup. The results showed that maternal exposure to isoflurane impaired learning and memory of the offspring, impaired the structure of the hippocampus, increased HDAC2 mRNA and downregulated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) mRNA, N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and NR2B protein in the hippocampus. These changes were proportional to the duration of the maternal exposure to isoflurane and were reversed by SAHA. These results suggest that exposure to isoflurane during late pregnancy can damage the learning and memory of the offspring rats via the HDAC2-CREB -NR2B pathway. This effect can be reversed by HDAC2 inhibition. PMID:27536989

  15. Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2.

    PubMed

    Luo, Foquan; Hu, Yan; Zhao, Weilu; Zuo, Zhiyi; Yu, Qi; Liu, Zhiyi; Lin, Jiamei; Feng, Yunlin; Li, Binda; Wu, Liuqin; Xu, Lin

    2016-01-01

    Increasing evidence indicates that most general anesthetics can harm developing neurons and induce cognitive dysfunction in a dose- and time-dependent manner. Histone deacetylase 2 (HDAC2) has been implicated in synaptic plasticity and learning and memory. Our previous results showed that maternal exposure to general anesthetics during late pregnancy impaired the offspring's learning and memory, but the role of HDAC2 in it is not known yet. In the present study, pregnant rats were exposed to 1.5% isoflurane in 100% oxygen for 2, 4 or 8 hours or to 100% oxygen only for 8 hours on gestation day 18 (E18). The offspring born to each rat were randomly subdivided into 2 subgroups. Thirty days after birth, the Morris water maze (MWM) was used to assess learning and memory in the offspring. Two hours before each MWM trial, an HDAC inhibitor (SAHA) was given to the offspring in one subgroup, whereas a control solvent was given to those in the other subgroup. The results showed that maternal exposure to isoflurane impaired learning and memory of the offspring, impaired the structure of the hippocampus, increased HDAC2 mRNA and downregulated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) mRNA, N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and NR2B protein in the hippocampus. These changes were proportional to the duration of the maternal exposure to isoflurane and were reversed by SAHA. These results suggest that exposure to isoflurane during late pregnancy can damage the learning and memory of the offspring rats via the HDAC2-CREB -NR2B pathway. This effect can be reversed by HDAC2 inhibition. PMID:27536989

  16. Hexabromocyclododecane exposure induces cardiac hypertrophy and arrhythmia by inhibiting miR-1 expression via up-regulation of the homeobox gene Nkx2.5.

    PubMed

    Wu, Meifang; Wu, Di; Wang, Chonggang; Guo, Zhizhun; Li, Bowen; Zuo, Zhenghong

    2016-01-25

    Hexabromocyclododecane (HBCD) is one of the most widely used brominated flame retardants. Although studies have reported that HBCD can cause a wide range of toxic effects on animals including humans, limited information can be found about its cardiac toxicity. In the present study, zebrafish embryos were exposed to HBCD at low concentrations of 0, 2, 20 and 200 nM. The results showed that HBCD exposure could induce cardiac hypertrophy and increased deposition of collagen. In addition, disordered calcium (Ca(2+)) handling was observed in H9C2 rat cardiomyocyte cells exposed to HBCD. Using small RNA sequencing and real-time quantitative PCR, HBCD exposure was shown to induce significant changes in the miRNA expression profile associated with the cardiovascular system. Further findings indicated that miR-1, which was depressed by Nkx2.5, might play a fundamental role in mediating cardiac hypertrophy and arrhythmia via its target genes Mef2a and Irx5 after HBCD treatment. HBCD exposure induced an arrhythmogenic disorder, which was triggered by the imbalance of Ryr2, Serca2a and Ncx1 expression, inducing Ca(2+) overload in the sarcoplasmic reticulum and high Ca(2+)-ATPase activities in the H9C2 cells. PMID:26476318

  17. Asbestos Exposure Assessment Database

    NASA Technical Reports Server (NTRS)

    Arcot, Divya K.

    2010-01-01

    Exposure to particular hazardous materials in a work environment is dangerous to the employees who work directly with or around the materials as well as those who come in contact with them indirectly. In order to maintain a national standard for safe working environments and protect worker health, the Occupational Safety and Health Administration (OSHA) has set forth numerous precautionary regulations. NASA has been proactive in adhering to these regulations by implementing standards which are often stricter than regulation limits and administering frequent health risk assessments. The primary objective of this project is to create the infrastructure for an Asbestos Exposure Assessment Database specific to NASA Johnson Space Center (JSC) which will compile all of the exposure assessment data into a well-organized, navigable format. The data includes Sample Types, Samples Durations, Crafts of those from whom samples were collected, Job Performance Requirements (JPR) numbers, Phased Contrast Microscopy (PCM) and Transmission Electron Microscopy (TEM) results and qualifiers, Personal Protective Equipment (PPE), and names of industrial hygienists who performed the monitoring. This database will allow NASA to provide OSHA with specific information demonstrating that JSC s work procedures are protective enough to minimize the risk of future disease from the exposures. The data has been collected by the NASA contractors Computer Sciences Corporation (CSC) and Wyle Laboratories. The personal exposure samples were collected from devices worn by laborers working at JSC and by building occupants located in asbestos-containing buildings.

  18. Cocaine exposure prior to pregnancy alters the psychomotor response to cocaine and transcriptional regulation of the dopamine D1 receptor in adult male offspring.

    PubMed

    Sasaki, Aya; Constantinof, Andrea; Pan, Pauline; Kupferschmidt, Dave A; McGowan, Patrick O; Erb, Suzanne

    2014-05-15

    There is evidence that maternal experience prior to pregnancy can play an important role in behavioral, physiological, and genetic programming of offspring. Likewise, exposure to cocaine in utero can result in marked changes in central nervous system function of offspring. In this study, we examined whether exposure of rat dams to cocaine prior to pregnancy subsequently alters indices of behavior, physiology, and gene expression in offspring. Multiple outcome measures were examined in adult male offspring: (1) behavioral expression of cocaine-induced psychomotor activation; (2) levels of corticosterone in response to immobilization stress; and (3) expression of multiple genes, including dopamine receptor D1 (DRD1) and D2 (DRD2), glucocorticoid receptor (GR), and corticotropin-releasing factor (CRF), in functionally relevant brain regions. Adult Sprague-Dawley females were exposed to cocaine (15-30 mg/kg, i.p.) or saline for 10 days, and were then mated to drug naïve males of the same strain. Separate groups of adult male offspring were tested for their acute psychomotor response to cocaine (0, 15, 30 mg/kg, i.p.), corticosterone responsivity to 20 min of immobilization stress, and expression of multiple genes using quantitative PCR. Offspring of dams exposed to cocaine prior to conception exhibited increased psychomotor sensitivity to cocaine, and upregulated gene expression of DRD1 in the medial prefrontal cortex (mPFC). Neither stress-induced corticosterone levels nor gene expression of GR or CRF genes were altered. These data suggest that cocaine exposure before pregnancy can serve to enhance psychomotor sensitivity to cocaine in offspring, possibly via alterations in dopamine function that include upregulation of the DRD1. PMID:24583058

  19. Exposure to2,2',4,4'-tetrabromodiphenyl ether (BDE-47) alters thyroid hormone levels and thyroid hormone-regulated gene transcription in manila clam Ruditapes philippinarum.

    PubMed

    Song, Ying; Miao, Jingjing; Pan, Luqing; Wang, Xin

    2016-06-01

    Polybrominated diphenyl ethers (PBDEs) have the potential to disturb the thyroid endocrine system in vertebrates, but little is known about the disruptive effects of PBDEs on marine bivalves. In this study, we first examined the effects of BDE-47 exposure on growth of juvenile manila clams Ruditapes philippinarum. The result showed that 1.0 and 10 μg L(-1) BDE-47 had adverse effects on 14-d shell-length growth of juvenile clams. Then, one-year-old adult clams were exposed to 0, 0.1 and 1 μg L(-1) BDE-47 for 15 d. BDE-47 (1 μg L(-1)) exposure caused significant decreases of total T4 (thyroxine) by 40% and T3 (3,5,3'-triiodothyronine) by 75% concentrations in haemolymph of the clams. Transcription of genes involved in thyroid hormone synthesis and metabolism were also studied by quantitative RT-PCR. Gene expression levels of sodium iodide symporter (rp-NIS), iodothyronine deiodinase (rp-Deio) and thyroid peroxidase (rp-TPO) were increased in a dose-dependent manner at day 5 and day 10, while monocarboxylate transporter 8 (rp-Mct8) was downregulated at day 5, day 10 and day 15. The effect and preliminary mechanism observed in the present study were consistent with the results from previous studies on rodent and fish, implying that exposure to BDE-47 may pose threat to thyroid hormone homeostasis in bivalves through thyroid synthesis and metabolism pathways. This study may provide a first step towards understanding of the thyroid function disruptive effects of PBDEs on marine bivalves and the underlying mechanism across taxonomic groups and phyla. PMID:26943874

  20. Moderate Alcohol Exposure during the Rat Equivalent to the Third Trimester of Human Pregnancy Alters Regulation of GABAA Receptor-Mediated Synaptic Transmission by Dopamine in the Basolateral Amygdala.

    PubMed

    Diaz, Marvin Rafael; Jotty, Karick; Locke, Jason L; Jones, Sara R; Valenzuela, Carlos Fernando

    2014-01-01

    Fetal ethanol (EtOH) exposure leads to a range of neurobehavioral alterations, including deficits in emotional processing. The basolateral amygdala (BLA) plays a critical role in modulating emotional processing, in part, via dopamine (DA) regulation of GABA transmission. This BLA modulatory system is acquired during the first 2 weeks of postnatal life in rodents (equivalent to the third trimester of human pregnancy) and we hypothesized that it could be altered by EtOH exposure during this period. We found that exposure of rats to moderate levels of EtOH vapor during the third trimester-equivalent [postnatal days (P) 2-12] alters DA modulation of GABAergic transmission in BLA pyramidal neurons during periadolescence. Specifically, D1R-mediated potentiation of spontaneous inhibitory postsynaptic currents (IPSCs) was significantly attenuated in EtOH-exposed animals. However, this was associated with a compensatory decrease in D3R-mediated suppression of miniature IPSCs. Western blot analysis revealed that these effects were not a result of altered D1R or D3R levels. BLA samples from EtOH-exposed animals also had significantly lower levels of the DA precursor (L-3,4-dihydroxyphenylalanine) but DA levels were not affected. This is likely a consequence of reduced catabolism of DA, as indicated by reduced levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid in the BLA samples. Anxiety-like behavior was not altered in EtOH-exposed animals. This is the first study to demonstrate that the modulatory actions of DA in the BLA are altered by developmental EtOH exposure. Although compensatory adaptations were engaged in our moderate EtOH exposure paradigm, it is possible that these are not able to restore homeostasis and correct anxiety-like behaviors under conditions of heavier EtOH exposure. Therefore, future studies should investigate the potential role of alterations in the modulatory actions of DA in the pathophysiology of fetal alcohol spectrum disorders. PMID

  1. Personal Exposure Monitoring Wearing Protocol Compliance: An Initial Assessment of Quantitative Measurements

    EPA Science Inventory

    Personal exposure sampling provides the most accurate and representative assessment of exposure to a pollutant, but only if measures are implemented to minimize exposure misclassification and reduce confounders that may cause misinterpretation of the collected data. Poor complian...

  2. Do Middle-Class Students Perceive Poor Women and Poor Men Differently?

    ERIC Educational Resources Information Center

    Cozzarelli, Catherine; Tagler, Michael J.; Wilkinson, Anna V.

    2002-01-01

    Examined college students' attitudes and stereotypes regarding poor women, attributions for their poverty, and whether those thoughts and feelings differed from those about poor men. Attitudes and stereotypes were significantly more positive regarding poor women than poor men. Participants endorsed internal attributions for both women's and men's…

  3. Controlled bile acid exposure to oesophageal mucosa causes up-regulation of nuclear γ-H2AX possibly via iNOS induction

    PubMed Central

    Jiang, Bo; Zhao, Shengqian; Tao, Zhen; Wen, Jin; Yang, Yancheng; Zheng, Yin; Yan, Hongling; Sheng, Ying; Gao, Aimin

    2016-01-01

    Using an in vitro model in which flatmounts of oesophagus was periodically exposed to bile acids, we demonstrate, using multiple methods, that the bile acid receptor TGR5, inducible nitric oxide synthase (iNOS) and γ-histone family 2A variant (γ-H2AX) are up-regulated. This indicates that bile acids cause up-regulation of iNOS, which further causes genotoxic stress as evidenced by increase of the highly sensitive marker, phosphorylated histone. In vitro nitric oxide (NO) assays showed increased production of nitric acid in the oesophageal epithelium exposed to the bile acids. This increase was inhibited in the presence of the nonspecific iNOS inhibitor aminoguanidine (AG). Cumulatively, the results of the present study provide suggestion that not only acid reflux, but also non-acid reflux of bile may cause genotoxic stress. These aspects merit to be tested in wide spectrum of Barrett epithelial tissues. PMID:27247425

  4. Controlled bile acid exposure to oesophageal mucosa causes up-regulation of nuclear γ-H2AX possibly via iNOS induction.

    PubMed

    Jiang, Bo; Zhao, Shengqian; Tao, Zhen; Wen, Jin; Yang, Yancheng; Zheng, Yin; Yan, Hongling; Sheng, Ying; Gao, Aimin

    2016-08-01

    Using an in vitro model in which flatmounts of oesophagus was periodically exposed to bile acids, we demonstrate, using multiple methods, that the bile acid receptor TGR5, inducible nitric oxide synthase (iNOS) and γ-histone family 2A variant (γ-H2AX) are up-regulated. This indicates that bile acids cause up-regulation of iNOS, which further causes genotoxic stress as evidenced by increase of the highly sensitive marker, phosphorylated histone. In vitro nitric oxide (NO) assays showed increased production of nitric acid in the oesophageal epithelium exposed to the bile acids. This increase was inhibited in the presence of the nonspecific iNOS inhibitor aminoguanidine (AG). Cumulatively, the results of the present study provide suggestion that not only acid reflux, but also non-acid reflux of bile may cause genotoxic stress. These aspects merit to be tested in wide spectrum of Barrett epithelial tissues. PMID:27247425

  5. Exposure to 9,10-phenanthrenequinone accelerates malignant progression of lung cancer cells through up-regulation of aldo-keto reductase 1B10

    SciTech Connect

    Matsunaga, Toshiyuki; Morikawa, Yoshifumi; Haga, Mariko; Endo, Satoshi; Soda, Midori; Yamamura, Keiko; El-Kabbani, Ossama; Tajima, Kazuo; Ikari, Akira; Hara, Akira

    2014-07-15

    Inhalation of 9,10-phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust, exerts fatal damage against a variety of cells involved in respiratory function. Here, we show that treatment with high concentrations of 9,10-PQ evokes apoptosis of lung cancer A549 cells through production of reactive oxygen species (ROS). In contrast, 9,10-PQ at its concentrations of 2 and 5 μM elevated the potentials for proliferation, invasion, metastasis and tumorigenesis, all of which were almost completely inhibited by addition of an antioxidant N-acetyl-L-cysteine, inferring a crucial role of ROS in the overgrowth and malignant progression of lung cancer cells. Comparison of mRNA expression levels of six aldo-keto reductases (AKRs) in the 9,10-PQ-treated cells advocated up-regulation of AKR1B10 as a major cause contributing to the lung cancer malignancy. In support of this, the elevation of invasive, metastatic and tumorigenic activities in the 9,10-PQ-treated cells was significantly abolished by the addition of a selective AKR1B10 inhibitor oleanolic acid. Intriguingly, zymographic and real-time PCR analyses revealed remarkable increases in secretion and expression, respectively, of matrix metalloproteinase 2 during the 9,10-PQ treatment, and suggested that the AKR1B10 up-regulation and resultant activation of mitogen-activated protein kinase cascade are predominant mechanisms underlying the metalloproteinase induction. In addition, HPLC analysis and cytochrome c reduction assay in in vitro 9,10-PQ reduction by AKR1B10 demonstrated that the enzyme catalyzes redox-cycling of this quinone, by which ROS are produced. Collectively, these results suggest that AKR1B10 is a key regulator involved in overgrowth and malignant progression of the lung cancer cells through ROS production due to 9,10-PQ redox-cycling. - Highlights: • 9,10-PQ promotes invasion, metastasis and tumorigenicity in lung cancer cells. • The 9,10-PQ-elicited promotion is possibly due to AKR1B10 up-regulation

  6. The effect of acute dichlorodiphenyltrichloroethane exposure on hypermethylation status and down-regulation of p53 and p16(INK4a) genes in rat liver.

    PubMed

    Kostka, Grażyna; Urbanek-Olejnik, Katarzyna; Liszewska, Monika; Winczura, Alicja

    2016-05-01

    The aim of the study was to investigate the early effect of acute dichlorodiphenyltrichloroethane (DDT) exposure on the methylation status of the promoter region of two tumor suppressor genes: p53 and p16(INK4a) (p16) in rat liver. We analyzed their transcript and protein expression profiles concurrently with the examination of transcriptional and protein expression levels of DNA (cytosine-5)-methyltransferase 1 (Dnmt1). Male Wistar rats were treated with a single dose of DDT (57 mg kg(-1) of body weight) and the methylation status of p53 and p16 genes was examined after 24 h using methylation-sensitive restriction analysis-MSRA. The obtained results indicate that DDT induced alternations in methylation of the promoter region in both p53 and p16 genes. In all the tested samples, the promoter CpG islands of p53 (-261, -179, and -450) were methylated within 100% as compared to control samples (0%). The methylation status of the p16 promoter (-11 and +77) was also altered due to exposure to DDT. Methylated cytosines were detectable in 75% of the tested DNA samples. The Real-time PCR and western blot analyses showed a decrease in mRNA and protein levels of p53, respectively, which was related to the increase in DNA synthesis. These relationships were also observed for mRNA and protein expressions of p16, although to a slighter extent. We also showed that hypermethylation in the promoter region of both tumor suppressor genes was consistent with an increased Dnmt1 mRNA level, and this relationship was further confirmed at the protein level of DNMT1. Concluding, our data suggests that epigenetically mediated changes in gene expression may play an important role in the mechanism of DDT toxicity, including carcinogenic action. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 584-592, 2016. PMID:25410620

  7. Exposure to rosiglitazone, a PPAR-γ agonist, in late gestation reduces the abundance of factors regulating cardiac metabolism and cardiomyocyte size in the sheep fetus.

    PubMed

    Lie, Shervi; Hui, Melisa; McMillen, I Caroline; Muhlhausler, Beverly S; Posterino, Giuseppe S; Dunn, Stacey L; Wang, Kimberley C; Botting, Kimberley J; Morrison, Janna L

    2014-03-15

    It is unknown whether cardiomyocyte hypertrophy and the transition to fatty acid oxidation as the main source of energy after birth is dependent on the maturation of the cardiomyocytes' metabolic system, or on the limitation of substrate availability before birth. This study aimed to investigate whether intrafetal administration of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, rosiglitazone, during late gestation can stimulate the expression of factors regulating cardiac growth and metabolism in preparation for birth, and the consequences of cardiac contractility in the fetal sheep at ∼140 days gestation. The mRNA expression and protein abundance of key factors regulating growth and metabolism were quantified using quantitative RT-PCR and Western blot analysis, respectively. Cardiac contractility was determined by measuring the Ca(2+) sensitivity and maximum Ca(2+)-activated force of skinned cardiomyocyte bundles. Rosiglitazone-treated fetuses had a lower cardiac abundance of insulin-signaling molecules, including insulin receptor-β, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 (Tyr-895), phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, PI3K catalytic subunit p110α, phospho-3-phosphoinositide-dependent protein kinase 1 (Ser-241), protein kinase B (Akt-1), phospho-Akt (Ser-273), PKCζ, phospho-PKCζ(Thr-410), Akt substrate 160 kDa (AS160), phospho-AS160 (Thr-642), and glucose transporter type-4. Additionally, cardiac abundance of regulators of fatty acid β-oxidation, including adiponectin receptor 1, AMPKα, phospho-AMPKα (Thr-172), phospho-acetyl CoA carboxylase (Ser-79), carnitine palmitoyltransferase-1, and PGC-1α was lower in the rosiglitazone-treated group. Rosiglitazone administration also resulted in a decrease in cardiomyocyte size. Rosiglitazone administration in the late-gestation sheep fetus resulted in a decreased abundance of factors regulating cardiac glucose uptake, fatty acid β-oxidation, and

  8. Poor Rural Children Attract Close Study

    ERIC Educational Resources Information Center

    Viadero, Debra

    2008-01-01

    Growing up poor in isolated rural areas and small towns is qualitatively different from growing up poor in the city. Yet most of what experts know about the effects of poverty on children's development comes from studies conducted in big cities. Now, an ambitious project run by universities in Pennsylvania and North Carolina is putting what some…

  9. Extent of Malnourishment among the Rural Poor.

    ERIC Educational Resources Information Center

    Shotland, Jeffrey

    1989-01-01

    Uses national survey data to demonstrate that, compared to the rural or U.S. non-poor, the rural poor consumed less of eight of nine key nutrients; and disparities were greatest for vitamins A and C, iron, and calcium, and for the youngest (two-five years) age group studied. (SV)

  10. Colorectal poorly differentiated neuroendocrine carcinomas frequently exhibit BRAF mutations and are associated with poor overall survival.

    PubMed

    Olevian, Dane C; Nikiforova, Marina N; Chiosea, Simon; Sun, Weijing; Bahary, Nathan; Kuan, Shih-Fan; Pai, Reetesh K

    2016-03-01

    The molecular alterations in colorectal poorly differentiated neuroendocrine carcinoma remain incompletely characterized, particularly with respect to mutations in BRAF and KRAS. We analyzed 32 colorectal poorly differentiated neuroendocrine carcinomas and 40 colorectal poorly differentiated conventional adenocarcinomas for mutations in KRAS and BRAF and for DNA mismatch repair protein abnormalities to correlate histopathology with molecular alterations and survival. Compared with poorly differentiated conventional adenocarcinoma, poorly differentiated neuroendocrine carcinoma frequently harbored BRAF mutations (59% versus 5%; P < .001) and less frequently demonstrated KRAS codon 12 or 13 mutations (17% versus 43%; P = .03). BRAF mutations were identified in both pure poorly differentiated neuroendocrine carcinoma (60%) and poorly differentiated neuroendocrine carcinoma associated with a signet ring cell adenocarcinoma component (82%). Most (93%) poorly differentiated neuroendocrine carcinomas demonstrated proficient DNA mismatch repair by either microsatellite instability polymerase chain reaction or DNA mismatch repair immunohistochemistry. Patients with poorly differentiated neuroendocrine carcinoma had a significantly worse overall survival compared with patients with poorly differentiated conventional adenocarcinoma (P < .001). There was no significant difference in overall survival between patients with pure poorly differentiated neuroendocrine carcinoma and patients with both poorly differentiated neuroendocrine carcinoma and adenocarcinoma components (P = .5). In conclusion, colorectal poorly differentiated neuroendocrine carcinomas frequently harbor BRAF mutations and are associated with poor overall survival. PMID:26826419

  11. Time estimation in good and poor sleepers.

    PubMed

    Fichten, Catherine S; Creti, Laura; Amsel, Rhonda; Bailes, Sally; Libman, Eva

    2005-12-01

    Time estimation was examined in 148 older good and poor sleepers in analogue and naturalistic sleep settings. On analogue tasks, both "empty" time and time listening to an audiobook were overestimated by both good and poor sleepers. There were no differences between groups. "Empty" time was experienced as "dragging." In the sleep setting, most poor sleepers underestimated nocturnal sleep and overestimated awake times related to their own sleep problem: sleep onset vs. sleep maintenance insomnia. Good sleepers did the opposite. Severity of sleep problem and size of time estimation errors were unrelated. Greater night-to-night wake time variability was experienced by poor than by good sleepers. Psychological adjustment was unrelated to time estimations and to magnification or minimization of sleep problems. The results suggest that for poor sleepers who magnify their sleep problem, self-monitoring can be of benefit by demonstrating that the sleep problem is not as severe as believed. PMID:16320096

  12. Comparison of gene expression regulation in mouse- and human embryonic stem cell assays during neural differentiation and in response to valproic acid exposure.

    PubMed

    Schulpen, Sjors H W; Theunissen, Peter T; Pennings, Jeroen L A; Piersma, Aldert H

    2015-08-15

    Embryonic stem cell tests (EST) are considered promising alternative assays for developmental toxicity testing. Classical mouse derived assays (mEST) are being replaced by human derived assays (hEST), in view of their relevance for human hazard assessment. We have compared mouse and human neural ESTn assays for neurodevelopmental toxicity as to regulation of gene expression during cell differentiation in both assays. Commonalities were observed in a range of neurodevelopmental genes and gene ontology (GO) terms. The mESTn showed a higher specificity in neurodevelopment than the hESTn, which may in part be caused by necessary differences in test protocols. Moreover, gene expression responses to the anticonvulsant and human teratogen valproic acid were compared. Both assays detected pharmacological and neurodevelopmental gene sets regulated by valproic acid. Common significant expression changes were observed in a subset of homologous neurodevelopmental genes. We suggest that these genes and related GO terms may provide good candidates for robust biomarkers of neurodevelopmental toxicity in hESTn. PMID:26072468

  13. MicroRNA-216b/Beclin 1 axis regulates autophagy and apoptosis in human Tenon's capsule fibroblasts upon hydroxycamptothecin exposure.

    PubMed

    Xu, Xinyu; Fu, Yuxuan; Tong, Jun; Fan, Shuxin; Xu, Kai; Sun, Hong; Liang, Ya; Yan, Chuqi; Yuan, Zhilan; Ge, Yingbin

    2014-06-01

    Proliferation and fibrosis of human Tenon's fibroblasts (HTFs) have significantly challenged the outcome of glaucoma filtration surgery. Hydroxycamptothecin (HCPT) is considered as a potential chemical to overcome this issue as it was previously shown that HCPT inhibited cell proliferation and induced apoptosis in fibroblasts. Here, we further dissected the molecular pathway, through which the HCPT inhibit the proliferation of HTFs. We showed that HCPT induced significant autophagy as well as apoptosis, two self-destructive processes, and down-regulated the expression of miR-216b in HTFs. Overexpression of miR-216b in HTFs suppressed the autophagy and apoptosis induced by HCPT, whereas silence of miR-216b led to effects that were similar to those caused by the treatment with HCPT. Further, we showed that miR-216b could directly target a specific fragment in the 3' untranslated region of Beclin 1 as demonstrated by luciferase assay, and consequently decreased the expression of Beclin 1. Consistently, knocking down Beclin 1 significantly decreased HCPT-triggered autophagy and apoptosis, and increased the viability of HTFs treated with HCPT, thus implicating that Beclin 1 functions as a pro-apoptotic molecule in this circumstance. Altogether, we concluded that miR-216b regulated both autophagy and apoptosis by modulating Beclin 1 in HTFs treated with HCPT. We also demonstrated that HCPT-induced autophagy is one of the agent's anti-proliferative effects. PMID:24681041

  14. Chronic exposure to Rhodobacter sphaeroides extract Lycogen™ prevents UVA-induced malondialdehyde accumulation and procollagen I down-regulation in human dermal fibroblasts.

    PubMed

    Yang, Tsai-Hsiu; Lai, Ying-Hsiu; Lin, Tsuey-Pin; Liu, Wen-Sheng; Kuan, Li-Chun; Liu, Chia-Chyuan

    2014-01-01

    UVA contributes to the pathogenesis of skin aging by downregulation of procollagen I content and induction of matrix metalloproteinase (MMP)-associated responses. Application of antioxidants such as lycopene has been demonstrated as a convenient way to achieve protection against skin aging. Lycogen™, derived from the extracts of Rhodobacter sphaeroides, exerts several biological effects similar to that of lycopene whereas most of its anti-aging efficacy remains uncertain. In this study, we attempted to examine whether Lycogen™ could suppress malondialdehyde (MDA) accumulation and restore downregulated procollagen I expression induced by UVA exposure. In human dermal fibroblasts Hs68 cells, UVA repressed cell viability and decreased procollagen I protein content accompanied with the induction of MMP-1 and MDA accumulation. Remarkably, incubation with 50 µM Lycogen™ for 24 h ameliorated UVA-induced cell death and restored UVA-induced downregulation of procollagen in a dose-related manner. Lycogen™ treatment also prevented the UVA-induced MMP-1 upregulation and intracellular MDA generation in Hs68 cells. Activation of NFκB levels, one of the downstream events induced by UVA irradiation and MMP-1 induction, were also prevented by Lycogen™ administration. Taken together, our findings demonstrate that Lycogen™ may be an alternative agent that prevents UVA-induced skin aging and could be used in cosmetic and pharmaceutical applications. PMID:24463291

  15. NORM regulations

    SciTech Connect

    Gray, P.

    1997-02-01

    The author reviews the question of regulation for naturally occuring radioactive material (NORM), and the factors that have made this a more prominent concern today. Past practices have been very relaxed, and have often involved very poor records, the involvment of contractors, and the disposition of contaminated equipment back into commercial service. The rationale behind the establishment of regulations is to provide worker protection, to exempt low risk materials, to aid in scrap recycling, to provide direction for remediation and to examine disposal options. The author reviews existing regulations at federal and state levels, impending legislation, and touches on the issue of site remediation and potential liabilities affecting the release of sites contaminated by NORM.

  16. Community Violence Exposure and Children's Academic Functioning.

    ERIC Educational Resources Information Center

    Schwartz, David; Gorman, Andrea Hopmeyer

    2003-01-01

    Reports a cross-sectional investigation of the link between community violence exposure and academic difficulties for 237 urban elementary school children. Analyses indicated that community violence exposure was associated with poor academic performance. These relations appear to be mediated by symptoms of depression and disruptive behavior.…

  17. Dietary Exposure to 2,2′,4,4′-Tetrabromodiphenyl Ether (PBDE-47) Alters Thyroid Status and Thyroid Hormone–Regulated Gene Transcription in the Pituitary and Brain

    PubMed Central

    Lema, Sean C.; Dickey, Jon T.; Schultz, Irvin R.; Swanson, Penny

    2008-01-01

    Background Polybrominated diphenyl ether (PBDE) flame retardants have been implicated as disruptors of the hypothalamic-pituitary-thyroid axis. Animals exposed to PBDEs may show reduced plasma thyroid hormone (TH), but it is not known whether PBDEs impact TH-regulated pathways in target tissues. Objective We examined the effects of dietary exposure to 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47)—commonly the highest concentrated PBDE in human tissues—on plasma TH levels and on gene transcripts for glycoprotein hormone α-subunit (GPHα) and thyrotropin β-subunit (TSHβ) in the pituitary gland, the autoinduced TH receptors α and β in the brain and liver, and the TH-responsive transcription factor basic transcription element-binding protein (BTEB) in the brain. Methods Breeding pairs of adult fathead minnows (Pimephales promelas) were given dietary PBDE-47 at two doses (2.4 μg/pair/day or 12.3 μg/pair/day) for 21 days. Results Minnows exposed to PBDE-47 had depressed plasma thyroxine (T4), but not 3,5,3′-triiodothyronine (T3). This decline in T4 was accompanied by elevated mRNA levels for TStHβ (low dose only) in the pituitary. PBDE-47 intake elevated transcript for TH receptor αin the brain of females and decreased mRNA for TH receptor β in the brain of both sexes, without altering these transcripts in the liver. In males, PBDE-47 exposure also reduced brain transcripts for BTEB. Conclusions Our results indicate that dietary exposure to PBDE-47 alters TH signaling at multiple levels of the hypothalamic-pituitary-thyroid axis and provide evidence that TH-responsive pathways in the brain may be particularly sensitive to disruption by PBDE flame retardants. PMID:19079722

  18. Exposure of E. coli to DNA-Methylating Agents Impairs Biofilm Formation and Invasion of Eukaryotic Cells via Down Regulation of the N-Acetylneuraminate Lyase NanA.

    PubMed

    Di Pasquale, Pamela; Caterino, Marianna; Di Somma, Angela; Squillace, Marta; Rossi, Elio; Landini, Paolo; Iebba, Valerio; Schippa, Serena; Papa, Rosanna; Selan, Laura; Artini, Marco; Palamara, Anna Teresa; Palamara, Annateresa; Duilio, Angela

    2016-01-01

    DNA methylation damage can be induced by endogenous and exogenous chemical agents, which has led every living organism to develop suitable response strategies. We investigated protein expression profiles of Escherichia coli upon exposure to the alkylating agent methyl-methane sulfonate (MMS) by differential proteomics. Quantitative proteomic data showed a massive downregulation of enzymes belonging to the glycolytic pathway and fatty acids degradation, strongly suggesting a decrease of energy production. A strong reduction in the expression of the N-acetylneuraminate lyases (NanA) involved in the sialic acid metabolism was also observed. Using a null NanA mutant and DANA, a substrate analog acting as competitive inhibitor, we demonstrated that down regulation of NanA affects biofilm formation and adhesion properties of E. coli MV1161. Exposure to alkylating agents also decreased biofilm formation and bacterial adhesion to Caco-2 eukaryotic cell line by the adherent invasive E. coli (AIEC) strain LF82. Our data showed that methylation stress impairs E. coli adhesion properties and suggest a possible role of NanA in biofilm formation and bacteria host interactions. PMID:26904018

  19. Exposure of E. coli to DNA-Methylating Agents Impairs Biofilm Formation and Invasion of Eukaryotic Cells via Down Regulation of the N-Acetylneuraminate Lyase NanA

    PubMed Central

    Di Pasquale, Pamela; Caterino, Marianna; Di Somma, Angela; Squillace, Marta; Rossi, Elio; Landini, Paolo; Iebba, Valerio; Schippa, Serena; Papa, Rosanna; Selan, Laura; Artini, Marco; Palamara, Anna Teresa; Duilio, Angela

    2016-01-01

    DNA methylation damage can be induced by endogenous and exogenous chemical agents, which has led every living organism to develop suitable response strategies. We investigated protein expression profiles of Escherichia coli upon exposure to the alkylating agent methyl-methane sulfonate (MMS) by differential proteomics. Quantitative proteomic data showed a massive downregulation of enzymes belonging to the glycolytic pathway and fatty acids degradation, strongly suggesting a decrease of energy production. A strong reduction in the expression of the N-acetylneuraminate lyases (NanA) involved in the sialic acid metabolism was also observed. Using a null NanA mutant and DANA, a substrate analog acting as competitive inhibitor, we demonstrated that down regulation of NanA affects biofilm formation and adhesion properties of E. coli MV1161. Exposure to alkylating agents also decreased biofilm formation and bacterial adhesion to Caco-2 eukaryotic cell line by the adherent invasive E. coli (AIEC) strain LF82. Our data showed that methylation stress impairs E. coli adhesion properties and suggest a possible role of NanA in biofilm formation and bacteria host interactions. PMID:26904018

  20. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring

    PubMed Central

    Borengasser, Sarah J.; Faske, Jennifer; Kang, Ping; Blackburn, Michael L.; Badger, Thomas M.

    2014-01-01

    The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (∼16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)α, PGC1β, and estrogen-related receptor (ERR)α], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life. PMID:25336449

  1. How School Taught Me I Was Poor

    ERIC Educational Resources Information Center

    Sapp, Jeff

    2009-01-01

    In this article, the author recounts how school taught him that he was poor. For him, third grade was the year in which he learned in school that he was poor. The author's story reminds everyone that all children do not experience school in the same way. Their social class (in the case described in this article), as well as their race, gender,…

  2. Constraining the Evolution of Poor Clusters

    NASA Astrophysics Data System (ADS)

    Broming, Emma J.; Fuse, C. R.

    2012-01-01

    There currently exists no method by which to quantify the evolutionary state of poor clusters (PCs). Research by Broming & Fuse (2010) demonstrated that the evolution of Hickson compact groups (HCGs) are constrained by the correlation between the X-ray luminosities of point sources and diffuse gas. The current investigation adopts an analogous approach to understanding PCs. Plionis et al. (2009) proposed a theory to define the evolution of poor clusters. The theory asserts that cannibalism of galaxies causes a cluster to become more spherical, develop increased velocity dispersion and increased X-ray temperature and gas luminosity. Data used to quantify the evolution of the poor clusters were compiled across multiple wavelengths. The sample includes 162 objects from the WBL catalogue (White et al. 1999), 30 poor clusters in the Chandra X-ray Observatory archive, and 15 Abell poor clusters observed with BAX (Sadat et al. 2004). Preliminary results indicate that the cluster velocity dispersion and X-ray gas and point source luminosities can be used to highlight a weak correlation. An evolutionary trend was observed for multiple correlations detailed herein. The current study is a continuation of the work by Broming & Fuse examining point sources and their properties to determine the evolutionary stage of compact groups, poor clusters, and their proposed remnants, isolated ellipticals and fossil groups. Preliminary data suggests that compact groups and their high-mass counterpart, poor clusters, evolve along tracks identified in the X-ray gas - X-ray point source relation. While compact groups likely evolve into isolated elliptical galaxies, fossil groups display properties that suggest they are the remains of fully coalesced poor clusters.

  3. Overcoming challenges of catastrophe modelling in data poor regions

    NASA Astrophysics Data System (ADS)

    Grassby, L.; Millinship, I.; Breinl, K.

    2012-04-01

    There is an increasing demand for loss accumulation tools in expanding international insurance markets such as India, China and Thailand. This reflects the combination of an increase in exposures in these territories as industry intensifies and urban development expands, as well as several notable natural catastrophes affecting these areas over the past few years (e.g. extreme floods in Mumbai in 2006 and in Thailand in 2011). Large, global insurers and reinsurers are embracing the opportunity to underwrite these exposures but only where adequate tools are available to provide understanding of the hazards, exposures and potential losses. Unlike more developed countries, data availability in these regions is typically limited and of poor resolution, but model development is still required in order to analyse the risk. Some of the modelling challenges associated with data limitations include: (1) dealing with a lack of hydrological data which results in greater uncertainty of the flow rate and event frequency; (2) lower DTM resolution than that available across much of Europe, which underlies the hazard component of the catastrophe model; (3) limited accessibility to data that characterises the Built Environment including information on different building types and their susceptibility to damage; and (4) a lack of claims data from previous events or engineering research into the vulnerability of different building types. This is used to generate of country and structure specific vulnerability curves that explain the relationship between hazard intensity and damages. By presenting an industry specific flood model for data-poor India in collaboration with Allianz Re, we illustrate how we have overcome many of these challenges to allow loss accumulations to be made. The resulting model was successfully validated against the floods in Mumbai and Surat in 2006 and is being developed further with the availability of new data.

  4. Environmental and Occupational Exposures in Immigrant Health

    PubMed Central

    Eamranond, Pracha P.; Hu, Howard

    2008-01-01

    Immigrants comprise vulnerable populations that are frequently exposed to a multitude of environmental and occupational hazards. The historical context behind state and federal legislation has helped to foster an environment that is particularly hostile toward caring for immigrant health. Current hazards include toxic exposures, air and noise pollution, motor vehicle accidents, crowded living and work environments with inadequate ventilation, poor sanitation, mechanical injury, among many others. Immigrants lack the appropriate training, materials, health care access, and other resources to reduce their exposure to preventable environmental and occupational health risks. This dilemma is exacerbated by current anti-immigrant sentiments, miscommunication between native and immigrant populations, and legislation denying immigrants access to publicly funded medical care. Given that current health policy has failed to address immigrant health appropriately and political impetus is lacking, efforts should also focus on alternative solutions, including organized labor. Labor unions that serve to educate workers, survey work environments, and defend worker rights will greatly alleviate and prevent the burden of disease incurred by immigrants. The nation’s health will benefit from improved regulation of living and workplace environments to improve the health of immigrants, regardless of legal status. PMID:21572847

  5. Cyclic diGMP Regulates Production of Sortase Substrates of Clostridium difficile and Their Surface Exposure through ZmpI Protease-mediated Cleavage*

    PubMed Central

    Peltier, Johann; Shaw, Helen A.; Couchman, Edward C.; Dawson, Lisa F.; Yu, Lu; Choudhary, Jyoti S.; Kaever, Volkhard; Wren, Brendan W.; Fairweather, Neil F.

    2015-01-01

    In Gram-positive pathogens, surface proteins may be covalently anchored to the bacterial peptidoglycan by sortase, a cysteine transpeptidase enzyme. In contrast to other Gram-positive bacteria, only one single sortase enzyme, SrtB, is conserved between strains of Clostridium difficile. Sortase-mediated peptidase activity has been reported in vitro, and seven potential substrates have been identified. Here, we demonstrate the functionality of sortase in C. difficile. We identify two sortase-anchored proteins, the putative adhesins CD2831 and CD3246, and determine the cell wall anchor structure of CD2831. The C-terminal PPKTG sorting motif of CD2831 is cleaved between the threonine and glycine residues, and the carboxyl group of threonine is amide-linked to the side chain amino group of diaminopimelic acid within the peptidoglycan peptide stem. We show that CD2831 protein levels are elevated in the presence of high intracellular cyclic diGMP (c-diGMP) concentrations, in agreement with the control of CD2831 expression by a c-diGMP-dependent type II riboswitch. Low c-diGMP levels induce the release of CD2831 and presumably CD3246 from the surface of cells. This regulation is mediated by proteolytic cleavage of CD2831 and CD3246 by the zinc metalloprotease ZmpI, whose expression is controlled by a type I c-diGMP riboswitch. These data reveal a novel regulatory mechanism for expression of two sortase substrates by the secondary messenger c-diGMP, on which surface anchoring is dependent. PMID:26283789

  6. Designing Targeted Educational Voucher Schemes for the Poor in Developing Countries

    ERIC Educational Resources Information Center

    Shafiq, M. Najeeb

    2009-01-01

    Targeted educational voucher schemes [TEVS] are often proposed for poor children in developing countries. This article explores the design of an effective TEVS using three policy instruments: regulation, support services, and finance. The regulation design addresses the rules that must be adhered to by participating households, children, and…

  7. Why so many children are poor.

    PubMed

    Betson, D M; Michael, R T

    1997-01-01

    According to the official U.S. measure of poverty, in 1995 the child poverty rate in this country was nearly 21%, compared with an adult poverty rate of 11%. This article explores why, according to the official measure, there are so many poor children. Working from the premise that children are poor because they live with poor adults, the reasons for adult poverty are reviewed. Both economic forces and demographic trends have contributed to growing inequality of earnings among workers. That inequality coupled with stagnating real earnings has increased poverty. In addition, education, age, and race affect an individual's earning capacity; the article examines the likelihood that an individual will earn enough to keep his or her family out of poverty, given the individual's educational attainment, age, and race. The reasons for the large difference between the child and adult poverty rates are explored, using a decomposition of the poverty population to show how demographic characteristics such as higher fertility rates among poor families and the higher prevalence of single-parent families among the poor lead to substantially higher poverty rates for children than for adults. Finally, the article examines the validity of the official poverty measure and reviews how an alternative measure proposed by a National Research Council panel would address the official measure's shortcomings. If the panel's proposed measure were adopted, it would change the statistical face of poor children. It would, for example, show an increase in the proportion of poor children who live in families with two parents and a corresponding decrease in the proportion in families with only one parent, and it would show an increase in the proportion of children who live in families with at least one full-time employed adult and a corresponding decrease in the proportion in families with no adult employed full time. PMID:9299835

  8. Photometric Properties of Galaxies in Poor Clusters

    NASA Astrophysics Data System (ADS)

    Sharma, M.; Prabhu, T.

    We study several statistical properties of galaxies in four poor clusters of galaxies using optical photometry. We select these poor clusters as luminous, extended X-ray sources identified with poor galaxy systems in the EMSS catalogue of clusters of galaxies. The clusters are at moderate redshifts (0.08poor clusters, but steeper than the field LF in the R-band. In terms of the statistical properties of their member galaxies, poor clusters appear to be lower-mass extensions of their rich counterparts.

  9. Maternal abuse history and self-regulation difficulties in preadolescence.

    PubMed

    Delker, Brianna C; Noll, Laura K; Kim, Hyoun K; Fisher, Philip A

    2014-12-01

    Although poor parenting is known to be closely linked to self-regulation difficulties in early childhood, comparatively little is understood about the role of other risk factors in the early caregiving environment (such as a parent's own experiences of childhood abuse) in developmental pathways of self-regulation into adolescence. Using a longitudinal design, this study aimed to examine how a mother's history of abuse in childhood relates to her offspring's self-regulation difficulties in preadolescence. Maternal controlling parenting and exposure to intimate partner aggression in the child's first 24-36 months were examined as important early social and environmental influences that may explain the proposed connection between maternal abuse history and preadolescent self-regulation. An ethnically diverse sample of mothers (N=488) who were identified as at-risk for child maltreatment was recruited at the time of their children's birth. Mothers and their children were assessed annually from the child's birth through 36 months, and at age 9-11 years. Structural equation modeling and bootstrap tests of indirect effects were conducted to address the study aims. Findings indicated that maternal abuse history indirectly predicted their children's self-regulation difficulties in preadolescence mainly through maternal controlling parenting in early childhood, but not through maternal exposure to aggression by an intimate partner. Maternal history of childhood abuse and maternal controlling parenting in her child's early life may have long-term developmental implications for child self-regulation. PMID:25459984

  10. English as a Foreign Language Spelling: Comparisons between Good and Poor Spellers

    ERIC Educational Resources Information Center

    Russak, Susie; Kahn-Horwitz, Janina

    2015-01-01

    This study examined English as a foreign language (EFL) spelling development amongst 233 fifth-grade, eighth-grade and 10th-grade Hebrew first-language speakers to examine effects of English orthographic exposure on spelling. Good and poor speller differences were examined regarding the acquisition of novel phonemes (/ae/, /?/ and /?/) and…

  11. Criminal exposure.

    PubMed

    1999-08-01

    A 39-year-old man who had sex with a 16-year-old boy, was sentenced to five years in prison. The defendant pleaded guilty to statutory rape and criminal exposure to HIV. The boy discovered that the man was taking HIV medications, and the man subsequently disclosed his treatment after being arrested. PMID:11367003

  12. EXPOSURE ANALYSIS

    EPA Science Inventory

    This proceedings chapter will discuss the state-of-the-science regarding the evaluation of exposure as it relates to water quality criteria (WQC), sediment quality guidelines (SQG), and wildlife criteria (WC). Throughout this discussion, attempts are made to identify the methods ...

  13. Hypotonic exposures.

    PubMed

    Flynn, W J; Hill, R M

    1984-03-01

    Even without a contact lens, the cornea can suffer adverse physiological changes from hypotonic exposure, as well as the associated subjective phenomena (e.g., halo and rainbows). The contact lens adds a dimension to this problem that should be viewed against a background of normal (non-wearing) susceptibilities. PMID:6715776

  14. Regulation of Hsp27 and Hsp70 expression in human and mouse skin construct models by caveolae following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

    SciTech Connect

    Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

    2011-06-01

    Dermal exposure to the vesicant sulfur mustard causes marked inflammation and tissue damage. Basal keratinocytes appear to be a major target of sulfur mustard. In the present studies, mechanisms mediating skin toxicity were examined using a mouse skin construct model and a full-thickness human skin equivalent (EpiDerm-FT{sup TM}). In both systems, administration of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide (CEES, 100-1000 {mu}M) at the air surface induced mRNA and protein expression of heat shock proteins 27 and 70 (Hsp27 and Hsp70). CEES treatment also resulted in increased expression of caveolin-1, the major structural component of caveolae. Immunohistochemistry revealed that Hsp27, Hsp70 and caveolin-1 were localized in basal and suprabasal layers of the epidermis. Caveolin-1 was also detected in fibroblasts in the dermal component of the full thickness human skin equivalent. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that Hsp27 and Hsp70 were localized in caveolae. Treatment of mouse keratinocytes with filipin III or methyl-{beta}-cyclodextrin, which disrupt caveolar structure, markedly suppressed CEES-induced Hsp27 and Hsp70 mRNA and protein expression. CEES treatment is known to activate JNK and p38 MAP kinases; in mouse keratinocytes, inhibition of these enzymes suppressed CEES-induced expression of Hsp27 and Hsp70. These data suggest that MAP kinases regulate Hsp 27 and Hsp70; moreover, caveolae-mediated regulation of heat shock protein expression may be important in the pathophysiology of vesicant-induced skin toxicity.

  15. Resilient Parenting: Overcoming Poor Parental Bonding

    ERIC Educational Resources Information Center

    Travis, Wendy J.; Combs-Orme, Terri

    2007-01-01

    This study identified groups of mothers with varying patterns of adaptive functioning and bonds with their own parents. These patterns were related to mothers' parenting of their own children to understand how some mothers avoid repeating the cycle of poor parenting. Data from 210 new mothers were analyzed before hospital discharge about bonding…

  16. Planning Behaviour in Good and Poor Readers

    ERIC Educational Resources Information Center

    Mahapatra, Shamita

    2016-01-01

    A group of 50 good readers and a group of 50 poor readers of Grade 5 matched for age and intelligence and selected on the basis of their proficiency in reading comprehension were tested for their competence in word reading and the process of planning at three different levels, namely, perceptual, memory and conceptual in order to study the…

  17. Runway hazard detection in poor visibility conditions

    NASA Astrophysics Data System (ADS)

    Jiang, Bo; Rahman, Zia-ur

    2012-01-01

    More recently, research on enhancing the situational awareness of pilots, especially in poor visibility flight conditions, gains more and more interests. Since pilots may not be able to spot the runway clearly in poor visibility conditions, such as fog, smoke, haze or dim lighting conditions, aviation landing problem can occur due to the (unexpected) presence of objects on the runway. Complicated and trivial instruments, switches, bottoms, plus sudden happenings are enough for the pilots to take care of during landing approach. Therefore, an automatic hazard detection approach that combines non-linear Multi-scale Retinex (MSR) image enhancement, edge detection with basic edge pattern analysis, and image analysis is investigated. The effect of applying the enhancement method is to make the image of the runway almost independent from the poor atmospheric conditions. The following smart edge detection process extracts edge information, which can also reduce the storing space, the comparison and retrieval time, and the effect of sensor noise. After analyzing the features existing in the edge differences occurring in the runway area by digital image processing techniques, the existing potential hazard will be localized and labeled. Experimental results show that the proposed approach is effective in runway hazard detection in poor visibility conditions.

  18. From Many Lands. Voices of the Poor.

    ERIC Educational Resources Information Center

    Narayan, Deepa, Ed.; Petesch, Patti, Ed.

    This book, the last volume in a three-part series, draws on a large-scale worldwide poverty study to present the views, experiences, and aspirations of poor people in 14 selected countries. In each country, interviews and discussion groups were held in 8-15 rural and urban communities that reflected the most prevalent poverty groups and the…

  19. Who Are The Poor In Puerto Rico?

    ERIC Educational Resources Information Center

    Levine, Barry B.; de Cintron, Celia F.

    Dichotomous poverty is defined by taking an arbitrary standard of consumption capability as a dividing line between rich and poor. An investigation into dichotomous poverty below the 2000 dollar level will be worthwhile, since, in 1953, the Planning Board announced as a goal the attempt to lift all families above this margin. In 1953, 78 percent…

  20. University Students with Poor Reading Comprehension

    ERIC Educational Resources Information Center

    Georgiou, George K.; Das, J. P.

    2015-01-01

    The present study aimed to examine the nature of the working memory and general cognitive ability deficits experienced by university students with a specific reading comprehension deficit. A total of 32 university students with poor reading comprehension but average word-reading skills and 60 age-word-matched controls with no comprehension…

  1. The Other Poor: Rural Poverty and Education.

    ERIC Educational Resources Information Center

    Books, Sue

    1997-01-01

    This paper argues that rural poverty remains relatively invisible because, although shameful, it is profitable, and the rural poor pose little threat to their suburban neighbors. This is illustrated via interrogation concerning a rural poultry plant fire. The paper examines implications of this case for foundations scholars and educational…

  2. Choosing among Alternative Programs for Poor Children.

    ERIC Educational Resources Information Center

    Currie, Janet M.

    1997-01-01

    Suggests four criteria (efficiency, return on investment, incentives, and equity) for evaluating and comparing public programs for poor children, and provides an overview of information available on eight large federal programs using these criteria. Positive effects of some programs are noted, and policy recommendations the evidence supports are…

  3. Correcting Poor Posture without Awareness or Willpower

    ERIC Educational Resources Information Center

    Wernik, Uri

    2012-01-01

    In this article, a new technique for correcting poor posture is presented. Rather than intentionally increasing awareness or mobilizing willpower to correct posture, this approach offers a game using randomly drawn cards with easy daily assignments. A case using the technique is presented to emphasize the subjective experience of living with poor…

  4. Getting to Know L2 Poor Comprehenders

    ERIC Educational Resources Information Center

    Zoghi, Masoud; Mustapha, Ramlee; Maasum, Tengku Nor Rizan BT Tengku Mohamad

    2011-01-01

    Among the plethora of studies conducted thus far to explore the factors affecting EFL reading effectiveness, scant attention seems to be paid to the why of poor reading comprehension of most EFL learners. In this regard, the present article capitalized on qualitative research on a small scale, for the purpose of addressing the not-so-often debated…

  5. Katharine Drexel: Learning to Love the Poor

    ERIC Educational Resources Information Center

    Murray, Cecilia

    2006-01-01

    Although born into privilege, Katharine Drexel was blessed with parents, siblings, friends, and spiritual guides who kept her rooted in a deep, Eucharistic faith. Responding to the needs of the poor was a responsibility of the rich, and Katharine learned this value at the hands of her parents at an early age. With the good counsel of popes and…

  6. EEG Power Spectra of Adolescent Poor Readers.

    ERIC Educational Resources Information Center

    Ackerman, Peggy T.; McPherson, W. Brian; Oglesby, D. Michael; Dykman, Roscoe A.

    1998-01-01

    Electroencephalographic power spectra were studied in two poor-reading adolescent groups (n=38), dysphonetic and phonetic. Significant Group x Hemisphere effects were found in the alpha and beta bands, with the phonetic group showing right greater than left asymmetry. Results suggest more circumscribed and mature processing in the phonetically…

  7. Photometric Properties of Poor Cluster Galaxies

    NASA Astrophysics Data System (ADS)

    Sharma, M.; Prabhu, T. P.

    2002-12-01

    We study several statistical properties of galaxies in four poor clusters of galaxies using multi-color optical photometry obtained at the Vainu Bappu Telescope, India. The clusters, selected from the EMSS Catalog, are at moderate redshifts (0.08 < z < 0.25), of equivalent Abell richness R=0, and appear to be dynamically young. The early-type galaxy populations are clearly evolved, as traced by the tightness of the color-magnitude relations and the accordance of the latter with those of the Virgo cluster. The blue galaxy fractions are similar to those of R=0 clusters and higher than those of richer clusters at similar redshifts. The composite luminosity functions (LFs) in B, V, and R bands are flat at the faint end, similar to the V-band LF derived by Yamagata & Maehara for other (MKW/AWM) poor clusters but steeper than the R-band field LF derived by Lin et al. In terms of the statistical properties of their member galaxies, poor clusters appear to be lower-mass extensions of their rich counterparts. The brightest galaxies of three of these poor clusters appear to be luminous ellipticals with no incontrovertible signatures of a halo. It is likely that they were formed from multiple mergers early in the history of the clusters.

  8. Promoting Upward Mobility for the Working Poor.

    ERIC Educational Resources Information Center

    Rupured, Michael

    2000-01-01

    The working poor are typically defined by researchers as individuals who work at least part of the year and earn less than a given percentage of the federal poverty level. This definition tends to understate the problem. In 1997, 15.8 million employed parents had incomes below 200 percent of the federal poverty level. The federal Earned Income Tax…

  9. Barely Getting By: Wisconsin's Working Poor Families.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Center on Wisconsin Strategy.

    Noting that 182,000 of Wisconsin's children are living below the poverty line, this report documents factors affecting the working poor of Wisconsin, combining labor market and wage data with profiles of families and their children from communities throughout the state. The report documents the surge in poverty-wage jobs in Wisconsin over the past…

  10. Residential Mobility among the Rural Poor.

    ERIC Educational Resources Information Center

    Fitchen, Janet M.

    1994-01-01

    The frequency of short-distance residential moves in poor rural New York counties was much greater than nationally, driven by scarce affordable housing and changes in personal and household situations. Higher frequency movement was associated with younger age, fewer children, and weaker social support networks. Discusses impacts of high mobility…

  11. Hardship financing of healthcare among rural poor in Orissa, India

    PubMed Central

    2012-01-01

    Background This study examines health-related "hardship financing" in order to get better insights on how poor households finance their out-of-pocket healthcare costs. We define hardship financing as having to borrow money with interest or to sell assets to pay out-of-pocket healthcare costs. Methods Using survey data of 5,383 low-income households in Orissa, one of the poorest states of India, we investigate factors influencing the risk of hardship financing with the use of a logistic regression. Results Overall, about 25% of the households (that had any healthcare cost) reported hardship financing during the year preceding the survey. Among households that experienced a hospitalization, this percentage was nearly 40%, but even among households with outpatient or maternity-related care around 25% experienced hardship financing. Hardship financing is explained not merely by the wealth of the household (measured by assets) or how much is spent out-of-pocket on healthcare costs, but also by when the payment occurs, its frequency and its duration (e.g. more severe in cases of chronic illnesses). The location where a household resides remains a major predictor of the likelihood to have hardship financing despite all other household features included in the model. Conclusions Rural poor households are subjected to considerable and protracted financial hardship due to the indirect and longer-term deleterious effects of how they cope with out-of-pocket healthcare costs. The social network that households can access influences exposure to hardship financing. Our findings point to the need to develop a policy solution that would limit that exposure both in quantum and in time. We therefore conclude that policy interventions aiming to ensure health-related financial protection would have to demonstrate that they have reduced the frequency and the volume of hardship financing. PMID:22284934

  12. 7 CFR 51.779 - Poorly colored.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946... not more than 25 percent of the surface may be of a solid dark green color....

  13. Parenting Efficacy and the Early School Adjustment of Poor and Near-Poor Black Children

    ERIC Educational Resources Information Center

    Jackson, Aurora P.; Choi, Jeong-Kyun; Bentler, Peter M.

    2009-01-01

    This short-term longitudinal study investigates whether maternal educational attainment, maternal employment status, and family income affect African American children's behavioral and cognitive functioning over time through their impacts on mothers' psychological functioning and parenting efficacy in a sample of 100 poor and near-poor single…

  14. Differences in Nutrient Adequacy among Poor and Non-Poor Children.

    ERIC Educational Resources Information Center

    Cook, John T.; Martin, Katie S.

    This study compared the proportion of 1- to 5-year-olds in poor and non-poor households whose intakes of key nutrients were inadequate. Data were obtained from the 1986 United States Department of Agriculture Nationwide Food Consumption Survey and Continuing Survey of Food Intakes by Individuals. An intake below 70 percent of the Recommended Daily…

  15. Longitudinal stability and predictors of poor oral comprehenders and poor decoders.

    PubMed

    Elwér, Sa; Keenan, Janice M; Olson, Richard K; Byrne, Brian; Samuelsson, Stefan

    2013-07-01

    Two groups of fourth-grade children were selected from a population sample (N=926) to be either poor oral comprehenders (poor oral comprehension but normal word decoding) or poor decoders (poor decoding but normal oral comprehension). By examining both groups in the same study with varied cognitive and literacy predictors, and examining them both retrospectively and prospectively, we could assess how distinctive and stable the predictors of each deficit are. Predictors were assessed retrospectively at preschool and at the end of kindergarten, Grade 1, and Grade 2. Group effects were significant at all test occasions, including those for preschool vocabulary (worse in poor oral comprehenders) and rapid automatized naming (RAN) (worse in poor decoders). Preschool RAN and vocabulary prospectively predicted Grade 4 group membership (77-79% correct classification) within the selected samples. Reselection in preschool of "at-risk" poor decoder and poor oral comprehender subgroups based on these variables led to significant but relatively weak prediction of subtype membership at Grade 4. Implications of the predictive stability of our results for identification and intervention of these important subgroups are discussed. PMID:23528975

  16. Longitudinal Stability and Predictors of Poor Oral Comprehenders and Poor Decoders

    PubMed Central

    Elwér, Åsa; Keenan, Janice M.; Olson, Richard K.; Byrne, Brian; Samuelsson, Stefan

    2012-01-01

    Two groups of 4th grade children were selected from a population sample (N= 926) to either be Poor Oral Comprehenders (poor oral comprehension but normal word decoding), or Poor Decoders (poor decoding but normal oral comprehension). By examining both groups in the same study with varied cognitive and literacy predictors, and examining them both retrospectively and prospectively, we could assess how distinctive and stable the predictors of each deficit are. Predictors were assessed retrospectively at preschool, at the end of kindergarten, 1st, and 2nd grades. Group effects were significant at all test occasions, including those for preschool vocabulary (worse in poor oral comprehenders) and rapid naming (RAN) (worse in poor decoders). Preschool RAN and Vocabulary prospectively predicted grade 4 group membership (77–79% correct classification) within the selected samples. Reselection in preschool of at-risk poor decoder and poor oral comprehender subgroups based on these variables led to significant but relatively weak prediction of subtype membership at grade 4. Implications of the predictive stability of our results for identification and intervention of these important subgroups are discussed. PMID:23528975

  17. Intimate partner violence and poor mental health among Thai women residing in Sweden

    PubMed Central

    Fernbrant, Cecilia; Emmelin, Maria; Essén, Birgitta; Östergren, Per-Olof; Cantor-Graae, Elizabeth

    2014-01-01

    Objectives The current aim is to examine the prevalence of intimate partner violence (IPV) among Thai women residing in Sweden and its association with mental health. We also investigate the potential influence of social isolation and social capital regarding the association between IPV and mental health outcome. Design A public health questionnaire in Thai was distributed by post to the entire population of Thai women, aged 18–64, residing in two regions in Sweden since 2006. Items included aspects related to IPV (physical/sexual/emotional), sociodemographic background, physical health, mental health (GHQ-12), social isolation, and social capital (i.e. social trust/participation). Results The response rate was 62.3% (n=804). Prevalence of lifetime reported IPV was 22.1%, with 20.5% by a previous partner and 6.7% by a current partner. Previous IPV exposure was significantly related to current IPV exposure, and all IPV exposure measures were significantly related to poor mental health. However, Thai women experiencing IPV by a current partner were more at risk for poor mental health than Thai women with previous or without any experience of IPV. Also, among all women exposed to IPV, those with trust in others and without exposure to social isolation seemed to have partial protection against the adverse mental health consequences associated with IPV. Conclusions Most Thai women had never been exposed to IPV, and after migrating to Sweden, women had lower IPV exposure than in Thailand. However, the increased risk for poor mental health among those Thai women exposed to IPV suggests the need for supportive measures and targeted interventions to prevent further injuries and adverse health consequences. Although poor mental health in Thai women represents an obstacle for integration, the potential resilience indicated in the group with high social trust and without exposure to social isolation suggests that such aspects be included in the program designed to facilitate

  18. Exposure chamber

    DOEpatents

    Moss, Owen R.; Briant, James K.

    1983-01-01

    An exposure chamber includes an imperforate casing having a fluid inlet at the top and an outlet at the bottom. A single vertical series of imperforate trays is provided. Each tray is spaced on all sides from the chamber walls. Baffles adjacent some of the trays restrict and direct the flow to give partial flow back and forth across the chambers and downward flow past the lowermost pan adjacent a central plane of the chamber.

  19. Children's exposure assessment: a review of factors influencing Children's exposure, and the data available to characterize and assess that exposure.

    PubMed Central

    Cohen Hubal, E A; Sheldon, L S; Burke, J M; McCurdy, T R; Berry, M R; Rigas, M L; Zartarian, V G; Freeman, N C

    2000-01-01

    We review the factors influencing children's exposure to environmental contaminants and the data available to characterize and assess that exposure. Children's activity pattern data requirements are demonstrated in the context of the algorithms used to estimate exposure by inhalation, dermal contact, and ingestion. Currently, data on children's exposures and activities are insufficient to adequately assess multimedia exposures to environmental contaminants. As a result, regulators use a series of default assumptions and exposure factors when conducting exposure assessments. Data to reduce uncertainty in the assumptions and exposure estimates are needed to ensure chemicals are regulated appropriately to protect children's health. To improve the database, advancement in the following general areas of research is required: identification of appropriate age/developmental benchmarks for categorizing children in exposure assessment; development and improvement of methods for monitoring children's exposures and activities; collection of activity pattern data for children (especially young children) required to assess exposure by all routes; collection of data on concentrations of environmental contaminants, biomarkers, and transfer coefficients that can be used as inputs to aggregate exposure models. PMID:10856019

  20. 30 CFR 62.130 - Permissible exposure level.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Permissible exposure level. 62.130 Section 62... REGULATIONS OCCUPATIONAL NOISE EXPOSURE § 62.130 Permissible exposure level. (a) The mine operator must assure that no miner is exposed during any work shift to noise that exceeds the permissible exposure level....

  1. 12 CFR 217.33 - Off-balance sheet exposures.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Off-balance sheet exposures. 217.33 Section 217... for General Credit Risk § 217.33 Off-balance sheet exposures. (a) General. (1) A Board-regulated institution must calculate the exposure amount of an off-balance sheet exposure using the credit...

  2. 30 CFR 62.110 - Noise exposure assessment.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Noise exposure assessment. 62.110 Section 62... REGULATIONS OCCUPATIONAL NOISE EXPOSURE § 62.110 Noise exposure assessment. (a) The mine operator must establish a system of monitoring that evaluates each miner's noise exposure sufficiently to...

  3. 30 CFR 62.110 - Noise exposure assessment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Noise exposure assessment. 62.110 Section 62... REGULATIONS OCCUPATIONAL NOISE EXPOSURE § 62.110 Noise exposure assessment. (a) The mine operator must establish a system of monitoring that evaluates each miner's noise exposure sufficiently to...

  4. 30 CFR 62.110 - Noise exposure assessment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Noise exposure assessment. 62.110 Section 62... REGULATIONS OCCUPATIONAL NOISE EXPOSURE § 62.110 Noise exposure assessment. (a) The mine operator must establish a system of monitoring that evaluates each miner's noise exposure sufficiently to...

  5. 30 CFR 62.110 - Noise exposure assessment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Noise exposure assessment. 62.110 Section 62... REGULATIONS OCCUPATIONAL NOISE EXPOSURE § 62.110 Noise exposure assessment. (a) The mine operator must establish a system of monitoring that evaluates each miner's noise exposure sufficiently to...

  6. Do the Mentally Retarded Have Poor Memory?

    ERIC Educational Resources Information Center

    Ellis, Norman R.

    1978-01-01

    A reevaluation of a number of experiments suggests that normal and retarded persons differ on short-term memory tasks from the time of initial stimulus exposure. The hypothesis that memory differences are due to differential encoding as a result of more adequate rehearsal by the normal subjects is unacceptable. (Author/BW)

  7. Molybdenum Abundances in Metal-Poor Stars

    NASA Astrophysics Data System (ADS)

    Peterson, R. C.

    2012-08-01

    Peterson (2011) has analyzed HST spectra near 2000Å of five metal-poor turnoff stars with mild enhancements of heavy r-process elements. Two stars, HD 94028 and HD 160617, are unique in showing an extreme overabundance of the light trans-ironic element molybdenum (Z = 42), but less extreme enhancements of Zr (Z = 40) and Ru (Z = 44). Of several nucleosynthesis scenarios that can produce nuclei in this mass range in the oldest stars, a high-entropy wind (HEW) acting in a core-collapse supernova seems uniquely capable of a high overproduction confined to a narrow mass range. That this unusual elemental distribution is achieved only under very limited physical conditions suggests that very few individual nucleosynthesis events were responsible for the synthesis of the light trans-ironic elements in these stars, even though both are only moderately metal-poor.

  8. Going Global, for Rich and Poor

    ERIC Educational Resources Information Center

    Mathews, Jay; Mathews, Linda

    2012-01-01

    International Baccalaureate (IB) programs are turning up in a diverse mix of school districts, an attempt to add rigor and depth. For rich and for poor, for big schools and small ones, IB has become a way to add rigor and depth to public school curricula. But each school district has adapted IB for its own needs. Some use it in all schools for all…

  9. [Skin problems associated with poor living conditions].

    PubMed

    Moretti, Francesco; Dory, Élodie; Favrat, Bernard; Winterton, Nina; Berger, Jérôme; Bodenmann, Patrick

    2015-11-25

    People living in poor conditions are at high risk of developing different medical diseases of which dermatological diseases are very common. We present 4 clinical cases of skin diseases, which are the most prevalent amongst the majority of socially and economically vulnerable patients. Early diagnosis and appropriate treatment are of paramount importance, in order to avoid their spread in close- knit communities where these patients often live. PMID:26742355

  10. Prenatal cigarette exposure and infant learning stimulation as predictors of cognitive control in childhood.

    PubMed

    Mezzacappa, Enrico; Buckner, John C; Earls, Felton

    2011-07-01

    Prenatal exposures to neurotoxins and postnatal parenting practices have been shown to independently predict variations in the cognitive development and emotional-behavioral well-being of infants and children. We examined the independent contributions of prenatal cigarette exposure and infant learning stimulation, as well as their inter-relationships in predicting variations in the proficiency of executive attention, a core element of cognitive control and self-regulation. Participants were an ethnic-racially, socio-economically diverse sample of 249 children followed from birth in the Project on Human Development in Chicago Neighborhoods. We obtained histories of prenatal exposure to alcohol, cigarettes, and other drugs, and we assessed socio-economic status and learning stimulation during a home visit when the participants were infants. In childhood we utilized the Attention Networks Test to assess the proficiency of executive attention during two home visits, one year apart. Accounting for age, SES, prenatal alcohol exposure, and baseline performance, we found that prenatal cigarette exposure impaired the speed of executive attention. Infant learning stimulation mitigated these effects, and predicted better accuracy of executive attention as well, suggestive of both protective and health promoting effects. Effect sizes for these relations, whether examined independently or by their inter-relationships, were comparable to if not greater in magnitude than the effects of age on speed and accuracy, highlighting the importance of these very early experiences in shaping the proficiency of self-regulation. Since executive attention is central to cognitive control and self-regulation, previously described relations between prenatal cigarette exposure, parenting practices, and some forms of childhood psychopathology may be contingent on how early learning stimulation contributes to the proficiency of executive attention through direct and indirect effects. Furthermore

  11. Ozone exposure: a case report and discussion.

    PubMed

    Parks, S; Paul, D W

    2000-02-01

    A 45-year-old man working with ozone presents with evidence of sinusitis, mucus membrane irritation, sleep disturbance and shortness of breath. Naturally occurring or manmade, ozone may damage pulmonary alveolar type I cells at significant exposure levels. EPA and OSHA regulate exposure concentrations. Studies show dose responses with exposures. Supporting epidemiological studies are reviewed briefly. Limiting potential for excess exposure is key to prevention. Recognition of ozone as a potential exposure in the Oklahoma workplace is key to symptom management. PMID:10692811

  12. Criminal exposure.

    PubMed

    1999-09-01

    In August, an HIV-positive man plead guilty to sexually assaulting a 14-year-old boy. The sleeping boy awoke to find [name removed] sexually assaulting him, while watching a pornographic video. [Name removed] plead guilty to the assault with intent to rape a child. In addition, [name removed] received three counts of indecent assault and battery on a child, and exposure of pornographic material to a minor. [Name removed] will remain on probation for five years, although the prosecution had recommended sentencing [name removed] to four or five years in prison. The boy continues to be tested for HIV. PMID:11366904

  13. Trends of Pesticide Exposure and Related Cases in the Philippines

    PubMed Central

    Lu, Jinky Leilanie; Cosca, Katherine Z.; Del mundo, Jocelyn

    2010-01-01

    The study aims to provide a comprehensive trend of pesticide poisoning cases in the Philippines as well as pesticide exposures, and risk factors related to the adverse effects of pesticide. Records were gathered from the National Poison Control and Management Center (NPCMC), the Philippine General Hospital, De La Salle Medical Center, and other hospitals, and reviewed research studies conducted in the Philippines. Based on hospital surveys, the number of pesticide cases as well as mortality trends have been increasing. Studies from 2006 to 2010 showed that human health especially those of the farmers is at risk due to pesticide exposure. Illnesses and symptoms such as headache, skin abnormalities, fatigue, fever, and weaknesses were the common health complaints experienced by the farmers as reported in the research studies. Moreover, the studies showed risk factors to pesticide exposure, work practices, and pesticide residues in environmental media that could be contributory to pesticide poisoning cases. Government agencies should intensify their surveillance and regulation on both household and agricultural pesticides. The state of pesticide-related illnesses mirrors the poor safety practices among farmers as well as lack of necessary supervision from the government agencies. PMID:25649374

  14. Medical graduates' knowledge of bloodborne viruses and occupational exposures.

    PubMed

    Koehler, Nicole; Vujovic, Olga; Dendle, Claire; McMenamin, Christine

    2014-02-01

    A survey of medical graduates commencing employment as junior doctors was performed to investigate knowledge of bloodborne viruses and occupational exposure management, coupled with their experience of occupational exposures. There was a mismatch between general knowledge (excellent) and knowledge of postexposure management (poor), and graduates had commonly experienced an occupational exposure and not reported it. The knowledge deficit regarding postexposure management and history of poor practice (ie, nonreporting) following an exposure implies that the transition period from student to junior doctor may be associated with increased occupational health and safety risk. PMID:24360355

  15. The landless poor--India's growing problem.

    PubMed

    Baidya, K N

    1985-01-01

    The bulk of poverty in India is found among those with no land or insufficient land with which to feed themselves. This predicament is a result of both population growth and the failure of the government to create sufficient employment opportunities in rural areas. India's inheritance custom, which calls for a sharing of property among a deceased's heirs, has fragmented farms into ever smaller holdings. The sharecropping system has created obstacles against participation of the rural masses in the development effort. The failure of agrarian reform efforts in India is attributed to the resistance of the powerful land-owning interests, supported by small landowners. Industrialization has not provided employment for the many rural unemployed who drift to the cities. It is not the lack of agricultural investment per se that is the source of the problem of the landless poor. Rather, social and political issues are involved. Large farms tend to obtain whatever aid is available for rural development. The increased use of electrification and mechanization has reduced the amount of employment available for landless workers. Half of India's arable land remains in the hands of 7% of the big land-holders. Thus, the gap between the haves and the have-nots has actually increased as a result of agricultural development. Food production has increased, but the ability of the poor masses to purchase food has decreased. As long as they are weak economically, the poor are likely to remain weak politically. Thus, there is a need for both economic and political reform. Resources must be massively diverted for the benefit of the rural sector, and power must be developed within democratic organizations at the rural level. The consequences of such change may be unacceptable to the elite classes who control the state apparatus and have the power to eradicate poverty and reduce inequality, however. PMID:12266988

  16. Poor mental health status and aggression are associated with poor driving behavior among male traffic offenders

    PubMed Central

    Abdoli, Nasrin; Farnia, Vahid; Delavar, Ali; Esmaeili, Alirez; Dortaj, Fariborz; Farrokhi, Noorali; Karami, Majid; Shakeri, Jalal; Holsboer-Trachsler, Edith; Brand, Serge

    2015-01-01

    Background In Iran, traffic accidents and deaths from traffic accidents are among the highest in the world, and generally driver behavior rather than either technical failures or environmental conditions are responsible for traffic accidents. In the present study, we explored the extent to which aggressive traits, health status, and sociodemographic variables explain driving behavior among Iranian male traffic offenders. Method A total of 443 male driving offenders (mean age: M =31.40 years, standard deviation =9.56) from Kermanshah (Iran) took part in the study. Participants completed a questionnaire booklet covering sociodemographic variables, traits of aggression, health status, and driving behavior. Results Poor health status, such as symptoms of depression, anxiety, insomnia, and social dysfunction, and also higher levels of trait aggression explained poor driving behavior. Multiple regressions indicated that poor health status, but not aggression, independently predicted poor driving behavior. Conclusion Results suggest that health status concerns are associated with poor driving behavior. Prevention and intervention might therefore focus on drivers reporting poor mental health status. PMID:26316753

  17. Asthma Care in Resource-Poor Settings

    PubMed Central

    2011-01-01

    Asthma prevalence in low-to middle-income countries is at least the same or higher than in rich countries, but with increased severity. Lack of control in these settings is due to various factors such as low accessibility to effective medications, multiple and uncoordinated weak infrastructures of medical services for the management of chronic diseases such as asthma, poor compliance with prescribed therapy, lack of asthma education, and social and cultural factors. There is an urgent requirement for the implementation of better ways to treat asthma in underserved populations, enhancing the access to preventive medications and educational approaches with modern technological methods. PMID:23282401

  18. DOE 2012 occupational radiation exposure

    SciTech Connect

    none,

    2013-10-01

    The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2012 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past 5-year period, the occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site.

  19. DOE 2011 occupational radiation exposure

    SciTech Connect

    none,

    2012-12-01

    The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2011 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past five years.

  20. Poor Sleep Is Related to Lower Emotional Competence Among Adolescents.

    PubMed

    Brand, Serge; Kirov, Roumen; Kalak, Nadeem; Gerber, Markus; Schmidt, Norman B; Lemola, Sakari; Correll, Christoph U; Holsboer-Trachsler, Edith

    2016-01-01

    The aim of the present study was to explore the association between subjective insomnia and self-reported emotional competence in areas such as regulating and perceiving one's own emotions and empathy, in a sample of adolescents. Gender differences were also explored. 366 adolescents in 10th to 12th grade (mean age: M = 16.9 years) took part in this cross-sectional study. They completed questionnaires related to emotional competencies, empathy, and sleep. Higher scores for insomnia were associated with lower scores for some aspects of emotional competence and empathy. Compared to males, females generally had higher scores for emotional competence. Poor sleep as subjectively experienced among adolescents is associated with specific impairments in emotional competence and empathy. Gender-related patterns were also observed. PMID:26507446

  1. Neurological and developmental approaches to poor pitch perception and production

    PubMed Central

    Loui, Psyche; Demorest, Steven M.; Pfordresher, Peter Q.; Iyer, Janani

    2014-01-01

    Whereas much of research in music and neuroscience is aimed at understanding the mechanisms by which the human brain facilitates music, emerging interest in the neuromusic community aims to translate basic music research into clinical and educational applications. In the present workshop, we explore the problems of poor pitch perception and production from both neurological and developmental/educational perspectives. We begin by reviewing previous and novel findings on the neural regulation of pitch perception and production. We then discuss issues in measuring singing accuracy consistently between the laboratory and educational settings. We review the Seattle Singing Accuracy Protocol—a new assessment tool that we hope can be adopted by cognitive psychologists as well as music educators—and we conclude with some suggestions that the present interdisciplinary approach might offer for future research. PMID:25773643

  2. Neurological and developmental approaches to poor pitch perception and production.

    PubMed

    Loui, Psyche; Demorest, Steven M; Pfordresher, Peter Q; Iyer, Janani

    2015-03-01

    Whereas much of research in music and neuroscience is aimed at understanding the mechanisms by which the human brain facilitates music, emerging interest in the neuromusic community aims to translate basic music research into clinical and educational applications. In the present paper, we explore the problems of poor pitch perception and production from both neurological and developmental/educational perspectives. We begin by reviewing previous and novel findings on the neural regulation of pitch perception and production. We then discuss issues in measuring singing accuracy consistently between the laboratory and educational settings. We review the Seattle Singing Accuracy Protocol--a new assessment tool that we hope can be adopted by cognitive psychologists as well as music educators-and we conclude with some suggestions that the present interdisciplinary approach might offer for future research. PMID:25773643

  3. Relationship between oral poor hygiene and broken teeth with oral tongue squamous cell carcinoma.

    PubMed

    Behnoud, Fatholah; Torabian, Saadat; Zargaran, Maasoumeh

    2011-01-01

    Previous studies on etiology of squamous cell carcinoma (SCC) of the tongue have reported results with respect to long term exposure to cigarette smoking and alcohol abuse. The aim of this study was to investigate risk factors for SCC of the tongue in a set of patients with minimum exposure to cigarette smoking and alcohol. Sixty four cases with diagnosis of oral tongue SCC were reviewed in this study. The patients underwent surgical management at the educational and therapeutic centers, Imam and Buali Hospitals (Hamedan, Iran) between the dates of January 1990 and December 2006. Eighty five percent of patients were older than 40 years of age. Most of patients had poor oral hygiene, dental decay and halitosis. It appears that poor oral hygiene and nutritional deficiency can be considered as risk factors for the SCC of the tongue in west of Iran. PMID:21681703

  4. Primary Hepatic Carcinoid Tumor with Poor Outcome.

    PubMed

    Parkash, Om; Ayub, Adil; Naeem, Buria; Najam, Sehrish; Ahmed, Zubair; Jafri, Wasim; Hamid, Saeed

    2016-03-01

    Primary Hepatic Carcinoid Tumor (PHCT) represents an extremely rare clinical entity with only a few cases reported to date. These tumors are rarely associated with metastasis and surgical resection is usually curative. Herein, we report two cases of PHCT associated with poor outcomes due to late diagnosis. Both cases presented late with non-specific symptoms. One patient presented after a 2-week history of symptoms and the second case had a longstanding two years symptomatic interval during which he remained undiagnosed and not properly worked up. Both these cases were diagnosed with hepatic carcinoid tumor, which originates from neuroendocrine cells. Case 1 opted for palliative care and expired in one month’s time. Surgical resection was advised to the second case, but he left against medical advice. PMID:26975959

  5. Direct multiangle solution for poorly stratified atmospheres.

    PubMed

    Kovalev, Vladimir; Wold, Cyle; Petkov, Alexander; Hao, Wei Min

    2012-09-01

    The direct multiangle solution is considered, which allows improving the scanning lidar-data-inversion accuracy when the requirement of the horizontally stratified atmosphere is poorly met. The signal measured at zenith or close to zenith is used as a core source for extracting optical characteristics of the atmospheric aerosol loading. The multiangle signals are used as auxiliary data to extract the vertical transmittance profile from the zenith signal. Details of the retrieval methodology are considered that eliminate, or at least soften, some specific ambiguities in the multiangle measurements in horizontally heterogeneous atmospheres. Simulated and experimental elastic lidar data are presented that illustrate the essentials of the data-processing technique. Finally, the prospects of the utilization of high-spectral-resolution lidar in the multiangle mode are discussed. PMID:22945162

  6. Poor-data and data-poor species stock assessment using a Bayesian hierarchical approach.

    PubMed

    Jiao, Yan; Cortés, Enric; Andrews, Kate; Guo, Feng

    2011-10-01

    Appropriate inference for stocks or species with low-quality data (poor data) or limited data (data poor) is extremely important. Hierarchical Bayesian methods are especially applicable to small-area, small-sample-size estimation problems because they allow poor-data species to borrow strength from species with good-quality data. We used a hammerhead shark complex as an example to investigate the advantages of using hierarchical Bayesian models in assessing the status of poor-data and data-poor exploited species. The hammerhead shark complex (Sphyrna spp.) along the Atlantic and Gulf of Mexico coasts of the United States is composed of three species: the scalloped hammerhead (S. lewini), the great hammerhead (S. mokarran), and the smooth hammerhead (S. zygaena) sharks. The scalloped hammerhead comprises 70-80% of the catch and has catch and relative abundance data of good quality, whereas great and smooth hammerheads have relative abundance indices that are both limited and of low quality presumably because of low stock density and limited sampling. Four hierarchical Bayesian state-space surplus production models were developed to simulate variability in population growth rates, carrying capacity, and catchability of the species. The results from the hierarchical Bayesian models were considerably more robust than those of the nonhierarchical models. The hierarchical Bayesian approach represents an intermediate strategy between traditional models that assume different population parameters for each species and those that assume all species share identical parameters. Use of the hierarchical Bayesian approach is suggested for future hammerhead shark stock assessments and for modeling fish complexes with species-specific data, because the poor-data species can borrow strength from the species with good data, making the estimation more stable and robust. PMID:22073653

  7. Exposure chamber

    DOEpatents

    Moss, Owen R.

    1980-01-01

    A chamber for exposing animals, plants, or materials to air containing gases or aerosols is so constructed that catch pans for animal excrement, for example, serve to aid the uniform distribution of air throughout the chamber instead of constituting obstacles as has been the case in prior animal exposure chambers. The chamber comprises the usual imperforate top, bottom and side walls. Within the chamber, cages and their associated pans are arranged in two columns. The pans are spaced horizontally from the walls of the chamber in all directions. Corresponding pans of the two columns are also spaced horizontally from each other. Preferably the pans of one column are also spaced vertically from corresponding pans of the other column. Air is introduced into the top of the chamber and withdrawn from the bottom. The general flow of air is therefore vertical. The effect of the horizontal pans is based on the fact that a gas flowing past the edge of a flat plate that is perpendicular to the flow forms a wave on the upstream side of the plate. Air flows downwardly between the chamber walls and the outer edges of the pan. It also flows downwardly between the inner edges of the pans of the two columns. It has been found that when the air carries aerosol particles, these particles are substantially uniformly distributed throughout the chamber.

  8. A global perspective on the influence of environmental exposures on the nervous system.

    PubMed

    Tshala-Katumbay, Desire; Mwanza, Jean-Claude; Rohlman, Diane S; Maestre, Gladys; Oriá, Reinaldo B

    2015-11-19

    Economic transitions in the era of globalization warrant a fresh look at the neurological risks associated with environmental change. These are driven by industrial expansion, transfer and mobility of goods, climate change and population growth. In these contexts, risk of infectious and non-infectious diseases are shared across geographical boundaries. In low- and middle-income countries, the risk of environmentally mediated brain disease is augmented several fold by lack of infrastructure, poor health and safety regulations, and limited measures for environmental protection. Neurological disorders may occur as a result of direct exposure to chemical and/or non-chemical stressors, including but not limited to, ultrafine particulate matters. Individual susceptibilities to exposure-related diseases are modified by genetic, epigenetic and metagenomic factors. The existence of several uniquely exposed populations, including those in the areas surrounding the Niger Delta or north western Amazon oil operations; those working in poorly regulated environments, such as artisanal mining industries; or those, mostly in sub-Saharan Africa, relying on cassava as a staple food, offers invaluable opportunities to advance the current understanding of brain responses to environmental challenges. Increased awareness of the brain disorders that are prevalent in low- and middle-income countries and investments in capacity for further environmental health-related research are positive steps towards improving human health. PMID:26580326

  9. The Affordable Housing Crisis: Residential Mobility of Poor Families and School Mobility of Poor Children.

    ERIC Educational Resources Information Center

    Crowley, Sheila

    2003-01-01

    Helping poor families increase their residential stability can have direct bearing on school stability and student academic achievement. Discusses the role of housing in child and family wellbeing; residential mobility and school performance; residential mobility and housing problems; housing affordability; (federal housing policy); homeownership;…

  10. Kinematics of AWM and MKW Poor Clusters

    NASA Astrophysics Data System (ADS)

    Koranyi, Daniel M.; Geller, Margaret J.

    2002-01-01

    We have measured 1365 redshifts to a limiting magnitude of R~15.5 in 15 AWM/MKW clusters and have collected another 203 from the literature in MKW 4s, MKW 2, and MKW 2s. In AWM 7 we have extended the redshift sample to R~18 in the cluster center. We have identified 704 cluster members in 17 clusters; 201 are newly identified. We summarize the kinematics and distributions of the cluster galaxies and provide an initial discussion of substructure, mass and luminosity segregation, spectral segregation, velocity-dispersion profiles, and the relation of the central galaxy to global cluster properties. We compute optical mass estimates, which we compare with X-ray mass determinations from the literature. The clusters are in a variety of dynamical states, reflected in the three classes of behavior of the velocity-dispersion profile in the core: rising, falling, or flat/ambiguous. The velocity dispersion of the emission-line galaxy population significantly exceeds that of the absorption-line galaxies in almost all of the clusters, and the presence of emission-line galaxies at small projected radii suggests continuing infall of galaxies onto the clusters. The presence of a cD galaxy does not constrain the global cluster properties; these clusters are similar to other poor clusters that contain no cD. We use the similarity of the velocity-dispersion profiles at small radii and the cD-like galaxies' internal velocity dispersions to argue that cD formation is a local phenomenon. Our sample establishes an empirical observational baseline of poor clusters for comparison with simulations of similar systems. Observations reported in this paper were obtained at the Multiple Mirror Telescope Observatory, a facility operated jointly by the University of Arizona and the Smithsonian Institution; at the Whipple Observatory, a facility operated jointly by the Smithsonian Astrophysical Observatory and Harvard University; and at the WIYN Observatory, a joint facility of the University of

  11. Environmental Source of Arsenic Exposure

    PubMed Central

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-01-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made. PMID:25284196

  12. Poorly Understood Aspects of Striated Muscle Contraction

    PubMed Central

    Månsson, Alf

    2015-01-01

    Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs. PMID:25961006

  13. Toward ab initio extremely metal poor stars

    NASA Astrophysics Data System (ADS)

    Ritter, Jeremy S.; Safranek-Shrader, Chalence; Milosavljević, Miloš; Bromm, Volker

    2016-09-01

    Extremely metal poor stars have been the focus of much recent attention owing to the expectation that their chemical abundances can shed light on the metal and dust yields of the earliest supernovae. We present our most realistic simulation to date of the astrophysical pathway to the first metal enriched stars. We simulate the radiative and supernova hydrodynamic feedback of a 60 M⊙ Population III star starting from cosmological initial conditions realizing Gaussian density fluctuations. We follow the gravitational hydrodynamics of the supernova remnant at high spatial resolution through its freely-expanding, adiabatic, and radiative phases, until gas, now metal-enriched, has resumed runaway gravitational collapse. Our findings are surprising: while the Population III progenitor exploded with a low energy of 1051 erg and injected an ample metal mass of 6 M⊙, the first cloud to collapse after the supernova explosion is a dense surviving primordial cloud on which the supernova blast wave deposited metals only superficially, in a thin, unresolved layer. The first metal-enriched stars can form at a very low metallicity, of only 2 - 5 × 10-4 Z⊙, and can inherit the parent cloud's highly elliptical, radially extended orbit in the dark matter gravitational potential.

  14. Deep Imaging of Extremely Metal-Poor Galaxies

    NASA Astrophysics Data System (ADS)

    Corbin, Michael

    2006-07-01

    Conflicting evidence exists regarding whether the most metal-poor and actively star-forming galaxies in the local universe such as I Zw 18 contain evolved stars. We propose to help settle this issue by obtaining deep ACS/HRC U, narrow-V, I, and H-alpha images of nine nearby {z < 0.01} extremely metal-poor {12 + O/H < 7.65} galaxies selected from the Sloan Digital Sky Survey. These objects are only marginally resolved from the ground and appear uniformly blue, strongly motivating HST imaging. The continuum images will establish: 1.} If underlying populations of evolved stars are present, by revealing the objects' colors on scales 10 pc, and 2.} The presence of any faint tidal features, dust lanes, and globular or super star clusters, all of which constrain the objects' evolutionary states. The H-alpha images, in combination with ground-based echelle spectroscopy, will reveal 1.} Whether the objects are producing "superwinds" that are depleting them of their metals; ground-based images of some of them indeed show large halos of ionized gas, and 2.} The correspondence of their nebular and stellar emission on scales of a few parsecs, which is important for understanding the "feedback" process by which supernovae and stellar winds regulate star formation. One of the sample objects, CGCG 269-049, lies only 2 Mpc away, allowing the detection of individual red giant stars in it if any are present. We have recently obtained Spitzer images and spectra of this galaxy to determine its dust content and star formation history, which will complement the proposed HST observations. [NOTE: THIS PROPOSAL WAS REDUCED TO FIVE ORBITS, AND ONLY ONE OF THE ORIGINAL TARGETS, CGCG 269-049, AFTER THE PHASE I REVIEW

  15. Efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide added to insulin therapy in poorly regulated patients with type 1 diabetes—a protocol for a randomised, double-blind, placebo-controlled study: The Lira-1 study

    PubMed Central

    Dejgaard, Thomas Fremming; Knop, Filip Krag; Tarnow, Lise; Frandsen, Christian Seerup; Hansen, Tanja Stenbæk; Almdal, Thomas; Holst, Jens Juul; Madsbad, Sten; Andersen, Henrik Ullits

    2015-01-01

    Introduction Intensive insulin therapy is recommended for the treatment of type 1 diabetes (T1D). Hypoglycaemia and weight gain are the common side effects of insulin treatment and may reduce compliance. In patients with insulin-treated type 2 diabetes, the addition of glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy has proven effective in reducing weight gain and insulin dose. The present publication describes a protocol for a study evaluating the efficacy and safety of adding a GLP-1RA to insulin treatment in overweight patients with T1D in a randomised, double-blinded, controlled design. Methods and analysis In total, 100 patients with type 1 diabetes, poor glycaemic control (glycated haemoglobin (HbA1c) >8%) and overweight (body mass index >25 kg/m2) will be randomised to either liraglutide 1.8 mg once daily or placebo as an add-on to intensive insulin therapy in this investigator initiated, double-blinded, placebo-controlled parallel study. The primary end point is glycaemic control as measured by changes in HbA1c. Secondary end points include changes in the insulin dose, hypoglyacemic events, body weight, lean body mass, fat mass, food preferences and adverse events. Glycaemic excursions, postprandial glucagon levels and gastric emptying rate during a standardised liquid meal test will also be studied. Ethics and dissemination The study is approved by the Danish Medicines Authority, the Regional Scientific-Ethical Committee of the Capital Region of Denmark and the Data Protection Agency. The study will be carried out under the surveillance and guidance of the good clinical practice (GCP) unit at Copenhagen University Hospital Bispebjerg in accordance with the ICH-GCP guidelines and the Helsinki Declaration. Trial registration number NCT01612468. PMID:25838513

  16. Prucalopride. In chronic constipation: poorly documented risks.

    PubMed

    2011-05-01

    Constipation is a frequent complaint, especially in women and the elderly. It is sometimes drug-induced, and is only occasionally secondary to a functional or organic disorder. The risks associated with constipation are often overestimated. Prucalopride, a 5-HT4 serotonin receptor agonist, chemically related to some neuroleptics, has been authorised in the European Union for symptomatic treatment of chronic constipation in women dissatisfied with laxatives. A combined analysis of 3 randomised double-blind trials in a total of 1999 patients (87.9% women) complaining of chronic constipation showed that about 36% of women considered it effective at a dose of 2 or 4 mg/day, versus 18% of women receiving placebo. Normal bowel movements resumed in respectively 23.6% and 24.7% of patients taking 2 and 4 mg/day prucalopride, versus 11.3% of patients on placebo (p < 0.001). No statistically significant difference was found between the 2 doses of prucalopride. Palpitations were more frequent in patients treated with prucalopride. The incidence of ischaemic cardiovascular events was 0.2% with prucalopride versus 0.1% with placebo. Increases in heart rate and blood pressure were observed in pigs and dogs treated with prucalopride. Prucalopride seems to increase prolactin levels. Tumours of the liver and thyroid were observed in rats. Prucalopride also carries a risk of poorly defined pharmacokinetic and pharmacodynamic interactions. Prucalopride may reduce the efficacy of oral contraceptives. Miscarriages were reported in clinical trials. Prucalopride should not be taken during pregnancy. In addition, all women of child-bearing age should use effective contraception while taking prucalopride. In practice, prucalopride should be avoided. It is better to focus on lifestyle and behavioural changes, and rational use of laxatives. PMID:21648173

  17. 30 CFR 62.110 - Noise exposure assessment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Noise exposure assessment. 62.110 Section 62.110 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR UNIFORM MINE HEALTH REGULATIONS OCCUPATIONAL NOISE EXPOSURE § 62.110 Noise exposure assessment. (a) The mine operator must establish a system of monitoring that...

  18. Environmental exposures, socioeconomics, disparities, and the kidneys.

    PubMed

    Said, Sarmad; Hernandez, German T

    2015-01-01

    Kidney disease disproportionately affects racial and ethnic minority populations, the poor, and the socially disadvantaged. The excess risk of kidney disease among minority and disadvantaged populations can only be partially explained by an excess of diabetes, hypertension, and poor access to preventive care. Disparities in the environmental exposure to nephrotoxicants have been documented in minority and disadvantaged populations and may explain some of the excess risk of kidney disease. High-level environmental and occupational exposure to lead, cadmium, and mercury are known to cause specific nephropathies. However, there is growing evidence that low-level exposures to heavy metals may contribute to the development of CKD and its progression. In this article, we summarize the excess risk of environmental exposures among minority and disadvantaged populations. We also review the epidemiologic and clinical data linking low-level environmental exposure to lead, cadmium, and mercury to CKD and its progression. Finally, we briefly describe Mesoamerican nephropathy, an epidemic of CKD affecting young men in Central America, which may have occupational and environmental exposures contributing to its development. PMID:25573511

  19. Childhood Absence Epilepsy: Poor Attention Is More Than Seizures

    MedlinePlus

    ... Spencer, MD Steven Karceski, MD Childhood absence epilepsy Poor attention is more than seizures Liu Lin Thio, ... of this article is prohibited. Childhood absence epilepsy: Poor attention is more than seizures Liu Lin Thio ...

  20. Very Early Language Skills of Fifth-Grade Poor Comprehenders

    PubMed Central

    Justice, Laura; Mashburn, Andrew; Petscher, Yaacov

    2015-01-01

    This study tested the theory that future poor comprehenders would show modest but pervasive deficits in both language comprehension and production during early childhood as compared with future poor decoders and typical readers. Using an existing database (NICHD ECCRN), fifth-grade students were identified as having poor comprehension skills (n = 516), poor decoding skills (n = 511) or typical reading skills (n = 535) based on standardized assessments of word recognition and reading comprehension. Language comprehension and production during the toddler and preschool years were retrospectively compared across these subgroups. Compared with future typical readers and poor decoders, poor comprehenders had the lowest abilities on language assessments at 15, 24, 36 and 54 months. For nearly all contrasts, the difference between poor comprehenders and the other groups of readers exceeded .5 standard deviation in magnitude, indicating that the early language skills of poor comprehenders exhibit appreciable lags. PMID:25620819

  1. ESTIMATED HOURLY PERSONAL EXPOSURES TO AMBIENT AND NON-AMBIENT PARTICULATE MATTER AMONG SENSITIVE POPULATIONS IN SEATTLE, WASHINGTON

    EPA Science Inventory

    Epidemiological studies of particulate matter (PM) routinely use concentrations measured with stationary outdoor monitors as surrogates for personal exposure. Despite the frequently reported poor correlations between ambient concentrations and total personal exposure, the epidemi...

  2. Exposure for ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats*

    EPA Science Inventory

    Rationale: Exposure to particulate matter is a risk factor for cardiopulmonary disease but the related molecular mechanisms are poorly understood. Previously we studied cardiovascular responses in healthy WKY rats following inhalation exposure to ultrafine carbon particles (UfCPs...

  3. Is public housing the cause of poor health or a safety net for the unhealthy poor?

    PubMed

    Ruel, Erin; Oakley, Deirdre; Wilson, G Elton; Maddox, Robert

    2010-09-01

    Research has shown that public housing residents have the worst health of any population in the USA. However, it is unclear what the cause of that poor health is among this population. The purpose of this paper is to investigate the association between public housing and health conditions: specifically, we ask if residents entered public housing already ill or if public housing may cause the poor health of its residents. The data used for this study come from the GSU Urban Health Initiative, which is a prospective, mixed-methods study of seven public housing communities earmarked for demolition and relocation (N = 385). We used the pre-relocation, baseline survey. We found that, while health was not the main reason residents gave for entering public housing, the majority of public housing residents entered public housing already ill. Substandard housing conditions, long tenure in public housing, and having had a worse living situation prior to public housing were not associated with an increased risk of a health condition diagnosed after entry into public housing. Our findings suggest that public housing may have provided a safety net for the very unhealthy poor. PMID:20585883

  4. Parietal function in good and poor readers

    PubMed Central

    Laycock, Robin; Crewther, Sheila G; Kiely, Patricia M; Crewther, David P

    2006-01-01

    Background While there are many psychophysical reports of impaired magnocellular pathway function in developmental dyslexia (DD), few have investigated parietal function, the major projection of this pathway, in good and poor readers closely matched for nonverbal intelligence. In view of new feedforward-feedback theories of visual processing, impaired magnocellular function raises the question of whether all visually-driven functions or only those associated with parietal cortex functions are equally impaired and if so, whether parietal performance is more closely related to general ability levels than reading ability. Methods Reading accuracy and performance on psychophysical tasks purported to selectively activate parietal cortex such as motion sensitivity, attentional tracking, and spatial localization was compared in 17 children with DD, 16 younger reading-age matched (RA) control children, and 46 good readers of similar chronological-age (CA) divided into CA-HighIQ and a CA-LowIQ matched to DD group nonverbal IQ. Results In the age-matched groups no significant differences were found between DD and CA controls on any of the tasks relating to parietal function, although performance of the DD group and their nonverbal IQ scores was always lower. As expected, CA and RA group comparisons indicated purported parietal functioning improves with age. No difference in performance was seen on any of the parietally driven tasks between the DD and age-nonverbal IQ matched groups, whereas performance differentiated the DD group from the age-matched, higher nonverbal IQ group on several such tasks. An unexpected statistical difference in performance between lower reading age (DD and RA children) and all higher reading age (CA) children was seen on a test of chromatic sensitivity, whereas when high and low nonverbal IQ normal readers were compared performance was not different Conclusion The results indicate that performance on purported parietal functions improves with age

  5. Very Early Language Skills of Fifth-Grade Poor Comprehenders

    ERIC Educational Resources Information Center

    Justice, Laura; Mashburn, Andrew; Petscher, Yaacov

    2013-01-01

    This study tested the theory that future poor comprehenders would show modest but pervasive deficits in both language comprehension and production during early childhood as compared with future poor decoders and typical readers. Using an existing database (NICHD ECCRN), fifth-grade students were identified as having poor comprehension skills…

  6. Laboring for Less: Working but Poor in Rural America.

    ERIC Educational Resources Information Center

    Shapiro, Isaac

    Most of the nonmetropolitan poor live in a household with at least one worker. In 1987, 70% of nonmetro poor family heads who were not ill, disabled, or retired worked for at least part of the year, and 24% worked full time, year-round. The employed proportion of the poor was significantly larger in nonmetro than metro areas. Despite a lengthy…

  7. Orthographic Processing and Visual Sequential Memory in Unexpectedly Poor Spellers

    ERIC Educational Resources Information Center

    Holmes, Virginia M.; Malone, Aisling M.; Redenbach, Holly

    2008-01-01

    Does unexpectedly poor spelling in adults result from inferior visual sequential memory? In one experiment, unexpectedly poor spellers performed significantly worse than better spellers in the immediate reproduction of sequences of visual symbols, but in a second experiment, the effect was not replicated. Poor spellers were also no worse at the…

  8. Maternal abuse history and self-regulation difficulties in preadolescence

    PubMed Central

    Delker, Brianna C.; Noll, Laura K.; Kim, Hyoun K.; Fisher, Philip A.

    2014-01-01

    Although poor parenting is known to be closely linked to self-regulation difficulties in early childhood, comparatively little is understood about the role of other risk factors in the early caregiving environment (such as a parent’s own experiences of childhood abuse) in developmental pathways of self-regulation into adolescence. Using a longitudinal design, this study aimed to examine how a mother’s history of abuse in childhood relates to her offspring’s self-regulation difficulties in preadolescence. Maternal controlling parenting and exposure to intimate partner aggression in the child’s first 24–36 months were examined as important early social and environmental influences that may explain the proposed connection between maternal abuse history and preadolescent self-regulation. An ethnically diverse sample of mothers (N = 488) who were identified as at-risk for child maltreatment was recruited at the time of their children’s birth. Mothers and their children were assessed annually from the child’s birth through 36 months, and at age 9–11 years. Structural equation modeling and bootstrap tests of indirect effects were conducted to address the study aims. Findings indicated that maternal abuse history indirectly predicted their children’s self-regulation difficulties in preadolescence mainly through maternal controlling parenting in early childhood, but not through maternal exposure to aggression by an intimate partner. Maternal history of childhood abuse and maternal controlling parenting in her child’s early life may have long-term developmental implications for child self-regulation. PMID:25459984

  9. Formaldehyde exposure and acute health effects study

    SciTech Connect

    Quackenboss, J.J.; Lebowitz, M.D.; Michaud, J.P.; Bronnimann, D. )

    1989-01-01

    To assess the effects of formaldehyde exposures on health, exposure groups were defined using baseline exposure and health questionnaires. Formaldehyde concentrations were poorly correlated with these exposure classifications, perhaps due to the time delay between classification and monitoring. The 151 households reported here had a mean HCHO concentration of 35 (S.E. 1.5 and median 30) {mu}g/m{sup 3}. Passive samplers prepared in our lab were calibrated in a chamber to derive an estimated sampling rate of 0.311 {mu}g/(mg {center dot} m{sup {minus}3} {center dot} hr). They were also compared to commercially available samplers inside of the homes, with a correlation coefficient of 0.896 and mean difference of 2.6 {mu}g/m{sup 3}. In this report of initial findings from an ongoing study, daily symptoms and peak expiratory flow measurements were compared with an HCHO exposure classification based on the median measured concentrations. None of the symptoms groups were related to HCHO exposure when controlling for age and sex. There was a significant relationship between HCHO exposure and variability in peak expiratory flows that was dependent on age group. It may be especially important to assess the variability in reactive individuals and children to determine the short-term effects of HCHO exposures and possible long-term consequences.

  10. Adult beetles compensate for poor larval food conditions.

    PubMed

    Müller, Thorben; Müller, Caroline

    2016-05-01

    Life history traits of herbivores are highly influenced by the quality of their hosts, i.e., the composition of primary and secondary plant metabolites. In holometabolous insects, larvae and adults may face different host plants, which differ in quality. It has been hypothesised that adult fitness is either highest when larval and adult environmental conditions match (environmental matching) or it may be mainly determined by optimal larval conditions (silver spoon effect). Alternatively, the adult stage may be most decisive for the actual fitness, independent of larval food exposure, due to adult compensation ability. To determine the influence of constant versus changing larval and adult host plant experiences on growth performance, fitness and feeding preferences, we carried out a match-mismatch experiment using the mustard leaf beetle, Phaedon cochleariae. Larvae and adults were either constantly reared on watercress (natural host) or cabbage (crop plant) or were switched after metamorphosis to the other host. Growth, reproductive traits and feeding preferences were determined repeatedly over lifetime and host plant quality traits analysed. Differences in the host quality led to differences in the development time and female reproduction. Egg numbers were significantly influenced by the host plant species experienced by the adults. Thus, adults were able to compensate for poor larval conditions. Likewise, the current host experience was most decisive for feeding preferences; in adult beetles a feeding preference was shaped regardless of the larval host plant. Larvae or adults reared on the more nutritious host, cabbage, showed a higher preference for this host. Hence, beetles most likely develop a preference when gaining a direct positive feedback in terms of an improved performance, whereby the current experience matters the most. Highly nutritious crop plants may be, in consequence, all the more exploited by potential pests that may show a high plasticity in

  11. Coping Strategies among Urban Poor: Evidence from Nairobi, Kenya

    PubMed Central

    Amendah, Djesika D.; Buigut, Steven; Mohamed, Shukri

    2014-01-01

    Aims In Kenya, it is estimated that 60 to 80% of urban residents live in slum or slum-like conditions. This study investigates expenditures patterns of slum dwellers in Nairobi, their coping strategies and the determinants of those coping strategies. Method We use a dataset from the Indicator Development for Surveillance of Urban Emergencies (IDSUE) research study conducted in four Nairobi slums from April 2012 to September 2012. The dataset includes information related to household livelihoods, earned incomes of household members, expenditures, shocks, and coping strategies. Results Food spending is the single most important component, accounting for 52% of total households' income and 42% of total expenditures. Households report a variety of coping strategies over the last four weeks preceding the interview. The most frequently used strategy is related to reduction in food consumption, followed by the use of credit, with 69% and 52% of households reporting using these strategies respectively. A substantial proportion of households also report removing children from school to manage spending shortfalls. Formal employment, owning a business, rent-free housing, belonging to the two top tiers of income brackets, and being a member of social safety net reduced the likelihood of using any coping strategy. Exposure to shocks and larger number of children under 15 years increased the probability of using a coping strategy. Policy Implications Policies that contain food price inflation, improve decent-paying job opportunities for the urban poor are likely to reduce the use of negative coping strategies by providing urban slum dwellers with steady and reliable sources of income. In addition, enhancing access to free primary schooling in the slums would help limit the need to use detrimental strategies like “removing” children from school. PMID:24427272

  12. Access to orphan drugs despite poor quality of clinical evidence

    PubMed Central

    Dupont, Alain G; Van Wilder, Philippe B

    2011-01-01

    AIM We analysed the Belgian reimbursement decisions of orphan drugs as compared with those of innovative drugs for more common but equally severe diseases, with special emphasis on the quality of clinical evidence. METHODS Using the National Health Insurance Agency administrative database, we evaluated all submitted orphan drug files between 2002 and 2007. A quality analysis of the clinical evidence in the orphan reimbursement files was performed. The evaluation reports of the French ‘Haute Autorité de Santé’, including the five-point scale parameter ‘Service Médical Rendu (SMR), were examined to compare disease severity. Chi-squared tests (at P < 0.05 significance level) were used to compare the outcome of the reimbursement decisions between orphan and non-orphan innovative medicines. RESULTS Twenty-five files of orphan drugs and 117 files of non-orphan drugs were evaluated. Twenty-two of 25 (88%) submissions of orphan drugs were granted reimbursement as opposed to 74 of the 117 (63%) non-orphan innovative medicines (P = 0.02). Only 52% of the 25 orphan drug files included a randomized controlled trial as opposed to 84% in a random control sample of 25 non-orphan innovative submissions (P < 0.01). The duration of drug exposure was in most cases far too short in relation to the natural history of the disease. CONCLUSIONS Orphan drug designation predicts reimbursement despite poor quality of clinical evidence. The evidence gap at market authorization should be reduced by post-marketing programmes, in which the centralized regulatory and the local reimbursement authorities collaborate in an efficient way across the European Union member states. PMID:21395641

  13. Medium wave exposure characterisation using exposure quotients.

    PubMed

    Paniagua, Jesús M; Rufo, Montaña; Jiménez, Antonio; Antolín, Alicia; Pinar, Iván

    2010-06-01

    One of the aspects considered in the International Commission on Non-Ionizing Radiation Protection guidelines is that, in situations of simultaneous exposure to fields of different frequencies, exposure quotients for thermal and electrical stimulation effects should be examined. The aim of the present work was to analyse the electromagnetic radiation levels and exposure quotients for exposure to multiple-frequency sources in the vicinity of medium wave radio broadcasting antennas. The measurements were made with a spectrum analyser and a monopole antenna. Kriging interpolation was used to prepare contour maps and to estimate the levels in the towns and villages of the zone. The results showed that the exposure quotient criterion based on electrical stimulation effects to be more stringent than those based on thermal effects or power density levels. Improvement of dosimetry evaluations requires the spectral components of the radiation to be quantified, followed by application of the criteria for exposure to multiple-frequency sources. PMID:20159912

  14. Combating poor-quality anti-malarial medicines: a call to action.

    PubMed

    Bassat, Quique; Tanner, Marcel; Guerin, Philippe J; Stricker, Kirstin; Hamed, Kamal

    2016-01-01

    The circulation of poor-quality medicines continues to undermine the fight against many life-threatening diseases. Anti-malarial medicines appear to have been particularly compromised and present a major public health threat in malaria-endemic countries, negatively affecting individuals and their communities. Concerted collaborative efforts are required from global, regional and national organizations, involving the public and private sectors, to address the problem. While many initiatives are underway, a number of unmet needs deserve urgent and increased multisector attention. At the global level, there is a need for an international public health legal framework or treaty on poor-quality medicines, with statutes suitable for integration into national laws. In addition, increased international efforts are required to strengthen the governance of global supply chains and enhance cooperation between national medicine regulation authorities and law enforcement bodies. Increased investment is needed in innovative technologies that will enable healthcare teams to detect poor-quality medicines at all levels of the supply chain. At the regional level, a number of initiatives would be beneficial-key areas are standardization, simplification, and reciprocal recognition of registration processes and development of quality control capacity in regional centres of excellence that are better aligned with public health needs; improved surveillance methods and creation of a framework for compulsory and transparent reporting of poor-quality medicines; additional support for national medicine regulation authorities and other national partner authorities; and an increase in support for regional laboratories to boost their capabilities in detecting poor-quality medicines. It is vital that all stakeholders involved in efforts against poor-quality anti-malarial medicines extend and strengthen their actions in these critical areas and thus effectively support global health development

  15. Self-Regulation and Mathematics Instruction

    ERIC Educational Resources Information Center

    Montague, Marjorie

    2007-01-01

    The purpose of this article is to provide an overview of research-based interventions that incorporate self-regulation strategies to improve mathematics performance of students with learning disabilities (LD). Self-regulation is a metacognitive function essential to academic success. Students with LD are notoriously poor at self-regulation and…

  16. Toxicogenomic and Phenotypic Analyses of Bisphenol-A Early-Life Exposure Toxicity in Zebrafish

    PubMed Central

    Lam, Siew Hong; Hlaing, Mya Myintzu; Zhang, Xiaoyan; Yan, Chuan; Duan, Zhenghua; Zhu, Lin; Ung, Choong Yong; Mathavan, Sinnakaruppan; Ong, Choon Nam; Gong, Zhiyuan

    2011-01-01

    Bisphenol-A is an important environmental contaminant due to the increased early-life exposure that may pose significant health-risks to various organisms including humans. This study aimed to use zebrafish as a toxicogenomic model to capture transcriptomic and phenotypic changes for inference of signaling pathways, biological processes, physiological systems and identify potential biomarker genes that are affected by early-life exposure to bisphenol-A. Phenotypic analysis using wild-type zebrafish larvae revealed BPA early-life exposure toxicity caused cardiac edema, cranio-facial abnormality, failure of swimbladder inflation and poor tactile response. Fluorescent imaging analysis using three transgenic lines revealed suppressed neuron branching from the spinal cord, abnormal development of neuromast cells, and suppressed vascularization in the abdominal region. Using knowledge-based data mining algorithms, transcriptome analysis suggests that several signaling pathways involving ephrin receptor, clathrin-mediated endocytosis, synaptic long-term potentiation, axonal guidance, vascular endothelial growth factor, integrin and tight junction were deregulated. Physiological systems with related disorders associated with the nervous, cardiovascular, skeletal-muscular, blood and reproductive systems were implicated, hence corroborated with the phenotypic analysis. Further analysis identified a common set of BPA-targeted genes and revealed a plausible mechanism involving disruption of endocrine-regulated genes and processes in known susceptible tissue-organs. The expression of 28 genes were validated in a separate experiment using quantitative real-time PCR and 6 genes, ncl1, apoeb, mdm1, mycl1b, sp4, U1SNRNPBP homolog, were found to be sensitive and robust biomarkers for BPA early-life exposure toxicity. The susceptibility of sp4 to BPA perturbation suggests its role in altering brain development, function and subsequently behavior observed in laboratory animals exposed

  17. Poor response to clopidogrel: current and future options for its management.

    PubMed

    Campo, Gianluca; Fileti, Luca; Valgimigli, Marco; Tebaldi, Matteo; Cangiano, Elisa; Cavazza, Caterina; Marchesini, Jlenia; Ferrari, Roberto

    2010-10-01

    Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes and/or undergoing percutaneous coronary interventions (PCI). Clopidogrel, a thienopyridine antiplatelet agent, has been used to prevent vascular complication in atherothrombotic patients, to prevent stent thrombosis in patients undergoing PCI, and in long term prevention of cardiovascular and cerebrovascular events. More than 40 million patients in the world receive clopidogrel but unfortunately about 20% of these are either non or poor responders. Several methods have been used to assess clopidogrel-induced antiplatelet effects. However, none of these tests have been fully standardized or fully agreed upon to measure clopidogrel responsiveness. Nevertheless, many studies using different techniques, platelet agonists and definitions, showed that patients with a poor response to clopidogrel have an increased risk of death, reinfarction and stent thrombosis. The mechanisms leading to poor responsiveness are not fully clarified and are likely multifactorial: genetic factors, accelerated platelet turnover, up-regulation of the P2Y(12) pathways, high baseline platelet reactivity, poor compliance, under-dosing and drug-drug interactions. The management of these patients is very difficult, but some evidence showed that a strategy of higher maintenance dose or switch to different thienopyridine (e.g. ticlopidine or prasugrel) or use of glycoprotein IIb/IIIa inhibitors during PCI may be helpful to overcome poor responsiveness and improve the long-term clinical outcome. This paper reviews the impact of clopidogrel poor responsiveness on clinical outcomes, the mechanisms leading to poor effect and the different assays to assess it. Finally, current and future options for its management is discussed. PMID:20157839

  18. OCCUPATIONAL EXPOSURE TO EXTERNAL RADIATION IN SWITZERLAND.

    PubMed

    Mayer, S; Baechler, S; Damet, J; Elmiger, R; Frei, D; Giannini, S; Leupin, A; Sarott, F; Schuh, R

    2016-09-01

    Individual monitoring for both external and internal exposures is well regulated in Switzerland. The article gives an overview on the occupational exposure to external radiation of workers based on the data collected in the Swiss national dose registry (NDR) in 2013. The NDR records the monthly doses of radiation workers since the introduction of ICRP 60 recommendations and is manifested in the Swiss ordinance since 1994. Annual dose limits for effective dose are typically exceeded once a year in Switzerland, mostly in medicine. The NDR is a useful optimisation tool to identify and characterise areas with the highest exposures. While exceeded dose limits were often related to accidental acute exposure in the past, they are now more related to continuous exposure during normal work, especially in medicine. PMID:27012882

  19. Understanding existing exposure situations.

    PubMed

    Lecomte, J-F

    2016-06-01

    International Commission on Radiological Protection (ICRP) Publication 103 removed the distinction between practices and interventions, and introduced three types of exposure situation: existing, planned, and emergency. It also emphasised the optimisation principle in connection with individual dose restrictions for all controllable exposure situations. Existing exposure situations are those resulting from sources, natural or man-made, that already exist when a decision on control has to be taken. They have common features to be taken into account when implementing general recommendations, such as: the source may be difficult to control; all exposures cannot be anticipated; protective actions can only be implemented after characterisation of the exposure situation; time may be needed to reduce exposure below the reference level; levels of exposure are highly dependent on individual behaviour and present a wide spread of individual dose distribution; exposures at work may be adventitious and not considered as occupational exposure; there is generally no potential for accident; many stakeholders have to be involved; and many factors need to be considered. ICRP is currently developing a series of reports related to the practical implementation of Publication 103 to various existing exposure situations, including exposure from radon, exposure from cosmic radiation in aviation, exposure from processes using naturally occurring radioactive material, and exposure from contaminated sites due to past activities. PMID:26975365

  20. DEMONSTRATION OF HUMAN EXPOSURE TOOLS

    EPA Science Inventory

    The Human Exposure and Atmospheric Sciences Division (HEASD) of the National Exposure Research Laboratory (NERL) conducts research on exposure measurements, human activity patterns, exposure and dose models, and cumulative exposures critical for the Agency to make scientificall...

  1. Affect labeling enhances exposure effectiveness for public speaking anxiety.

    PubMed

    Niles, Andrea N; Craske, Michelle G; Lieberman, Matthew D; Hur, Christopher

    2015-05-01

    Exposure is an effective treatment for anxiety but many patients do not respond fully. Affect labeling (labeling emotional experience) attenuates emotional responding. The current project examined whether affect labeling enhances exposure effectiveness in participants with public speaking anxiety. Participants were randomized to exposure with or without affect labeling. Physiological arousal and self-reported fear were assessed before and after exposure and compared between groups. Consistent with hypotheses, participants assigned to Affect Labeling, especially those who used more labels during exposure, showed greater reduction in physiological activation than Control participants. No effect was found for self-report measures. Also, greater emotion regulation deficits at baseline predicted more benefit in physiological arousal from exposure combined with affect labeling than exposure alone. The current research provides evidence that behavioral strategies that target prefrontal-amygdala circuitry can improve treatment effectiveness for anxiety and these effects are particularly pronounced for patients with the greatest deficits in emotion regulation. PMID:25795524

  2. DOE 2013 occupational radiation exposure

    SciTech Connect

    none,

    2014-11-01

    The Office of Analysis within the U.S. Department of Energy (DOE) Office of Environment, Health, Safety and Security (EHSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2013 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past five-year period, the occupational radiation exposure information has been analyzed in terms of aggregate data, dose to individuals, and dose by site.

  3. Mitochondrial Epigenetics and Environmental Exposure.

    PubMed

    Lambertini, Luca; Byun, Hyang-Min

    2016-09-01

    The rising toll of chronic and debilitating diseases brought about by the exposure to an ever expanding number of environmental pollutants and socio-economic factors is calling for action. The understanding of the molecular mechanisms behind the effects of environmental exposures can lead to the development of biomarkers that can support the public health fields of both early diagnosis and intervention to limit the burden of environmental diseases. The study of mitochondrial epigenetics carries high hopes to provide important biomarkers of exposure and disease. Mitochondria are in fact on the frontline of the cellular response to the environment. Modifications of the epigenetic factors regulating the mitochondrial activity are emerging as informative tools that can effectively report on the effects of the environment on the phenotype. Here, we will discuss the emerging field of mitochondrial epigenetics. This review describes the main epigenetic phenomena that modify the activity of the mitochondrial DNA including DNA methylation, long and short non-coding RNAs. We will discuss the unique pattern of mitochondrial DNA methylation, describe the challenges of correctly measuring it, and report on the existing studies that have analysed the correlation between environmental exposures and mitochondrial DNA methylation. Finally, we provide a brief account of the therapeutic approaches targeting mitochondria currently under consideration. PMID:27344144

  4. Kinematics and dynamics of the MKW/AWM poor clusters

    NASA Technical Reports Server (NTRS)

    Beers, Timothy C.; Kriessler, Jeffrey R.; Bird, Christina M.; Huchra, John P.

    1995-01-01

    We report 472 new redshifts for 416 galaxies in the regions of the 23 poor clusters of galaxies originally identified by Morgan, Kayser, and White (MKW), and Albert, White, and Morgan (AWM). Eighteen of the poor clusters now have 10 or more available redshifts within 1.5/h Mpc of the central galaxy; 11 clusters have at least 20 available redshifts. Based on the 21 clusters for which we have sufficient velocity information, the median velocity scale is 336 km/s, a factor of 2 smaller than found for rich clusters. Several of the poor clusters exhibit complex velocity distributions due to the presence of nearby clumps of galaxies. We check on the velocity of the dominant galaxy in each poor cluster relative to the remaining cluster members. Significantly high relative velocities of the dominant galaxy are found in only 4 of 21 poor clusters, 3 of which we suspect are due to contamination of the parent velocity distribution. Several statistical tests indicate that the D/cD galaxies are at the kinematic centers of the parent poor cluster velocity distributions. Mass-to-light ratios for 13 of the 15 poor clusters for which we have the required data are in the range 50 less than or = M/L(sub B(0)) less than or = 200 solar mass/solar luminosity. The complex nature of the regions surrounding many of the poor clusters suggests that these groupings may represent an early epoch of cluster formation. For example, the poor clusters MKW7 and MKWS are shown to be gravitationally bound and likely to merge to form a richer cluster within the next several Gyrs. Eight of the nine other poor clusters for which simple two-body dynamical models can be carried out are consistent with being bound to other clumps in their vicinity. Additional complex systems with more than two gravitationally bound clumps are observed among the poor clusters.

  5. Kinematics and dynamics of the MKW/AWM poor clusters

    NASA Astrophysics Data System (ADS)

    Beers, Timothy C.; Kriessler, Jeffrey R.; Bird, Christina M.; Huchra, John P.

    1995-03-01

    We report 472 new redshifts for 416 galaxies in the regions of the 23 poor clusters of galaxies originally identified by Morgan, Kayser, and White (MKW), and Albert, White, and Morgan (AWM). Eighteen of the poor clusters now have 10 or more available redshifts within 1.5/h Mpc of the central galaxy; 11 clusters have at least 20 available redshifts. Based on the 21 clusters for which we have sufficient velocity information, the median velocity scale is 336 km/s, a factor of 2 smaller than found for rich clusters. Several of the poor clusters exhibit complex velocity distributions due to the presence of nearby clumps of galaxies. We check on the velocity of the dominant galaxy in each poor cluster relative to the remaining cluster members. Significantly high relative velocities of the dominant galaxy are found in only 4 of 21 poor clusters, 3 of which we suspect are due to contamination of the parent velocity distribution. Several statistical tests indicate that the D/cD galaxies are at the kinematic centers of the parent poor cluster velocity distributions. Mass-to-light ratios for 13 of the 15 poor clusters for which we have the required data are in the range 50 less than or = M/LB(0) less than or = 200 solar mass/solar luminosity. The complex nature of the regions surrounding many of the poor clusters suggests that these groupings may represent an early epoch of cluster formation. For example, the poor clusters MKW7 and MKWS are shown to be gravitationally bound and likely to merge to form a richer cluster within the next several Gyrs. Eight of the nine other poor clusters for which simple two-body dynamical models can be carried out are consistent with being bound to other clumps in their vicinity. Additional complex systems with more than two gravitationally bound clumps are observed among the poor clusters.

  6. Particle exposures and infections

    EPA Science Inventory

    Particle exposures increase the risk for human infections. Particles can deposit in the nose, pharynx, larynx, trachea, bronchi, and distal lung and, accordingly, the respiratory tract is the system most frequently infected after such exposure; however, meningitis also occurs. Ci...

  7. EPIDEMIOLOGY AND EXPOSURE ASSESSMENT

    EPA Science Inventory

    Research collaborations between the National Health and Environmental Effects Research Laboratory (NHEERL) and the National Exposure Research Laboratory (NERL) centered on the development and application of exposure analysis tools in environmental epidemiology include the El Paso...

  8. CHAPTER ONE: EXPOSURE MEASUREMENTS.

    EPA Science Inventory

    Determining human exposure to suspended particualte concentrations requires measurements that quantify different particle properties in microenvironments where people live, work, and play. Particle mass, size, and chemical composition are important exposure variables, and these ...

  9. Integrated Exposure Assessment Monitoring.

    ERIC Educational Resources Information Center

    Behar, Joseph V.; And Others

    1979-01-01

    Integrated Exposure Assessment Monitoring is the coordination of environmental (air, water, land, and crops) monitoring networks to collect systematically pollutant exposure data for a specific receptor, usually man. (Author/BB)

  10. Are families poor because they are large or are they large because they are poor?

    PubMed

    Pernia, E M

    1982-01-01

    In the Philippines time allocation studies suggest that children cost considerable amounts of time and energy on the part of the mother and other siblings in addition to direct financial outlays which figure prominently. Yet, these costs seem to be compensated for by economic and noneconomic benefits. The time costs of children are moderated to the extent that mother's time has a low opportunity cost, given lack of marketable skills or sheer absence of employment opportunities. It is at the expense of investment in human capital (in terms of education and health) that economic benefits from child labor are forthcoming. As neither unemployment of the mother nor child labor is desirable, it would seem that economic benefits from children are expensive. The child's mental and physical development tends to be impaired due to deficient health, nutrition, and education inputs because family resources and parental care have to be spread so thinly among the many competing demands of the large family. Mother's health is negatively affected by frequent and closely spaced pregnancies, and she is effectively prevented from actual or potential participation in development. It is to these less immediate and not directly observable disadvantages of a large family that parents must be sensitized so that they will realize the need to limit family size. From the social perspective, the population program may be viewed as a strategy for human resource development. The challenge to policymakers has become formidable. Due to rapidly increasing population, the need to telescope the reduction of income inequality and poverty has become urgent. Continuing population growth tends to nullify whatever advances are made toward the distributional objective. Population and development policy needs to be directed to the poor in rural areas in general and more specifically to the rural poor in the backward regions of the Visayas, Bicol, Bocos, and Northern Mindanao. Given the extreme poverty of

  11. Queen pheromone regulates egg production in a termite.

    PubMed

    Yamamoto, Yuuka; Matsuura, Kenji

    2011-10-23

    In social insects, resource allocation is a key factor that influences colony survival and growth. Optimal allocation to queens and brood is essential for maximum colony productivity, requiring colony members to have information on the total reproductive power in colonies. However, the mechanisms regulating egg production relative to the current labour force for brood care remain poorly known. Recently, a volatile chemical was identified as a termite queen pheromone that inhibits the differentiation of new neotenic reproductives (secondary reproductives developed from nymphs or workers) in Reticulitermes speratus. The same volatile chemical is also emitted by eggs. This queen pheromone would therefore be expected to act as an honest message of the reproductive power about queens. In this study, we examined how the queen pheromone influences the reproductive rate of queens in R. speratus. We compared the number of eggs produced by each queen between groups with and without exposure to artificial queen pheromone. Exposure to the pheromone resulted in a significant decrease in egg production in both single-queen and multiple-queen groups. This is the first report supporting the role of queen pheromones as a signal regulating colony-level egg production, using synthetically derived compounds in a termite. PMID:21543395

  12. Benefits of Computer-Presented Speed Training for Poor Readers

    ERIC Educational Resources Information Center

    Irausquin, Rosemarie S.; Drent, Jeanine; Verhoeven, Ludo

    2005-01-01

    The effects of computer-presented automatization exercises in a group of 14 poor readers were assessed in comparison to a matched control group of 14 poor readers that received computer-presented exercises aimed at the use of context for word identification and comprehension. Training took place three sessions a week for 15 minutes per session and…

  13. Patterns of Risk: The Nutritional Status of the Rural Poor.

    ERIC Educational Resources Information Center

    Shotland, Jeffrey; Loonin, Deanne

    Nutrition and health are underlying influences to education performance. This report is a collection and analysis of data on nutrition and the rural poor in the United States. It presents an empirical assessment of critical nutritional and social-service problems experienced by the rural poor population. The first section of the report uses data…

  14. Semantic Priming Effects in Normal versus Poor Readers

    ERIC Educational Resources Information Center

    Assink, Egbert M. H.; Van Bergen, Floor; Van Teeseling, Heleen; Knuijt, Paul P. N. A.

    2004-01-01

    The authors studied sensitivity to semantic priming, as distinct from semantic judgment, in poor readers. Association strength (high vs. low semantic association) was manipulated factorially with semantic association type (categoric vs. thematic association). Participants were 11-year-old poor readers (n = 15) who were matched with a group of…

  15. RECREATION FOR THE RICH AND POOR, A CONTRAST.

    ERIC Educational Resources Information Center

    KRAUS, RICHARD G.

    THE DIVERGENCE BETWEEN THE LEISURE ACTIVITIES OF AFFLUENT AND POOR AMERICANS IS DISCUSSED. PARADOXICALLY, THOSE WITH THE GREATEST AMOUNT OF FREE TIME--THE POOR--HAVE THE LEAST MONEY WITH WHICH TO ENRICH THEIR LEISURE TIME. WHILE IT IS TRUE THAT AN EXTRAORDINARY VARIETY OF LEISURE ACTIVITIES ARE NOW AVAILABLE, ONLY THE MIDDLE AND UPPER CLASSES CAN…

  16. Unexpectedly Poor Spelling and Phonological-Processing Skill

    ERIC Educational Resources Information Center

    Holmes, Virginia M.; Quinn, Lisa

    2009-01-01

    This study investigated the phonological skills of university students who were unexpectedly poor spellers relative to their word reading accuracy. Compared with good spellers, unexpectedly poor spellers showed no deficits in phonological memory, selection of appropriate graphemes for phonemes in word misspellings and nonword spellings, and…

  17. Prevalence and Nature of Late-Emerging Poor Readers

    ERIC Educational Resources Information Center

    Catts, Hugh W.; Compton, Donald; Tomblin, J. Bruce; Bridges, Mindy Sittner

    2012-01-01

    Some children demonstrate adequate or better reading achievement in early school grades but fall significantly behind their peers in later grades. These children are often referred to as late-emerging poor readers. In this study, we investigated the prevalence and heterogeneity of these poor readers. We also examined the early language and…

  18. Distinguishing between Poor/Dysfunctional Parenting and Child Emotional Maltreatment

    ERIC Educational Resources Information Center

    Wolfe, David A.; McIsaac, Caroline

    2011-01-01

    Objective: This paper was intended to distinguish between poor parenting and child emotional maltreatment (CEM), to inform child welfare and public health policymakers of the need for differentiated responses. Methods: Scientific literature was integrated with current practice and assumptions relating to poor/dysfunctional parenting and child…

  19. Sustainable School Music for Poor, White, Rural Students

    ERIC Educational Resources Information Center

    Bates, Vincent C.

    2011-01-01

    "Poor white trash" is likely the most enduring and degrading in a long line of "stigmatypes"--"stigmatizing boundary terms that simultaneously denote and enact cultural and cognitive divides between in-groups and out-groups"--such as "redneck," "cracker," and "hillbilly." Some people apply these terms in reference to poor or working-class, usually…

  20. An Image Study on the Rich and Poor Perception

    ERIC Educational Resources Information Center

    Koçak, Recep

    2015-01-01

    The aim of this study is to project people's perceptions about the rich and poor. In this descriptive study, a questionnaire developed by the researcher and caricatures were used to collect data. The questionnaire composed of seven items including questions directed to adjectives related to the participants' perceptions about the rich and poor as…

  1. Rich Man, Poor Man: Developmental Differences in Attributions and Perceptions

    ERIC Educational Resources Information Center

    Sigelman, Carol K.

    2012-01-01

    In an examination guided by cognitive developmental and attribution theory of how explanations of wealth and poverty and perceptions of rich and poor people change with age and are interrelated, 6-, 10-, and 14-year-olds (N = 88) were asked for their causal attributions and trait judgments concerning a rich man and a poor man. First graders, like…

  2. Poor Kids in a Rich Nation: Eating the Seed Corn.

    ERIC Educational Resources Information Center

    Garrett, Patricia

    This paper examines the problem of having many poor children in the wealthy United States and the need to find answers to this problem. Despite much recent talk about "family values," the dominant U.S. ideology holds that family welfare is a private rather than a public responsibility. Poor children are seen as a special population that diverts…

  3. Mandated empowerment: handing antipoverty policy back to the poor?

    PubMed

    Banerjee, Abhijit V; Duflo, Esther

    2008-01-01

    The current trend in antipoverty policy emphasizes mandated empowerment: the poor are being handed the responsibility for making things better for themselves, largely without being asked whether this is what they want. Beneficiary control is now being built into public service delivery, while microcredit and small business promotion are seen as better ways to help the poor. The clear presumption is that the poor are both able and happy to exercise these new powers. This essay uses two examples to raise questions about these strategies. The first example is about entrepreneurship among the poor. Using data from a number of countries, we argue that there is no evidence that the median poor entrepreneur is trying his best to expand his existing businesses, even if we take into account the many constraints he faces. While many poor people own businesses, this seems to be more a survival strategy than something they want to do. The second example comes from an evaluation of a program in India that aims to involve poor rural parents in improving local public schools. The data suggest that despite being informed that they now have both the right to intervene in the school and access to funds for that purpose, and despite being made aware of how little the children were learning, parents opt to not get involved. Both examples raise concerns about committing ourselves entirely to antipoverty strategies that rely on the poor doing a lot of the work. PMID:18579890

  4. Poor Women Are Still Shut Out of Mainstream Psychology.

    ERIC Educational Resources Information Center

    Saris, Renee N.; Johnston-Robledo, Ingrid

    2000-01-01

    Followed up a 1993 study which concluded that poor and minority women were essentially shut out of mainstream psychological research and theory. Analysis of PsycLit abstracts from 1991-97 investigated whether significant change had occurred and noted the inclusion of poor women in research on sexuality and reproductive health. Results suggest that…

  5. Pathologizing the Language and Culture of Poor Children

    ERIC Educational Resources Information Center

    Dudley-Marling, Curt; Lucas, Krista

    2009-01-01

    There has been a resurgence of deficit discourses that implicate deficiencies in the language and culture of poor students as the cause of their academic failures. An influential study by Betty Hart and Todd Risley concludes that high levels of academic failure among poor children can be linked to the quantity and quality of language interactions…

  6. No Way Out: Working Poor Women in the United States.

    ERIC Educational Resources Information Center

    National Commission on Working Women, Washington, DC.

    This report examines the situation of the one-half of the nation's nine million working poor who are female. It begins by looking at just who the working poor are. Two areas of study are education levels and types of jobs. The discussion then shifts to minimum wage earners and their characteristics, the current status of the minimum wage, and the…

  7. Exposure assessment for chemical and physical agents.

    PubMed

    Moretto, Angelo

    2015-01-01

    Exposure assessment to either chemical or physical agents, as applicable, is a necessary step for both etiologic diagnosis of occupational disease and health surveillance of workers. The assessment can be carried out by measurements of concentrations in air of the substance by either fixed or personal samplers. The former give an indication of the general environment, the latter, applied near the mouth of the worker, provide personalized information. Dermal exposure (deposition) and absorption occur in the occupational setting, but their measurement is so complex that there are no routine methods and no exposure limits established. Oral exposure is accidental or associated with poor hygienic practices, is very difficult to assess, and there are no occupational exposure limits of oral intake. Also accidental injuries caused by needles or other sharp objects that might be contaminated by chemicals occur but exposure assessment in this condition is almost impossible. Exposure is also assessed by biologic monitoring that entails measurements of the substance and/or of its metabolite(s) in accessible fluids, generally urine, blood, or expired air. Biochemical changes, e.g., enzyme inhibition, associated with exposure are also measured. The results of these measurements are compared with existing limit values in order to conclude on the safety of the working conditions. Since the limit values are derived with the application of conservative assumptions, there are no fine lines between health and disease. Therefore, in the clinical setting values below the limit can be generally regarded as safe. Values above the limits should be considered in conjunction with all other information to judge on the likelihood that the disease under investigation may have been caused by exposure to the substance. PMID:26563782

  8. Opioid Antagonist Impedes Exposure.

    ERIC Educational Resources Information Center

    Merluzzi, Thomas V.; And Others

    1991-01-01

    Thirty spider-phobic adults underwent exposure to 17 phobic-related, graded performance tests. Fifteen subjects were assigned to naltrexone, an opioid antagonist, and 15 were assigned to placebo. Naltrexone had a significant effect on exposure, with naltrexone subjects taking significantly longer to complete first 10 steps of exposure and with…

  9. DIETARY EXPOSURE MEASUREMENTS

    EPA Science Inventory

    This research constitutes the MCEARD base dietary exposure research program and is conducted to complement the NERL total human exposure program. The research builds on previous work to reduce the level of uncertainty in exposure assessment by improving NERL's ability to evaluat...

  10. GUIDELINES FOR EXPOSURE ASSESSMENT

    EPA Science Inventory

    The Guidelines for Exposure Assessment describe the general concepts of exposure assessment including definitions and associated units, and by providing guidance on the planning and conducting of an exposure assessment. Guidance is also provided on presenting the results of the e...

  11. HUMAN EXPOSURE ACTIVITY PATTERNS

    EPA Science Inventory

    Human activity/uptake rate data are necessary to estimate potential human exposure and intake dose to environmental pollutants and to refine human exposure models. Personal exposure monitoring studies have demonstrated the critical role that activities play in explaining and pre...

  12. Regional disparities in the burden of disease attributable to unsafe water and poor sanitation in China

    PubMed Central

    Carlton, Elizabeth J; McDowell, Julia Z; Li, Huazhong; Luo, Wei; Remais, Justin V

    2012-01-01

    Abstract Objective To estimate the disease burden attributable to unsafe water and poor sanitation and hygiene in China, to identify high-burden groups and to inform improvement measures. Methods The disease burden attributable to unsafe water and poor sanitation and hygiene in China was estimated for diseases resulting from exposure to biologically contaminated soil and water (diarrhoeal disease, helminthiases and schistosomiasis) and vector transmission resulting from inadequate management of water resources (malaria, dengue and Japanese encephalitis). The data were obtained from China’s national infectious disease reporting system, national helminthiasis surveys and national water and sanitation surveys. The fraction of each health condition attributable to unsafe water and poor sanitation and hygiene in China was estimated from data in the Chinese and international literature. Findings In 2008, 327 million people in China lacked access to piped drinking water and 535 million lacked access to improved sanitation. The same year, unsafe water and poor sanitation and hygiene accounted for 2.81 million disability-adjusted life years (DALYs) and 62 800 deaths in the country, and 83% of the attributable burden was found in children less than 5 years old. Per capita DALYs increased along an east–west gradient, with the highest burden in inland provinces having the lowest income per capita. Conclusion Despite remarkable progress, China still needs to conduct infrastructural improvement projects targeting provinces that have experienced slower economic development. Improved monitoring, increased regulatory oversight and more government transparency are needed to better estimate the effects of microbiologically and chemically contaminated water and poor sanitation and hygiene on human health. PMID:22893741

  13. Cullin1 is up-regulated and associated with poor patients’ survival in hepatocellular carcinoma

    PubMed Central

    Liu, Wen; Wang, You; Zhang, Chuanling; Huang, Baoshan; Bai, Jin; Tian, Lijun

    2015-01-01

    Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cul1 in the development of hepatocellular carcinoma (HCC), we evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) containing 90 cases HCC tissues and paired adjacent non-cancerous tissues. We analyzed the correlation between Cul1 expression and clinicopathologic variables and patients survival using two independent HCC cohorts TMA. Our data showed that Cul1 expression was apparently increased in HCC tissues compared with paired adjacent non-tumor tissues. We also demonstrated that Cul1 staining was significantly correlated with tumor size, histology grade and TNM stage. Furthermore, we showed a strong correlation between high Cul1 expression and worse 5-year overall and disease-specific survival rates in HCC patients. Finally, univariate and multivariate Cox proportional hazards regression analysis investigated that high Cul1 expression was a strong independent prognostic indicator of HCC. Our data indicated that Cul1 may be an important prognosis marker for human HCC. PMID:26097587

  14. Changes in gene expression associated with radiation exposure

    SciTech Connect

    Woloschak, G.E.; Paunesku, T.; Chang-Liu, C.M.; Grdina, D.J.

    1995-12-31

    Current research from our group has demonstrated differences in gene induction patterns for high- and low-linear energy transfer radiations; some genes are induced selectively following neutron exposure, others selectively following {gamma}-ray exposure, and others induced following exposure to either. These genes are associated with a broad array of different functions including apoptosis, cytoskeletal function, and gene regulation (dd-RT-PCR) technology to identify genes induced following exposure to different qualities of radiation and following exposure to radiation in the presence of radioprotectors.

  15. Low Vagal Tone Magnifies the Association Between Psychosocial Stress Exposure and Internalizing Psychopathology in Adolescents

    PubMed Central

    McLaughlin, Katie A.; Rith-Najarian, Leslie; Dirks, Melanie A.; Sheridan, Margaret A.

    2014-01-01

    Vagal tone is a measure of cardiovascular function that facilitates adaptive responses to environmental challenge. Low vagal tone is associated with poor emotional and attentional regulation in children and has been conceptualized as a marker of sensitivity to stress. We investigated whether the associations of a wide range of psychosocial stressors with internalizing and externalizing psychopathology were magnified in adolescents with low vagal tone. Resting heart period data were collected from a diverse community sample of adolescents (ages 13–17; N =168). Adolescents completed measures assessing internalizing and externalizing psychopathology and exposure to stressors occurring in family, peer, and community contexts. Respiratory sinus arrhythmia (RSA) was calculated from the interbeat interval time series. We estimated interactions between RSA and stress exposure in predicting internalizing and externalizing symptoms and evaluated whether interactions differed by gender. Exposure to psychosocial stressors was associated strongly with psychopathology. RSA was unrelated to internalizing or externalizing problems. Significant interactions were observed between RSA and child abuse, community violence, peer victimization, and traumatic events in predicting internalizing but not externalizing symptoms. Stressors were positively associated with internalizing symptoms in adolescents with low RSA but not in those with high RSA. Similar patterns were observed for anxiety and depression. These interactions were more consistently observed for male than female individuals. Low vagal tone is associated with internalizing psychopathology in adolescents exposed to high levels of stressors. Measurement of vagal tone in clinical settings might provide useful information about sensitivity to stress in child and adolescent clients. PMID:24156380

  16. [The Impact of Sunlight Exposure on the Health of Older Adults].

    PubMed

    Lin, Tzu-Chia; Liao, Yen-Chi

    2016-08-01

    Appropriate exposure to sunlight not only contributes to the production of vitamin D, which has been associated with enhanced bone health, mood, and cognitive functions, but also regulates the secretion of melatonin, which has been associated with the mediation of circadian rhythms, improved sleep quality, and optimized physical and social activity in the elderly. However, damage to the skin, eyes, and immune system has also been widely associated with long-term exposure to sunlight. Several studies have shown that many elderly, especially those that reside in institutions, do not receive sufficient sunlight exposure. Institutionalized elderly tend to participate in indoor activities and spend significant periods of time alone and asleep in front of the television. Furthermore, factors such as poor health, environmental design, indoor/outdoor preference, and activity design may impact the access of institutionalized elderly to sunlight more than their non-institutionalized peers. Therefore, we suggest that in addition to obtaining sufficient levels of vitamin D from their diet and from supplements, the elderly should perform outdoor activities for 20-30 minutes a day for five days each week. Furthermore, we suggest that the environment of the care facility should be made be more accessible and that some activities should be held outdoors. PMID:27492302

  17. A Comparison of the Language Skills of ELLs and Monolinguals Who Are Poor Decoders, Poor Comprehenders, or Normal Readers

    ERIC Educational Resources Information Center

    Geva, Esther; Massey-Garrison, Angela

    2013-01-01

    The overall objective of this article is to examine how oral language abilities relate to reading profiles in English language learners (ELLs) and English as a first language (EL1) learners, and the extent of similarities and differences between ELLs and EL1s in three reading subgroups: normal readers, poor decoders, and poor comprehenders. The…

  18. Early Disparities in Mathematics Gains among Poor and Non-Poor Children: Examining the Role of Behavioral Engagement in Learning

    ERIC Educational Resources Information Center

    Robinson, Keith

    2013-01-01

    Multilevel modeling was used to investigate the relationship between poverty status, mathematics achievement gains, and behavioral engagement in learning over kindergarten. Data included information on 11,680 poor, low-income, and non-poor kindergartners from the Early Childhood Longitudinal Study-Kindergarten Cohort of 1998-1999 (ECLS-K). Results…

  19. Regulating the introduction of new chemicals under section 5 of TSCA: improving the efficiency of the process and reducing potential injury in the workplace through the use of operational MSDS and exposure limits.

    PubMed

    Rosenthal, I; Jayjock, M A; Keener, R L; Plamondon, J E

    1991-10-01

    The Toxic Substances Control Act (TSCA) authorizes the EPA to take appropriate actions to ensure that new and existing chemicals do not pose "unreasonable risk" to health or the environment. Section 2(b)(3) of the Act directs the Agency to accomplish this objective in a manner that does "not impede unduly or create unnecessary economic barriers to technological innovation." In recent years, critics have felt that the EPA has failed to achieve these primary goals of TSCA. This paper considers some of the reasons for this criticism and advocates an alternate approach of exposure limits and operationally sufficient controls to assist in achieving these goals. An illustration of how this alternate approach might work under practical conditions is presented, using as an example a new chemical substance from the class of acrylate monomers. These concepts and risk assessments provide data for a better design of future studies according to good laboratory practice and quality assurance. PMID:1669965

  20. The Cek1‑mediated MAP kinase pathway regulates exposure of α‑1,2 and β‑1,2‑mannosides in the cell wall of Candida albicans modulating immune recognition.

    PubMed

    Román, E; Correia, I; Salazin, A; Fradin, C; Jouault, T; Poulain, D; Liu, F-T; Pla, J

    2016-07-01

    The Cek1 MAP kinase (MAPK) mediates vegetative growth and cell wall biogenesis in the fungal pathogen Candida albicans. Alterations in the fungal cell wall caused by a defective Cek1‑mediated signaling pathway leads to increased β‑1,3‑glucan exposure influencing dectin‑1 fungal recognition by immune cells. We show here that cek1 cells also display an increased exposure of α‑1,2 and β‑1,2‑mannosides (α‑M and β‑M), a phenotype shared by strains defective in the activating MAPKK Hst7, suggesting a general defect in cell wall assembly. cek1 cells display walls with loosely bound material as revealed by transmission electron microscopy and are sensitive to tunicamycin, an inhibitor of N‑glycosylation. Transcriptomal analysis of tunicamycin treated cells revealed a differential pattern between cek1 and wild type cells which involved mainly cell wall and stress related genes. Mapping α‑M and β‑M epitopes in the mannoproteins of different cell wall fractions (CWMP) revealed an important shift in the molecular weight of the mannan derived from mutants defective in this MAPK pathway. We have also assessed the role of galectin‑3, a member of a β‑galactoside‑binding protein family shown to bind to and kill C. albicans through β‑M recognition, in the infection caused by cek1 mutants. Increased binding of cek1 to murine macrophages was shown to be partially blocked by lactose. Galectin-3(-/-) mice showed increased resistance to fungal infection, although galectin-3 did not account for the reduced virulence of cek1 mutants in a mouse model of systemic infection. All these data support a role for the Cek1‑mediated pathway in fungal cell wall maintenance, virulence and antifungal discovery. PMID:27191378

  1. Azathioprine during pregnancy in systemic lupus erythematosus patients is not associated with poor fetal outcome.

    PubMed

    Saavedra, Miguel Ángel; Sánchez, Antonio; Morales, Sara; Ángeles, Ulises; Jara, Luis Javier

    2015-07-01

    The objective of this study was to evaluate the risk of adverse fetal outcome in systemic lupus erythematosus (SLE) women exposed to azathioprine during pregnancy. We reviewed the medical records of SLE pregnant women followed from January 2005 to April 2013. The patients were evaluated at least once in each trimester and postpartum. Relevant fetal outcomes were extracted, such as rate of liveborns, fetal loss (spontaneous abortion and stillbirth), term delivery, preterm birth, neonatal death, low birth weight, low birth weight at term, and congenital malformations. A detailed history of drug use during pregnancy was obtained. We studied 178 pregnancies (in 172 women), 87 of them were exposed to azathioprine (AZA-group) and the remaining 91 were not exposed (NO AZA-group). Exposure to other drugs was similar in both groups. The rate of live births, spontaneous abortions mean birth weight, weeks of gestation, rate of birth weight <2500 g, and low birth weight at term did not differ between groups. No infant had major congenital abnormalities. Multivariate analysis showed that preeclampsia, premature rupture of membranes (PROM), lupus flare, and anti-DNA positive were associated with an increased risk of poor fetal outcome. Our study suggests that the use of azathioprine is safe and lacks of teratogenity in patients with SLE and pregnancy. Exposure to azathioprine during pregnancy is not associated with poor fetal outcome. PMID:26050103

  2. Sound exposure during outdoor music festivals.

    PubMed

    Tronstad, Tron V; Gelderblom, Femke B

    2016-01-01

    Most countries have guidelines to regulate sound exposure at concerts and music festivals. These guidelines limit the allowed sound pressure levels and the concert/festival's duration. In Norway, where there is such a guideline, it is up to the local authorities to impose the regulations. The need to prevent hearing-loss among festival participants is self-explanatory, but knowledge of the actual dose received by visitors is extremely scarce. This study looks at two Norwegian music festivals where only one was regulated by the Norwegian guideline for concert and music festivals. At each festival the sound exposure of four participants was monitored with noise dose meters. This study compared the exposures experienced at the two festivals, and tested them against the Norwegian guideline and the World Health Organization's recommendations. Sound levels during the concerts were higher at the festival not regulated by any guideline, and levels there exceeded both the national and the Worlds Health Organization's recommendations. The results also show that front-of-house measurements reliably predict participant exposure. PMID:27569410

  3. APPLYING EXPOSURE TOOLS TO SUPPORT HEALTH STUDIES

    EPA Science Inventory

    Air pollution from ambient sources continues to adversely impact human health in the United States. A fundamental goal for EPA is to implement air quality standards and regulations that reduce health risks associated with exposures to criteria pollutants and air toxics. However...

  4. ELEMENTAL SPECIATION IN ENVIRONMENTAL EXPOSURE ASSESSMENT MATRICES

    EPA Science Inventory

    Arsenic and tin are two trace metals where exposure assessments have moved towards a speciation based approach because the toxicity is very chemical form dependent. This toxicity difference can be one of many factors which influence the formulation of certain regulations. For a...

  5. Effects of Developmental Lead Exposure on the Hippocampal Transcriptome: Influences of Sex, Developmental Period, and Lead Exposure Level

    PubMed Central

    Schneider, Jay S

    2012-01-01

    Developmental lead (Pb) exposure has profound effects on cognition and behavior. Much is known about effects of Pb on hippocampal-mediated behaviors, but little is known about the molecular consequences of Pb exposure and the influences of developmental timing of exposure, level of exposure, and sex as effect modifiers of Pb exposure on the brain. The aim of this study was to examine the effects of different levels of Pb exposure (250 and 750 ppm Pb acetate) during perinatal (gestation/lactation) and postnatal (through postnatal day 45) periods on the hippocampal transcriptome in male and female Long Evans rats. Total RNA was extracted from hippocampus from four animals per experimental condition. RNA was hybridized to Affymetrix Rat Gene RNA Arrays using standard methods. Pb exposure per se influenced the expression of 717 transcripts (328 unique annotated genes), with many influenced in a sex-independent manner. Significant differences in gene expression patterns were also influenced by timing and level of exposure, with generally larger effects at the lower level of exposure across all groups. Statistically enriched biological functions included ion binding, regulation of RNA metabolic processes, and positive regulation of macromolecule biosynthetic processes. Processes of regulation of transcription and regulation of gene expression were preferentially enriched in males, regardless of timing or amount of Pb exposure. The effect on transcription factors and the diverse pathways or networks affected by Pb suggest a substantial effect of developmental Pb exposure on plasticity and adaptability, with these effects significantly modified by sex, developmental window of exposure, and level of Pb exposure. PMID:22641619

  6. A systems view of health care for the poor.

    PubMed Central

    Prasad, N.

    1989-01-01

    A systems view is a synthesis of health policy, medical sociology, public health, and common clinical problems to describe the current crisis in health care for the poor. Medical sociology and public health are particularly relevant to understand the complexity of clinical issues. Although preventive medicine is in desuetude, it is crucial if we are to reduce the future liability of postponed medical care among the poor. Medicaid metamorphosed to Medicare, as half of its outlays are spent on care of the elderly in nursing homes. Health care for the poor will remain a moral challenge to the architects of health policy and the medical profession. PMID:2659807

  7. HAT3-mediated acetylation of PCNA precedes PCNA monoubiquitination following exposure to UV radiation in Leishmania donovani

    PubMed Central

    Kumar, Devanand; Saha, Swati

    2015-01-01

    Histone modifications impact various processes. In examining histone acetyltranferase HAT3 of Leishmania donovani, we find elimination of HAT3 causes decreased cell viability due to defects in histone deposition, and aberrant cell cycle progression pattern. HAT3 associates with proliferating cell nuclear antigen (PCNA), helping load PCNA onto chromatin in proliferating cells. HAT3-nulls show heightened sensitivity to UV radiation. Following UV exposure, PCNA cycles off/on chromatin only in cells expressing HAT3. Inhibition of the ubiquitin-proteasome pathway prior to UV exposure allows accumulation of chromatin-bound PCNA, and reveals that HAT3-nulls are deficient in PCNA monoubiquitination as well as polyubiquitination. While poor monoubiquitination of PCNA may adversely affect translesion DNA synthesis-based repair processes, polyubiquitination deficiencies may result in continued retention of chromatin-bound PCNA, leading to genomic instability. On suppressing the proteasome pathway we also find that HAT3 mediates PCNA acetylation in response to UV. HAT3-mediated PCNA acetylation may serve as a flag for PCNA ubiquitination, thus aiding DNA repair. While PCNA acetylation has previously been linked to its degradation following UV exposure, this is the first report linking a HAT-mediated PCNA acetylation to PCNA monoubiquitination. These findings add a new dimension to our knowledge of the mechanisms regulating PCNA ubiquitination post-UV exposure in eukaryotes. PMID:25948582

  8. Silica gel as a particulate carrier of poorly water-soluble substances in aquatic toxicity testing.

    PubMed

    Breitholtz, Magnus; Ricklund, Niklas; Bengtsson, Bengt-Erik; Persson, N Johan

    2007-05-31

    Aquatic toxicity tests were originally developed for water-soluble substances. However, many substances are hydrophobic and thus poorly water-soluble, resulting in at least two major implications. Firstly, toxicity may not be reached within the range of water solubility of the tested compound(s), which may result in the formation of solids or droplets of the tested substance and consequently an uneven exposure. Secondly, because of multi-phase distribution of the tested substance it may be complicated to keep exposure concentrations constant. To overcome such problems, we have introduced silica gel as a particulate carrier in a toxicity test with the benthic copepod Nitocra spinipes. The main objective of the current study was to evaluate whether a controlled exposure could be achieved with the help of silica gel for testing single poorly water-soluble substances. A secondary objective was to evaluate whether an equilibrium mass balance model could predict internal concentrations that were consistent with the toxicity data and measured internal concentrations of two model hydrophobic substances, i.e., the polybrominated diphenyl ethers BDE-47 and BDE-99. Larval N. spinipes were exposed for 6 days to BDE-47 and BDE-99, respectively, in the silica gel test system and, for comparative reasons, in a similar and more traditional semi-static water test system. Via single initial amounts of the model substances administered on the silica gel, effects on both larval development and mortality resulted in higher and more concentration-related toxicity than in the water test system. We conclude that the silica gel test system enables a more controlled exposure of poorly water-soluble substances than the traditional water test system since the concentration-response relationship becomes distinct and there is no carrier solvent present during testing. Also, the single amount of added substance given in the silica gel test system limits the artefacts (e.g., increased chemical

  9. Population Density, Poor Sanitation, and Enteric Infections in Nueva Santa Rosa, Guatemala.

    PubMed

    Jarquin, Claudia; Arnold, Benjamin F; Muñoz, Fredy; Lopez, Beatriz; Cuéllar, Victoria M; Thornton, Andrew; Patel, Jaymin; Reyes, Lisette; Roy, Sharon L; Bryan, Joe P; McCracken, John P; Colford, John M

    2016-04-01

    Poor sanitation could pose greater risk for enteric pathogen transmission at higher human population densities because of greater potential for pathogens to infect new hosts through environmentally mediated and person-to-person transmission. We hypothesized that incidence and prevalence of diarrhea, enteric protozoans, and soil-transmitted helminth infections would be higher in high-population-density areas compared with low-population-density areas, and that poor sanitation would pose greater risk for these enteric infections at high density compared with low density. We tested our hypotheses using 6 years of clinic-based diarrhea surveillance (2007-2013) including 4,360 geolocated diarrhea cases tested for 13 pathogens and a 2010 cross-sectional survey that measured environmental exposures from 204 households (920 people) and tested 701 stool specimens for enteric parasites. We found that population density was not a key determinant of enteric infection nor a strong effect modifier of risk posed by poor household sanitation in this setting. PMID:26856919

  10. Population Density, Poor Sanitation, and Enteric Infections in Nueva Santa Rosa, Guatemala

    PubMed Central

    Jarquin, Claudia; Arnold, Benjamin F.; Muñoz, Fredy; Lopez, Beatriz; Cuéllar, Victoria M.; Thornton, Andrew; Patel, Jaymin; Reyes, Lisette; Roy, Sharon L.; Bryan, Joe P.; McCracken, John P.; Colford, John M.

    2016-01-01

    Poor sanitation could pose greater risk for enteric pathogen transmission at higher human population densities because of greater potential for pathogens to infect new hosts through environmentally mediated and person-to-person transmission. We hypothesized that incidence and prevalence of diarrhea, enteric protozoans, and soil-transmitted helminth infections would be higher in high-population-density areas compared with low-population-density areas, and that poor sanitation would pose greater risk for these enteric infections at high density compared with low density. We tested our hypotheses using 6 years of clinic-based diarrhea surveillance (2007–2013) including 4,360 geolocated diarrhea cases tested for 13 pathogens and a 2010 cross-sectional survey that measured environmental exposures from 204 households (920 people) and tested 701 stool specimens for enteric parasites. We found that population density was not a key determinant of enteric infection nor a strong effect modifier of risk posed by poor household sanitation in this setting. PMID:26856919

  11. 40 CFR 194.52 - Consideration of exposure pathways.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... COMPLIANCE WITH THE 40 CFR PART 191 DISPOSAL REGULATIONS Compliance Certification and Re-certification... compliance assessments that analyze compliance with § 191.15 of this chapter, all potential exposure...

  12. EXAMPLE EXPOSURE SCENARIOS ASSESSMENT TOOL

    EPA Science Inventory

    Exposure scenarios are a tool to help the assessor develop estimates of exposure, dose, and risk. An exposure scenario generally includes facts, data, assumptions, inferences, and sometimes professional judgment about how the exposure takes place. The human physiological and beh...

  13. The dark side of suibsidies: quantifying contaminant exposure to riparian predators via stream insects

    EPA Science Inventory

    Aquatic insects provide a critical nutrient subsidy to riparian food webs, yet their role as vectors of contaminants to terrestrial ecosystems is poorly understood. We investigated relationships between aquatic (resource utilization) and contaminant exposure for a riparian invert...

  14. VOLTAGE REGULATOR

    DOEpatents

    Von Eschen, R.L.; Scheele, P.F.

    1962-04-24

    A transistorized voltage regulator which provides very close voitage regulation up to about 180 deg F is described. A diode in the positive line provides a constant voltage drop from the input to a regulating transistor emitter. An amplifier is coupled to the positive line through a resistor and is connected between a difference circuit and the regulating transistor base which is negative due to the difference in voltage drop across thc diode and the resistor so that a change in the regulator output causes the amplifier to increase or decrease the base voltage and current and incrcase or decrease the transistor impedance to return the regulator output to normal. (AEC)

  15. [Poor, propertyless and pregnant: classification of women's status by country].

    PubMed

    1988-12-01

    A new study called "Poor, propertyless, and pregnant" that classified the condition of women in 99 countries found women in Sweden, Finland, and the US to enjoy the best legal and social conditions and the greatest degree of equality with men. The worst discrimination against women occurred in Bangladesh, Mali, Afghanistan, North Yemen, Pakistan, Nigeria, and Saudi Arabia. Women do not have complete equality with men in any country. But over 60% of the world's female population lives in countries where extensive poverty and sexual discrimination have created conditions of deprivation. One of the principal mechanisms that negatively influences the condition of women is early procreation; early and frequent childbirth obliterates women's chances for education and paid employment. Feminization of poverty is becoming universal, largely because a growing proportion of households are headed by women with dependent children. In developed and developing countries alike, working women with families work a double day. Although the struggle for legal and social equality for women takes different forms in different countries, certain basic measures can be applied by all governments. Reforms are needed to give women access to more remunerative jobs, equal property rights, and access to credit. Greater investments are needed in reproductive health and in education and training for women. Governments, employers, and husbands should recognize the social value of childbirth and child rearing. The study is divided into 5 sections, each of which has 4 series of data, so that each country is evaluated on 20 variables. The 5 sections are health, nuptiality and children, education, economic participation, and social equality. In most developed countries women live an average of 7 years longer than men, but in developing countries the difference is only 2 years. Complications of pregnancy and childbirth cause the deaths of over 500,000 women each year and affect another 5 million, mostly

  16. Restoring Blood Flow Beats Exercise for Poor Leg Circulation

    MedlinePlus

    ... news/fullstory_158683.html Restoring Blood Flow Beats Exercise for Poor Leg Circulation Opening vessels could prevent ... restore blood flow may have greater benefits than exercise, preliminary research suggests. People with peripheral artery disease ( ...

  17. Poor Weight Gain in Infants and Children (Beyond the Basics)

    MedlinePlus

    ... month) – Poor quality of suck (whether breast- or bottle-fed), incorrect formula preparation; breastfeeding problems; inadequate number ... to feed him/herself (eg, by holding a bottle or eating finger foods), but may need to ...

  18. Poor Sleep May Not Add to Cholesterol Problems, Study Finds

    MedlinePlus

    ... nih.gov/medlineplus/news/fullstory_157561.html Poor Sleep May Not Add to Cholesterol Problems, Study Finds ... disease risk factors such as high cholesterol, because sleep apnea -- another type of sleep disorder -- has been ...

  19. Los Angeles County Poor Farm, Patient Wards 201, 202, 203, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Los Angeles County Poor Farm, Patient Wards 201, 202, 203, 204, 205, 206, 207, 208 & 209 - Type A Plan, 7601 Imperial Highway; bounded by Esperanza Street, Hawthorn Avenue, Laurel Street, and Descanso Street, Downey, Los Angeles County, CA

  20. Los Angeles County Poor Farm, Patient Ward Nos. 210 & ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Los Angeles County Poor Farm, Patient Ward Nos. 210 & 211 - Type B Plan, 7601 Imperial Highway; bounded by Esperanza Street, Laurel Street, Flores Street, and Descanso Street, Downey, Los Angeles County, CA

  1. Poor Sleep May Worsen Thinking Problems in MS Patients

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159463.html Poor Sleep May Worsen Thinking Problems in MS Patients Study found link between severity of sleep apnea and performance on attention, memory tests To ...

  2. Poor Sleep May Worsen Thinking Problems in MS Patients

    MedlinePlus

    ... nih.gov/medlineplus/news/fullstory_159463.html Poor Sleep May Worsen Thinking Problems in MS Patients Study found link between severity of sleep apnea and performance on attention, memory tests To ...

  3. A Multiwavelength Investigation of Poor Clusters of Galaxies

    NASA Astrophysics Data System (ADS)

    Bliton, M.; Burns, J. O.; Voges, W.

    1999-12-01

    We present analysis of the X-ray, optical, and radio properties of a volume-limited sample of poor clusters of galaxies. Our poor cluster sample is composed of 339 groups in the redshift range 0.01-0.03, spanning the entire range of richness from very poor systems to Abell clusters. The multiwavelength properties of our sample were gathered from the ROSAT All-Sky Survey, the Palomar Digitized Sky Survey, and the Northern VLA Sky Survey. Properties discussed include X-ray luminosity, optical richness, spiral fraction, and radio fraction, among others. We also present a number of unique poor clusters that exhibit unexpected properties in the various wavelengths studied. This work was supported by NASA grant NAG5-6772 to M.B. & J.O.B.

  4. Many Hispanics, Poor Still Without Health Insurance: Report

    MedlinePlus

    ... fullstory_160507.html Many Hispanics, Poor Still Without Health Insurance: Report Majority live in states that haven't ... 2016 (HealthDay News) -- Despite an overall rise in health insurance coverage among all Americans, Hispanics, low-income earners ...

  5. Poor reading skills may involve a failure to focus attention.

    PubMed

    Silva-Pereyra, Juan; Bernal, Jorge; Rodríguez-Camacho, Mario; Yáñez, Guillermina; Prieto-Corona, Belén; Luviano, Lourdes; Hernández, Miguel; Marosi, Erzsebet; Guerrero, Vicente; Rodríguez, Héctor

    2010-01-01

    A source localization analysis was carried out to provide brain functional and structural assessments of individuals with poor reading skills. Standardized low-resolution brain electromagnetic tomography was used to locate sources of P2 and P3 event-related potential components in normal readers and in poor reader children performing a cued continuous performance task. Cue-elicited P2 sources in the right superior parietal gyrus were smaller in 37 poor readers than in 40 normal readers. Poor readers showed a higher P3 activation in response to a false target in frontal and frontorbital regions than normal readers. These results suggest that reading disabilities may be attributed to failures in attentional focalization for incoming stimuli. PMID:19996811

  6. Depleting depletion: Polymer swelling in poor solvent mixtures

    NASA Astrophysics Data System (ADS)

    Mukherji, Debashish; Marques, Carlos; Stuehn, Torsten; Kremer, Kurt

    A polymer collapses in a solvent when the solvent particles dislike monomers more than the repulsion between monomers. This leads to an effective attraction between monomers, also referred to as depletion induced attraction. This attraction is the key factor behind standard polymer collapse in poor solvents. Strikingly, even if a polymer exhibits poor solvent condition in two different solvents, it can also swell in mixtures of these two poor solvents. This collapse-swelling-collapse scenario is displayed by poly(methyl methacrylate) (PMMA) in aqueous alcohol. Using molecular dynamics simulations of a thermodynamically consistent generic model and theoretical arguments, we unveil the microscopic origin of this phenomenon. Our analysis suggests that a subtle interplay of the bulk solution properties and the local depletion forces reduces depletion effects, thus dictating polymer swelling in poor solvent mixtures.

  7. Intermittent heat exposure and thirst in rats.

    PubMed

    Barney, Christopher C; Kuhrt, David M

    2016-04-01

    Adequate water intake, supporting both cardiovascular function and evaporative cooling, is a critical factor in mitigating the effects of heat waves, which are expected to increase with global warming. However, the regulation of water intake during periods of intermittent heat exposure is not well understood. In this study, the effects of access to water or no access during intermittent heat exposure were assessed using male Sprague-Dawley rats exposed to 37.5°C for 4 h/day. After 7 days of intermittent heat exposure, reductions in evaporative water loss were observed in all animals and reductions in water intake following heat exposure occurred as the days of heat exposure increased. Rats that were not allowed water during the 7 days of exposure had decreased rehydration levels, however, rats allowed access to water increased water intake during exposure and exhibited higher overall rehydration levels over the same time period. Peripheral administration of angiotensinII, mimicking activation of volemic thirst, or hypertonic saline solution, activating intracellular thirst, did not result in alteration of water intake in rats exposed to heat with access to water compared to control rats. In contrast, rats exposed to heat without access to water had reduced water intake after administration of hypertonic saline and increased water intake after administration of angiotensinIIcompared to control rats. These experiments demonstrate that thirst responses to intermittent heat exposure are altered by providing water during heat exposure and that intermittent heat exposure without access to water alters drinking responses to both intracellular and extracellular thirst challenges. PMID:27095836

  8. Explaining the Role of Proximate Determinants on Fertility Decline among Poor and Non-Poor in Asian Countries

    PubMed Central

    Majumder, Nabanita; Ram, Faujdar

    2015-01-01

    Objectives We examined the overall contributions of the poor and non-poor in fertility decline across the Asian countries. Further, we analyzed the direct and indirect factors that determine the reproductive behaviour of two distinct population sub-groups. Design Data from several new rounds of DHS surveys are available over the past few years. The DHS provides cross-nationally comparable and useful data on fertility, family planning, maternal and child health along with the other information. Six selected Asian countries namely: Bangladesh, India, Indonesia, Nepal, Philippines, and Vietnam are considered for the purpose of the study. Three rounds of DHS surveys for each country (except Vietnam) are considered in the present study. Methods Economic status is measured by computing a “wealth index”, i.e. a composite indicator constructed by aggregating data on asset ownership and housing characteristics using principal components analysis (PCA). Computed household wealth index has been broken into three equal parts (33.3 percent each) and the lowest and the highest 33.3 percent is considered as poor and non-poor respectively. The Bongaarts model was employed to quantify the contribution of each of the proximate determinants of fertility among poor and non-poor women. Results Fertility reduction across all population subgroups is now an established fact despite the diversity in the level of socio-economic development in Asian countries. It is clear from the analysis that fertility has declined irrespective of economic status at varying degrees within and across the countries which can be attributed to the increasing level of contraceptive use especially among poor women. Over the period of time changing marriage pattern and induced abortion are playing an important role in reducing fertility among poor women. Conclusions Fertility decline among majority of the poor women across the Asian countries is accompanied by high prevalence of contraceptive use followed by

  9. Does overgeneral autobiographical memory result from poor memory for task instructions?

    PubMed

    Yanes, Paula K; Roberts, John E; Carlos, Erica L

    2008-10-01

    Considerable previous research has shown that retrieval of overgeneral autobiographical memories (OGM) is elevated among individuals suffering from various emotional disorders and those with a history of trauma. Although previous theories suggest that OGM serves the function of regulating acute negative affect, it is also possible that OGM results from difficulties in keeping the instruction set for the Autobiographical Memory Test (AMT) in working memory, or what has been coined "secondary goal neglect" (Dalgleish, 2004). The present study tested whether OGM is associated with poor memory for the task's instruction set, and whether an instruction set reminder would improve memory specificity over repeated trials. Multilevel modelling data-analytic techniques demonstrated a significant relationship between poor recall of instruction set and probability of retrieving OGMs. Providing an instruction set reminder for the AMT relative to a control task's instruction set improved memory specificity immediately afterward. PMID:18608978

  10. Physical properties of luminous dust-poor quasars

    SciTech Connect

    Jun, Hyunsung David; Im, Myungshin E-mail: mim@astro.snu.ac.kr

    2013-12-20

    We identify and characterize a population of luminous, dust-poor quasars at 0 < z < 5 that is photometrically similar to objects previously found at z > 6. This class of active galactic nuclei is known to show little IR emission from dusty structure, but it is poorly understood in terms of number evolution and dependence on physical quantities. To better understand the properties of these quasars, we compile a rest-frame UV to IR library of 41,000 optically selected type 1 quasars with L {sub bol} > 10{sup 45.7} erg s{sup –1}. After fitting the broadband spectral energy distributions (SEDs) with accretion disk and dust components, we find 0.6% of our sample to be hot dust-poor, with rest-frame 2.3 μm to 0.51 μm flux density ratios of –0.5 dex or less. The dust-poor SEDs are blue in the UV-optical and weak in the mid-IR, such that their accretion disks are less obscured and the hot dust emission traces that of warm dust down to the dust-poor regime. At a given bolometric luminosity, dust-poor quasars are lower in black hole mass and higher in Eddington ratio than general luminous quasars, suggesting that they are in a rapidly growing evolutionary state in which the dust-poor phase appears as a short or rare phenomenon. The dust-poor fraction increases with redshift, and possible implications for their evolution are discussed.

  11. Inference in {open_quotes}poor{close_quotes} languages

    SciTech Connect

    Petrov, S.

    1996-12-31

    Languages with a solvable implication problem but without complete and consistent systems of inference rules ({open_quote}poor{close_quote} languages) are considered. The problem of existence of a finite, complete, and consistent inference rule system for a {open_quotes}poor{close_quotes} language is stated independently of the language or the rule syntax. Several properties of the problem are proved. An application of the results to the language of join dependencies is given.

  12. Kinematics and dynamics of the Morgan poor clusters

    NASA Astrophysics Data System (ADS)

    Bird, Christina M.; Beers, Timothy C.; Kriessler, Jeffrey R.; Huchra, John P.

    1995-07-01

    Eighteen of the 23 MKW and AWM poor clusters now have 10 or more measured redshifts within 1.5h-1 Mpc of the central galaxy; 11 clusters have at least 20 measured redshifts. Based on the 21 clusters for which we have sufficient velocity information, the median velocity scale is 336 km s-1, a factor of two smaller than found for rich clusters. Several of the poor clusters exhibit complex velocity distributions due to the presence of nearby clumps of galaxies. We check on the velocity of the dominant galaxy in each poor cluster relative to the remaining cluster members. Significantly high relative velocities of the dominant galaxy are found in only 4 of 21 poor clusters, 3 of which we suspect are due to contamination of the parent velocity distribution. Several statistical tests indicate that the D/cD galaxies are at the kinematic centers of the parent poor cluster velocity distributions. Mass-to-light ratios for the 13 of the 15 poor clusters for which we have the required data are in the range 50<=M/LB(0)<=200 Msolar/Lsolar.

  13. Clinicopathological significance of gastric poorly differentiated medullary carcinoma.

    PubMed

    Hirai, Hideaki; Yoshizawa, Tadashi; Morohashi, Satoko; Haga, Toshihiro; Wu, Yunyan; Ota, Rie; Takatsuna, Masafumi; Akasaka, Harue; Hakamada, Kenichi; Kijima, Hiroshi

    2016-01-01

    Poorly differentiated gastric adenocarcinoma of solid type is known to show a clinicopathological diversity, but its morphological characteristics have rarely been investigated. In this study, we defined poorly differentiated medullary carcinoma indicating the following three characteristics: (i) more than 90% of the entire tumor were composed of poorly differentiated adenocarcinoma in a medullary growth, (ii) the tumor exhibited an expansive growth at the tumor margin, and (iii) special types such as an α-fetoprotein-producing carcinoma, neuroendocrine carcinoma, and carcinoma with lymphoid stroma were excluded. Based on the definition, we subclassified the poorly differentiated gastric adenocarcinoma of solid type into the two groups: medullary carcinoma and non-medullary carcinoma, and clinicopathologically analyzed 23 cases of medullary carcinomas and 38 cases of non-medullary carcinomas. The medullary carcinomas less frequently displayed lymphatic invasion, venous invasion, and lymph node metastasis, compared with the non-medullary carcinoma (P < 0.001, P = 0.002, and P < 0.001, respectively). The patients with medullary carcinomas significantly showed better disease-free survival (P = 0.017). This is the first study to demonstrate that poorly differentiated adenocarcinoma of solid type can be subclassified into tumors with low and high malignant potentials. Gastric poorly differentiated medullary carcinoma is considered to be a novel histological type predicting good patients' prognosis. PMID:27108877

  14. Skin Exposure and Asthma

    PubMed Central

    Redlich, Carrie A.

    2010-01-01

    Numerous occupational and environmental exposures that increase asthma risk have been identified. Research and prevention have focused primarily on the respiratory tract. However, recent studies suggest that the skin may also be an important route of exposure and site of sensitization that contributes to asthma development. Factors that impair skin barrier function, such as filaggrin gene mutations or skin trauma, may facilitate allergen entry and promote Th2-like sensitization and subsequent asthma. Animal studies demonstrate that skin exposure to chemical and protein allergens is highly effective at inducing sensitization, with subsequent inhalation challenge eliciting asthmatic responses. A similar role for human skin exposure to certain sensitizing agents, such as isocyanates, is likely. Skin exposure methodologies are being developed to incorporate skin exposure assessment into epidemiology studies investigating asthma risk factors. PMID:20427586

  15. Estimated exposure to EU regulated mycotoxins and risk characterization of aflatoxin-induced hepatic toxicity through the consumption of the toasted cereal flour called "gofio", a traditional food of the Canary Islands (Spain).

    PubMed

    Luzardo, Octavio P; Bernal-Suárez, María Del Mar; Camacho, María; Henríquez-Hernández, Luis Alberto; Boada, Luis D; Rial-Berriel, Cristian; Almeida-González, Maira; Zumbado, Manuel; Díaz-Díaz, Ricardo

    2016-07-01

    "Gofio" is a type of flour made from toasted grain, which is part of the staple food in the Canary Islands, Spain, in which the occurrence of Aflatoxins B1, B2, G1 and G2 (AFB1, AFB2, AFG1, AFG2), Fumonisins B1 and B2 (FB1 and FB2) Ochratoxin A (OTA), Deoxynivalenol (DNV) and Zearalenone (ZEA) was evaluated. 83% of the samples were contaminated with at least one mycotoxin and 69.2% of the analyzed samples showed co-occurrence of mycotoxins (range 2 to 8). All the concentrations were well below the established limits (maximum values of AFs=0.42 μg/kg; FBs=178.3 μg/kg; OTA=0.3 μg/kg; DON=92.5 μg/kg; and ZEA=9.9 μg/kg). The daily dietary exposure to total AFs was estimated to be 7.1% of the TDI. This value was almost double in children, and considering the upper-bound approach could reach 35% of the TDI. For the rest of mycotoxins, the consumers would be exposed to less than 2% of their TDIs. The risk characterization indicates that there is a potential risk in developing aflatoxin induced liver cancer due to gofio consumption in the subpopulation which is simultaneously exposed to other hepatocarcinogens, such as the hepatitis B virus. PMID:27132021

  16. URI1 amplification in uterine carcinosarcoma associates with chemo-resistance and poor prognosis

    PubMed Central

    Wang, Yu; Garabedian, Michael J; Logan, Susan K

    2015-01-01

    Uterine carcinosarcoma (UCS) is a rare type of cancer and accounts for 5% of uterine malignancies. However, UCS patients suffer a high prevalence of chemo-resistance and a very poor prognosis compared to uterine cancer patients. URI is a chaperone with functions in transcription. We analyzed the somatic URI1 copy number variation in 57 post-menopausal non-metastatic UCS patients in comparison to 363 uterine corpus endometrial carcinomas. URI1 amplification was detected in 40% (23/57) of primary UCS and 5.5% (20/363) of uterine carcinomas. UCS patients with URI1 amplification exhibited 13% (3/23) tumor-free survival compared to 41% (14/34) in the absence of URI amplification (P=0.023). URI1 amplification (OR=6.54, P=0.027), weight (OR=1.068, P=0.024), hypertension (OR=3.35, P=0.044), and tumor stage (OR=2.358, P=0.018) associated with poor survival. Patients treated with hormone replacement therapy (OR=15.87, P=0.011) displayed enhanced overall survival. Combined radiation and chemotherapy improved patient survival (median survival=2043 days) compared to single (median survival=597 days) or no treatment (median survival=317 days, P=0.0016). Importantly, patients with URI1 amplification had poor response to adjuvant treatment compared to control group (P=0.013). Tumors with URI1 amplification displayed decreased transcription of genes encoding tumor suppressor and apoptotic regulators and increased expression of genes regulating oncogenesis, survival and metastasis. Overexpression of URI1 in a cultured cell model induced ATM expression and resistance to cisplatin. Our findings suggest that high prevalence in UCS may associate with poor prognosis and worse response to adjuvant treatment. PMID:26328264

  17. Excessive Biologic Response to IFNβ Is Associated with Poor Treatment Response in Patients with Multiple Sclerosis

    PubMed Central

    Rani, M. R. Sandhya; Xu, Yaomin; Lee, Jar-Chi; Na, Jie; Shrock, Jennifer; Josyula, Anupama; Fisher, Elizabeth

    2011-01-01

    Background Interferon-beta (IFNβ) is used to inhibit disease activity in multiple sclerosis (MS), but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified. Methods The relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70) or poor response (n = 15). Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs). Results The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual ‘IFN response fingerprint’. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections. Conclusion MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients. PMID:21602934

  18. Maternal and early life arsenite exposure impairs neurodevelopment and increases the expression of PSA-NCAM in hippocampus of rat offspring.

    PubMed

    Luo, Jiaohua; Qiu, Zhiqun; Chen, Ji'an; Zhang, Liang; Liu, Wenyi; Tan, Yao; Shu, Weiqun

    2013-09-15

    Although epidemiological investigations indicate that chronic arsenic exposure can induce developmental neurotoxicity in children, the molecular mechanisms are still poorly understood. Neural cell adhesion molecules (NCAMs) play critical roles during the development of nervous system. Polysialylation of NCAM (PSA-NCAM) is a critical functional feature of NCAM-mediated cell interactions and functions. The present study aimed at investigating the effects of maternal and early life arsenite exposure on NCAM and PSA-NCAM in rat offspring. To this end, mother rats were divided into three groups and exposed to 0, 2.72 and 13.6mg/L sodium arsenite, respectively, during gestation and lactation. After weaning, rat offspring drank the same solution as their mothers. Neural reflex parameters, arsenic level of hippocampus, ultra-structural changes of hippocampus, the expression of NCAM, PSA-NCAM and two polysialyltransferases (STX and PST) in rat offspring were assessed. Arsenite exposure significantly prolonged the time of completing reflex response of surface righting, negative geotaxis and cliff avoidance of rat offspring in 13.6mg/L As-exposed group. Neurons and capillaries presented pathological changes and the expression of NCAM, PSA-NCAM, STX and PST were up-regulated in hippocampus of rat offspring exposed to arsenite. These results indicated that maternal arsenite exposure increases the expression of PSA-NCAM, NCAM and polysialyltransferases in hippocampus of rat offspring on postnatal day (PND) 21 and PND120, which might contribute to the impaired neurodevelopment following arsenite exposure. PMID:23811142

  19. Biomarkers of xenobiotic exposures

    SciTech Connect

    Brewster, M.A.

    1988-07-01

    Direct measurement of xenobiotic (foreign) chemicals is not always feasible as an exposure assessment,--owing to rapid metabolism, sequestration into fatty tissues, or lack of suitable assay methods. Furthermore, suspect exposures often involve complex mixtures of organics. In these circumstances, indirect biomarkers of exposure can be most helpful. This paper reviews four urinary parameters that hold promise as biomarkers of exposure in occupational and environmental settings: glucaric acid (end-product of the glucuronidation pathway), thioethers (end-product of glutathione reaction with electrophilic or alkylating agents), porphyrin pattern (altered with disruption in heme biosynthesis), and the Ames mutagenicity test. 112 references.

  20. Extracting phonological patterns for L2 word learning: the effect of poor phonological awareness.

    PubMed

    Hu, Chieh-Fang

    2014-10-01

    An implicit word learning paradigm was designed to test the hypothesis that children who came to the task of L2 vocabulary acquisition with poorer L1 phonological awareness (PA) are less capable of extracting phonological patterns from L2 and thus have difficulties capitalizing on this knowledge to support L2 vocabulary learning. A group of Chinese-speaking six-grade students took a multi-trial L2 (English) word learning task after being exposed to a set of familiar words that rhymed with the target words. Children's PA was measured at grade 3. Children with relatively poorer L1 PA and those with better L1 PA did not differ in identifying the forms of the new words. However, children with poorer L1 PA demonstrated reduced performance in naming pictures with labels that rhymed with the pre-exposure words than with labels that did not rhyme with the pre-exposure words. Children with better L1 PA were not affected by the recurring rime shared by the pre-exposure words and the target words. These findings suggest that poor L1 PA may impede L2 word learning via difficulty in abstracting phonological patterns away from L2 input to scaffold word learning. PMID:24043509

  1. [The autonomic regulation of the cardiovascular system in subjects with the autonomic dystonia syndrome subjected to ionizing radiation exposure as a result of the accident at the Chernobyl Atomic Electric Power Station].

    PubMed

    Niagu, A I; Zazimko, R N

    1995-01-01

    180 males in the age of 21-50, all the participants of Chernobyl accident consequences liquidation were examined. In all individuals vegetative dystonia (VD) syndrome was diagnosed (total radiation doses 0.1-1.0 Grey according to D. Erwin method). It was established that VD syndrome differed in these persons by pronounced stages of disorders manifestation as well as by polymorphism of vegetative disturbances. These findings testify central and peripheral vegetative nervous system parts involvement. In 40.2% of cases in individuals which were examined in rest and in 56.2% after dosed physical loading the functional disorders of vegetative cardiovascular system regulation of vagal type mainly (76.5%) were revealed. Clear correlation was not observed between vegetative disorders and radiation dose value. The estimation of contribution of each of the possible pathogenic factors (exactly stressogenic, radioactive and others) in vegetative disturbances development is not possible now. PMID:8533503

  2. Health System Challenges in Organizing Quality Diabetes Care for Urban Poor in South India

    PubMed Central

    Bhojani, Upendra; Devedasan, Narayanan; Mishra, Arima; De Henauw, Stefaan; Kolsteren, Patrick; Criel, Bart

    2014-01-01

    Background Weak health systems in low- and middle-income countries are recognized as the major constraint in responding to the rising burden of chronic conditions. Despite recognition by global actors for the need for research on health systems, little attention has been given to the role played by local health systems. We aim to analyze a mixed local health system to identify the main challenges in delivering quality care for diabetes mellitus type 2. Methods We used the health system dynamics framework to analyze a health system in KG Halli, a poor urban neighborhood in South India. We conducted semi-structured interviews with healthcare providers located in and around the neighborhood who provide care to diabetes patients: three specialist and 13 non-specialist doctors, two pharmacists, and one laboratory technician. Observations at the health facilities were recorded in a field diary. Data were analyzed through thematic analysis. Result There is a lack of functional referral systems and a considerable overlap in provision of outpatient care for diabetes across the different levels of healthcare services in KG Halli. Inadequate use of patients’ medical records and lack of standard treatment protocols affect clinical decision-making. The poor regulation of the private sector, poor systemic coordination across healthcare providers and healthcare delivery platforms, widespread practice of bribery and absence of formal grievance redress platforms affect effective leadership and governance. There appears to be a trust deficit among patients and healthcare providers. The private sector, with a majority of healthcare providers lacking adequate training, operates to maximize profit, and healthcare for the poor is at best seen as charity. Conclusions Systemic impediments in local health systems hinder the delivery of quality diabetes care to the urban poor. There is an urgent need to address these weaknesses in order to improve care for diabetes and other chronic

  3. Latitudinal exposure to DDTs, HCB, PCBs, PBDEs and DP in giant petrels (Macronectes spp.) across the Southern Ocean.

    PubMed

    Roscales, Jose L; González-Solís, Jacob; Zango, Laura; Ryan, Peter G; Jiménez, Begoña

    2016-07-01

    Studies on Persistent Organic Pollutants (POPs) in Antarctic wildlife are scarce, and usually limited to a single locality. As a result, wildlife exposure to POPs across the Southern Ocean is poorly understood. In this study, we report the differential exposure of the major southern ocean scavengers, the giant petrels, to POPs across a wide latitudinal gradient. Selected POPs (PCBs, HCB, DDTs, PBDEs) and related compounds, such as Dechlorane Plus (DP), were analyzed in plasma of southern giant petrels (Macronectes giganteus) breeding on Livingston (62°S 61°W, Antarctica), Marion (46°S 37°E, sub-Antarctic), and Gough (40°S 10°W, cool temperate) islands. Northern giant petrels (Macronectes halli) from Marion Island were also studied. Stable isotope ratios of C and N (δ(13)C and δ(15)N) were used as dietary tracers of the marine habitat and trophic level, respectively. Breeding locality was a major factor explaining petrel exposure to POPs compared with species and sex. Significant relationships between δ(13)C values and POP burdens, at both inter- and intra-population levels, support latitudinal variations in feeding grounds as a key factor in explaining petrel pollutant burdens. Overall, pollutant levels in giant petrels decreased significantly with latitude, but the relative abundance (%) of the more volatile POPs increased towards Antarctica. DP was found at negligible levels compared with legacy POPs in Antarctic seabirds. Spatial POP patterns found in giant petrels match those predicted by global distribution models, and reinforce the hypothesis of atmospheric long-range transport as the main source of POPs in Antarctica. Our results confirm that wildlife movements out of the polar region markedly increase their exposure to POPs. Therefore, strategies for Antarctic wildlife conservation should consider spatial heterogeneity in exposure to marine pollution. Of particular relevance is the need to clarify the exposure of Antarctic predators to emerging

  4. Extracellular Vesicles from Caveolin-Enriched Microdomains Regulate Hyaluronan-Mediated Sustained Vascular Integrity

    PubMed Central

    Mirzapoiazova, Tamara; Lennon, Frances E.; Mambetsariev, Bolot; Allen, Michael; Riehm, Jacob; Poroyko, Valeriy A.; Singleton, Patrick A.

    2015-01-01

    Defects in vascular integrity are an initiating factor in several disease processes. We have previously reported that high molecular weight hyaluronan (HMW-HA), a major glycosaminoglycan in the body, promotes rapid signal transduction in human pulmonary microvascular endothelial cells (HPMVEC) leading to barrier enhancement. In contrast, low molecular weight hyaluronan (LMW-HA), produced in disease states by hyaluronidases and reactive oxygen species (ROS), induces HPMVEC barrier disruption. However, the mechanism(s) of sustained barrier regulation by HA are poorly defined. Our results indicate that long-term (6–24 hours) exposure of HMW-HA induced release of a novel type of extracellular vesicle from HLMVEC called enlargeosomes (characterized by AHNAK expression) while LMW-HA long-term exposure promoted release of exosomes (characterized by CD9, CD63, and CD81 expression). These effects were blocked by inhibiting caveolin-enriched microdomain (CEM) formation. Further, inhibiting enlargeosome release by annexin II siRNA attenuated the sustained barrier enhancing effects of HMW-HA. Finally, exposure of isolated enlargeosomes to HPMVEC monolayers generated barrier enhancement while exosomes led to barrier disruption. Taken together, these results suggest that differential release of extracellular vesicles from CEM modulate the sustained HPMVEC barrier regulation by HMW-HA and LMW-HA. HMW-HA-induced specialized enlargeosomes can be a potential therapeutic strategy for diseases involving impaired vascular integrity. PMID:26447809

  5. Education of Poor Children as an Answer to a Social and Economic Crisis: Dutch Local Government Policies in the Eighteenth Century

    ERIC Educational Resources Information Center

    van Gijlswijk, T. W. M.

    2011-01-01

    Local administrations in the Republic of the United Netherlands determined in the seventeenth and eighteenth century the conditions of the local educational provisions. Several towns published separate regulations for educating poor children in separate schools. Others left the responsibility to local charity committees. The regulations are…

  6. Characterization of fibronectin type III domain-containing protein 5 (FNDC5) gene in chickens: Cloning, tissue expression, and regulation of its expression in the muscle by fasting and cold exposure.

    PubMed

    Li, Xin; Fang, Wenqian; Hu, Yuanyuan; Wang, Yajun; Li, Juan

    2015-10-10

    Irisin, a novel myokine encoded by fibronectin type III domain-containing protein 5 gene (FNDC5), is reported to stimulate brown fat-like development of white fat tissue and thermogenesis in mammals recently. However, information about the structure, tissue expression, and roles of FNDC5/irisin remains unknown in non-mammalian vertebrates including birds. In this study, we first cloned the FNDC5 (cFNDC5) cDNA from chickens. cFNDC5 is predicted to encode a 220-amino acid precursor containing the putative 'irisin peptide' of 112 amino acids, which shows high amino acid sequence identity with irisin of humans (97%), mice (97%), anole lizards (93%) and zebrafish (~80%). Using quantitative real-time PCR, we further examined cFNDC5 mRNA expression in chicken tissues. The results showed that in adult chickens, cFNDC5 is abundantly expressed in the muscle, heart, pituitary, ovary and various brain regions, and moderately expressed in adipose tissue, kidneys, lung, testes and small intestine. Moreover, cFNDC5 is also abundantly expressed in the muscle, brain, hypothalamus and pituitary of developing embryos and post-hatching chicks. Interestingly, we noted that cFNDC5 expression in the muscle of 3-week-old chicks could be induced by fasting and cold exposure, while its expression decreases during differentiation of pre-adipocytes cultured in vitro. Collectively, our data suggest that FNDC5/irisin is more than a 'myokine' and may be related to the development/functions of many tissues (e.g. muscle, brain, fat), as well as metabolic status of chickens. PMID:26072164

  7. Homelessness, Violence Exposure, and School Participation among Urban Adolescent Mothers

    ERIC Educational Resources Information Center

    Kennedy, Angie C.

    2007-01-01

    Using a risk and resilience framework, this exploratory study examines the relationships between homelessness, exposure to multiple types of violence, and school participation within a survey sample of poor adolescent mothers living in an urban setting. Participants who were homeless either currently or historically were compared with participants…

  8. Summer Study: A Two Part Investigation of the Impact of Exposure to Schooling on Achievement Growth.

    ERIC Educational Resources Information Center

    David, Jane Lisa

    This thesis is composed of two studies which look at the impact of exposure to schooling on achievement growth of children. Both use data from the National Follow Through Evaluation. The first study investigates the hypothesis that the difference in achievement growth between poor and non-poor children is greater during the summer months than…

  9. Prenatal immunotoxicant exposure and postnatal autoimmune disease.

    PubMed Central

    Holladay, S D

    1999-01-01

    Reports in humans and rodents indicate that immune development may be altered following perinatal exposure to immunotoxic compounds, including chemotherapeutics, corticosteroids, polycyclic hydrocarbons, and polyhalogenated hydrocarbons. Effects from such exposure may be more dramatic or persistent than following exposure during adult life. For example, prenatal exposure to the insecticide chlordane or to the polycyclic aromatic hydrocarbon benzo[(italic)a(/italic)]pyrene produces what appears to be lifelong immunosuppression in mice. Whether prenatal immunotoxicant exposure may predispose the organism to postnatal autoimmune disease remains largely unknown. In this regard, the therapeutic immunosuppressant cyclosporin A (CsA) crosses the placenta poorly. However, lethally irradiated rodents exposed to CsA postsyngeneic bone marrow transplant (i.e., during re-establishment of the immune system) develop T-cell-mediated autoimmune disease, suggesting this drug may produce a fundamental disruption in development of self-tolerance by T cells. The environmental contaminant 2,3,7, 8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD) crosses the placenta and produces fetal thymic effects (italic)in vivo(/italic) similar to effects of CsA in fetal thymic organ culture, including inhibited thymocyte maturation and reduced expression of thymic major histocompatability complex class II molecules. These observations led to the suggestion that gestational exposure to TCDD may interfere with normal development of self-tolerance. Possibly supporting this hypothesis, when mice predisposed to development of autoimmune disease were treated with TCDD during gestation, postnatal autoimmunity was exacerbated. Similar results have been reported for mice exposed to diethylstilbestrol during development. These reports suggest that prenatal exposure to certain immunotoxicants may play a role in postnatal expression of autoimmunity. PMID:10502532

  10. Unregulated usage of labour-inducing medication in a region of Pakistan with poor drug regulatory control: characteristics and risk patterns

    PubMed Central

    Shah, Safieh; Van den Bergh, Rafael; Prinsloo, Jeanne Rene; Rehman, Gulalai; Bibi, Amna; Shaeen, Neelam; Auat, Rosa; Daudi, Sabina Mutindi; Njenga, Joyce Wanjiru; Khilji, Tahir Bashir-ud-Din; Maïkéré, Jacob; De Plecker, Eva; Caluwaerts, Séverine; Zachariah, Rony; Van Overloop, Catherine

    2016-01-01

    Background In developing countries such as Pakistan, poor training of mid-level cadres of health providers, combined with unregulated availability of labour-inducing medication can carry considerable risk for mother and child during labour. Here, we describe the exposure to labour-inducing medication and its possible risks in a vulnerable population in a conflict-affected region of Pakistan. Methods A retrospective cohort study using programme data, compared the outcomes of obstetric risk groups of women treated with unregulated oxytocin, with those of women with regulated treatment. Results Of the 6379 women included in the study, 607 (9.5%) received labour-inducing medication prior to reaching the hospital; of these, 528 (87.0%) received unregulated medication. Out of 528 labour-inducing medication administrators, 197 (37.3%) traditional birth attendants (also known as dai) and 157 (29.7%) lady health workers provided unregulated treatment most frequently. Women given unregulated medication who were diagnosed with obstructed/prolonged labour were at risk for uterine rupture (RR 4.1, 95% CI: 1.7–9.9) and severe birth asphyxia (RR 3.9, 95% CI: 2.5–6.1), and those with antepartum haemorrhage were at risk for stillbirth (RR 1.8, 95% CI: 1.0–3.1). Conclusions In a conflict-affected region of Pakistan, exposure to unregulated treatment with labour-inducing medication is common, and carries great risk for mother and child. Tighter regulatory control of labour-inducing drugs is needed, and enhanced training of the mid-level cadres of healthcare workers is required. PMID:26276813

  11. Very Metal-poor Stars in the RAVE Spectroscopic Survey

    NASA Astrophysics Data System (ADS)

    Matijevic, Gal

    2015-08-01

    Metal-poor stars have been the cornerstone of the galactic and stellar archeology for decades. Due to their intact nature they offer a unique insight into the early stages of the galactic evolution and help us understand the nucleosynthesis processes responsible for the creation of chemical elements. The number of discovered very metal-poor stars (metallicity [Fe/H] < -2.0) is still relatively low and it drops sharply towards even lower metallicities. Only a handful of known stars have [Fe/H] < -4.0. RAVE spectroscopic survey enabled us to serendipitously discover many new metal-poor stars due to its large sample size and the fact that its wavelength range is centered around the infra-red CaII triplet which has been shown to be a good metallicity estimator for even the most metal-poor stars. The parameter estimation pipeline used on the survey data has trouble with accurately recovering the metallicities (they can be severely overestimated) and other parameters of the metal-poor stars. This is due to the lack of strong features in their spectra and sometimes humble signal-to-noise values. To cope with that we reanalyzed all metal-poor star spectra by measuring the equivalent widths of the CaII triplet lines. We devised a novel method employing Gaussian processes to model the continuum variations and also to account for the shallower and blended spectral lines that would otherwise add to the total equivalent width and lead to unwanted biases. New metallicity values for those stars were calibrated using the high resolution observations of the subset of stars and the available 8-band BVg'r'i'JHKS photometry. All sources of the uncertainty were taken into account which brought the final metallicity uncertainties to ~0.3dex, including for stars with lowest metal abundances. The study enabled us to discover many new very metal poor stars, several of which fall in the extremely metal-poor domain and some of which are possibly ultra metal-poor. For all stars in our sample

  12. Exposure to inhaled THM: comparison of continuous and event-specific exposure assessment for epidemiologic purposes.

    PubMed

    Thiriat, N; Paulus, H; Le Bot, B; Glorennec, P

    2009-10-01

    Trihalomethanes (THMs) (chloroform, bromoform, dibromochloromethane, and bromodichloromethane) are the most abundant by-products of chlorination. People are exposed to THMs through ingestion, dermal contact and inhalation. The objective of this study was to compare two methods for assessing THM inhalation: a direct method with personal monitors assessing continuous exposure and an indirect one with microenvironmental sampling and collection of time-activity data during the main event exposures: bathing, showering and swimming. This comparison was conducted to help plan a future epidemiologic study of the effects of THMs on the upper airways of children. 30 children aged from 4 to 10 years were included. They wore a 3M 3520 organic vapor monitor for 7 days. We sampled air in their bathrooms (during baths or showers) and in the indoor swimming pools they visited and recorded their time-activity patterns. We used stainless steel tubes full of Tenax to collect air samples. All analyses were performed with Gas Chromatography and Mass Spectrometry (GC-MS). Chloroform was the THM with the highest concentrations in the air of both bathrooms and indoor swimming pools. Its continuous and event exposure measurements were significantly correlated (r(s)=0.69 p<0.001). Continuous exposures were higher than event exposures, suggesting that the event exposure method does not take into account some influential microenvironments. In an epidemiologic study, this might lead to random exposure misclassification, thus underestimation of the risk, and reduced statistical power. The continuous exposure method was difficult to implement because of its poor acceptability and the fragility of the personal monitors. These two points may also reduce the statistical power of an epidemiologic study. It would be useful to test the advantages and disadvantages of a second sample in the home or of modeling the baseline concentration of THM in the home to improve the event exposure method. PMID

  13. Poor motor skills: a risk marker for bully victimization.

    PubMed

    Bejerot, Susanne; Plenty, Stephanie; Humble, Alice; Humble, Mats B

    2013-01-01

    Children who are clumsy are often bullied. Nevertheless, motor skills have been overlooked in research on bullying victimization. A total of 2,730 Swedish adults (83% females) responded to retrospective questions on bullying, their talents in physical education (i.e., coordination and balls skills) and school academics. Poor talents were used as indicators of poor gross motor skills and poor academic skills. A subset of participants also provided information on educational level in adulthood, childhood obesity, belonging to an ethic minority in school and socioeconomic status relative to schoolmates. A total of 29.4% of adults reported being bullied in school, and 18.4% reported having below average gross motor skills. Of those with below average motor skills, 48.6% were bullied in school. Below average motor skills in childhood were associated with an increased risk (OR 3.01 [95% CI: 1.97-4.60]) of being bullied, even after adjusting for the influence of lower socioeconomic status, poor academic performance, being overweight, and being a bully. Higher odds for bully victimization were also associated with lower socioeconomic status (OR 2.29 [95% CI: 1.45-3.63]), being overweight (OR 1.71 [95% CI: 1.18-2.47]) and being a bully (OR 2.18 [95% CI: 1.53-3.11]). The findings indicate that poor gross motor skills constitute a robust risk-marker for vulnerability for bully victimization. PMID:23784933

  14. MODEL DEVELOPMENT - EXPOSURE MODELS

    EPA Science Inventory

    Humans are exposed to mixtures of chemicals from multiple pathways and routes. These exposures may result from a single event or may accumulate over time if multiple exposure events occur. The traditional approach of assessing risk from a single chemical and a single route of e...

  15. IMMUNOASSAY HUMAN EXPOSURE STUDIES

    EPA Science Inventory

    The Human Exposure Research Branch has developed several enzyme-linked immunosorbent assay (ELISA) methods to support human exposure assessment studies. Immunoassays to detect low levels (<10 ng/mL) of chlorpyrifos in food, track-in dirt and house dust have been applied to sam...

  16. Environmental Exposures and Development

    PubMed Central

    Mattison, Donald R.

    2010-01-01

    Structured Abstract Purpose of Review Summarize recent studies exploring the relationship between paternal and maternal environmental exposures to chemicals before, at the time of and after conception to adverse developmental outcomes including; preterm birth, death, structural and functional abnormalities and growth restriction. Recent Findings Recent studies have demonstrated that human pregnancy and development is vulnerable to environmental exposures of the father and mother to chemical, biological and physical agents. Exposures associated with adverse developmental outcomes include; air and water pollution, chemicals in foods, occupational exposures, agricultural chemicals, metals, persistent and volatile organics. Developmental endpoints which are linked with these exposures include; growth restriction, functional abnormalities, structural abnormalities, preterm delivery and death. Despite this general understanding we still have incomplete knowledge concerning most exposures and the biological interactions responsible for impaired development and preterm delivery. Summary While single genes and individual chemical exposures are responsible for some instances of adverse pregnancy outcome or developmental disease, gene-environment interactions are responsible for the majority. These gene-environment interactions may occur in the father, mother, placenta or fetus suggesting that critical attention be given to maternal and paternal exposures and gene expression as they relate to the mode of action of the putative developmental toxicant both prior to and during pregnancy. PMID:20216314

  17. EXPOSURES TO ENVIRONMENTAL AGENTS

    EPA Science Inventory

    The planned interagency National Children's Study (NCS) will be studying a number of exposure issues in the context of health and well-being of infants and young children from pre-conception to age 21. Some of the important environmental exposure questions for NCS, include: how c...

  18. Avian inhalation exposure chamber

    DOEpatents

    Briant, J.K.; Driver, C.J.

    1992-05-05

    An exposure system is designed for delivering gaseous material ranging in particle size from 0.4 micrometers to 20.0 micrometers uniformly to the heads of experimental animals, primarily birds. The system includes a vertical outer cylinder and a central chimney with animal holding bottles connected to exposure ports on the vertical outer cylinder. 2 figs.

  19. Avian inhalation exposure chamber

    DOEpatents

    Briant, James K.; Driver, Crystal J.

    1992-01-01

    An exposure system for delivering gaseous material ranging in particle size from 0.4 micrometers to 20.0 micrometers uniformly to the heads of experimental animals, primarily birds. The system includes a vertical outer cylinder and a central chimney with animal holding bottles connected to exposure ports on the vertical outer cylinder.

  20. Exposure Corrections for Macrophotography

    ERIC Educational Resources Information Center

    Nikolic, N. M.

    1976-01-01

    Describes a method for determining the exposure correction factors in close-up photography and macrophotography. The method eliminates all calculations during picture-taking, and allows the use of a light meter to obtain the proper f-stop/exposure time combinations. (Author/MLH)

  1. Dermal exposure assessment techniques.

    PubMed

    Fenske, R A

    1993-12-01

    Exposure of the skin to chemical substances can contribute significantly to total dose in many workplace situations, and its relative importance will increase when airborne occupational exposure limits are reduced, unless steps to reduce skin exposure are undertaken simultaneously. Its assessment employs personal sampling techniques to measure skin loading rates, and combines these measurements with models of percutaneous absorption to estimate absorbed dose. Knowledge of dermal exposure pathways is in many cases fundamental to hazard evaluation and control. When the skin is the primary contributor to absorbed dose, dermal exposure measurements and biological monitoring play complementary roles in defining occupational exposures. Exposure normally occurs by one of three pathways: (i) immersion (direct contact with a liquid or solid chemical substance); (ii) deposition of aerosol or uptake of vapour through the skin; or (iii) surface contact (residue transfer from contaminated surfaces). Sampling methods fall into three categories: surrogate skin; chemical removal; and fluorescent tracers. Surface sampling represents a supplementary approach, providing an estimate of dermal exposure potential. Surrogate skin techniques involve placing a chemical collection medium on the skin. Whole-body garment samplers do not require assumptions relating to distribution, an inherent limitation of patch sampling. The validity of these techniques rests on the ability of the sampling medium to capture and retain chemicals in a manner similar to skin. Removal techniques include skin washing and wiping, but these measure only what can be removed from the skin, not exposure: laboratory removal efficiency studies are required for proper interpretation of data. Fluorescent tracer techniques exploit the visual properties of fluorescent compounds, and combined with video imaging make quantification of dermal exposure patterns possible, but the need to introduce a chemical substance (tracer

  2. Individual variation in p53 and Cip1 expression profiles in normal human fibroblast strains following exposure to high-let radiation

    SciTech Connect

    Carpenter, T.R.; Johnson, N.F.; Gilliland, F.D.

    1995-12-01

    Exposure to {alpha}-particles emitted by radon progeny appears to be the second-leading cause of lung cancer mortality. However, individual susceptibility to the carcinogenic effects of {alpha}-particles remains poorly characterized. Variation in susceptibility to cancer produced by certian classes of DNA-damaging chemicals is suspected to involve differences in metabolic activation and detoxication. Susceptibility to {alpha}-particle-induced cancer may involve variations in capacity or opportunity to repair DNA damage. Subtle variations in DNA repair capacity would more likely explain radon-related lung cancer susceptibility. The p53 tumor suppressor protein accumulates as a cellular response to DNA damage from ionizing radiation and regulates arrest in the G{sub 1} portion of the cell cycle. Arrest in G{sub 1} portion of the cell cycle. While upstream regulation of p53 protein stability is poorly understood, variations in the ability to accumulate p53 following DNA damage represent potential variations in lung cancer susceptibility related to radon progeny. Further, transcription of the cell-cycle regulatory gene Cip1 is regulated by p53 and increases following ionizing radiation. Therefore, variations in the expression of Cip1 following {alpha}-particle exposure may also be a susceptibility factor in radon-related lung cancers. The purpose of the present investigation was to measure p53 and Cip1 protein induction following {alpha}-particle exposure of fibroblast lines from nine individuals to determine if there were significant variations. The expression of Cip1 protein indicates the differences in response are biologically relevant.

  3. Factors contributing to poor treatment outcomes in childhood atopic dermatitis.

    PubMed

    Sokolova, Anna; Smith, Saxon D

    2015-11-01

    Atopic dermatitis (AD) is a chronic relapsing inflammatory disease of the skin and is the most common paediatric dermatological condition. While no cure is available, it can be treated effectively if adherence to a therapeutic plan is maintained. Poor adherence to treatment is common in AD and can lead to treatment failure, which has significant impacts on the patient, family and society. A comprehensive literature search was conducted to identify factors that contribute to poor treatment adherence in childhood AD and to identify possible strategies to remedy these. Identified factors leading to poor treatment adherence include: complexity of treatment regimen, lack of knowledge, impaired quality of life, dissatisfaction with treatment strategies, infrequent follow up, corticosteroid phobia and the use of complementary and alternative medicine. Effective strategies to increase treatment adherence include: caregiver education and utilisation of education adjuncts, optimisation of the patient/caregiver-clinician relationship, early and frequent follow up and improvement of patient and caregiver quality of life. PMID:25817780

  4. The temperatures of very metal-poor subdwarfs

    NASA Technical Reports Server (NTRS)

    Bell, R. A.

    1986-01-01

    The determination of ages for metal poor globular cluster stars using the relationship between stellar effective temperature and color, in order to transform isochrones from the L, Teff plane to the M(V), color plane is described. Estimates of the effective temperatures of metal-poor field subdwarfs deduced from the ratios of the integrated fluxes to the 12000 A fluxes of the 4 subdwarfs are in good agreement with published results. The stars are fainter than the models in the infrared, but the UV fluxes are in good agreement with model predictions.

  5. RR Lyrae Stars, Metal-Poor Stars, and the Galaxy

    NASA Astrophysics Data System (ADS)

    McWilliam, Andrew

    2011-08-01

    This online book contains the proceedings of a meeting on "RR Lyrae Stars, Metal-Poor Stars, and the Galaxy" held at the Carnegie Observatories, Pasadena, California, in January 2011, to honor the 80th year of George W. Preston III. The book comprises the 5th volume of the Carnegie Observatories Astrophysics Series, and contains reviews and research articles on recent developments in the area of RR Lyrae stars, including results from the Kepler space mission. Review and research articles on metal-poor stars and Galactic structure are also included.

  6. Turning a Poor Ion Channel into a Good Pump

    NASA Astrophysics Data System (ADS)

    Astumian, Dean

    2003-05-01

    We consider a membrane protein that can exist in two configurations, either one of which acts as a poor ion channel, allowing ions to slowly leak across the membrane from high to low elctrochemical potential. We show that random external fluctuations can provide the energy to turn this poor channel into a good pump that drives ion transport from low to high electrochemical potential. We discuss this result in terms of a gambling analogy, and point to possible implications for fields as far ranging as population biology, economics, and actuarial science.

  7. Alignments of the Dominant Galaxies in Poor Clusters

    NASA Astrophysics Data System (ADS)

    Fuller, Todd M.; West, Michael J.; Bridges, Terry J.

    1999-07-01

    We have examined the orientations of brightest cluster galaxies (BCGs) in poor MKW (Morgan, Kayser, and White) and AWM (Albert, White, and Morgan) clusters and find that, like their counterparts in richer Abell clusters, poor cluster BCGs exhibit a strong propensity to be aligned with the principal axes of their host clusters as well as the surrounding distribution of nearby (<=20 h-1 Mpc) Abell clusters. The processes responsible for dominant galaxy alignments are therefore independent of cluster richness. We argue that these alignments most likely arise from anisotropic infall of material into clusters along large-scale filaments.

  8. Major axis alignments of poor cluster dominant galaxies

    NASA Astrophysics Data System (ADS)

    Fuller, T.; West, M.; Bridges, T.

    1996-12-01

    The MKW and AWM poor clusters are very different environments from rich Abell clusters. We obtained images with the Jacobus Kapteyn Telescope of 21 brightest cluster members (BCM) of the MKW/AWM clusters and determined that the major axis of the BCMs exhibits alignments similar to those in rich cluster dominant galaxies. Specifically, the major axes of the poor cluster BCMs point to nearby (< 20 Mpc) Abell clusters. Using the Kolmolgorov-Smirnov test, we reject the hypothesis that the position angles are randomly distributed at the 97% confidence level. The processes responsible for dominant galaxy alignments are therefore independent of cluster richness.

  9. Shifts in dietary carbohydrate-lipid exposure regulate expression of the non-alcoholic fatty liver disease-associated gene PNPLA3/adiponutrin in mouse liver and HepG2 human liver cells

    PubMed Central

    Hao, Lei; Ito, Kyoko; Huang, Kuan-Hsun; Sae-tan, Sudathip; Lambert, Joshua D.; Ross, A. Catharine

    2014-01-01

    Objective Patatin-like phospholipase domain containing 3 (PNPLA3, adiponutrin) has been identified as a modifier of lipid metabolism. To better understand the physiological role of PNPLA3/adiponutrin, we have investigated its regulation in intact mice and human hepatocytes under various nutritional/metabolic conditions. Material/Methods PNPLA3 gene expression was determined by real-time PCR in liver of C57BL/6 mice after dietary treatments and in HepG2 cells exposed to various nutritional/metabolic stimuli. Intracellular lipid content was determined in HepG2 cells after siRNA-mediated knockdown of PNPLA3. Results In vivo, mice fed a high-carbohydrate (HC) liquid diet had elevated hepatic lipid content, and PNPLA3 mRNA and protein expression, compared to chow-fed mice. Elevated expression was completely abrogated by addition of unsaturated lipid emulsion to the HC diet. By contrast, in mice with high-fat diet-induced steatosis, Pnpla3 expression did not differ compared to low-fat fed mice. In HepG2 cells, Pnpla3 expression was reversibly suppressed by glucose depletion and increased by glucose refeeding, but unchanged by addition of insulin and glucagon. Several unsaturated fatty acids each significantly decreased Pnpla3 mRNA, similar to lipid emulsion in vivo. However, Pnpla3 knockdown in HepG2 cells did not alter total lipid content in high glucose- or oleic acid-treated cells. Conclusions Our results provide evidence that PNPLA3 expression is an early signal/signature of carbohydrate-induced lipogenesis, but its expression is not associated with steatosis per se. Under lipogenic conditions due to high-carbohydrate feeding, certain unsaturated fatty acids can effectively suppress both lipogenesis and PNPLA3 expression, both in vivo and in a hepatocyte cell line. PMID:25060692

  10. STATISTICAL MODELS FOR ESTIMATING THE HEALTH IMPACT OF AIR QUALITY REGULATIONS

    EPA Science Inventory

    Despite increasingly stringent national and local air quality regulations in the last three decades, adverse health effects associated with ambient exposure to air pollution persist. Not surprisingly, regulators, regulated industries, and the public are looking for evidence...

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

    PubMed

    Li, Lan; Liu, Jing-Cai; Lai, Fang-Nong; Liu, Huan-Qi; Zhang, Xi-Feng; Dyce, Paul W; Shen, Wei; Chen, Hong

    2016-01-01

    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. PMID:26845775

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

    PubMed Central

    Li, Lan; Liu, Jing-Cai; Lai, Fang-Nong; Liu, Huan-Qi; Zhang, Xi-Feng; Dyce, Paul W.; Shen, Wei; Chen, Hong

    2016-01-01

    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. PMID:26845775

  13. The burden of disease from pediatric lead exposure at hazardous waste sites in 7 Asian countries.

    PubMed

    Caravanos, Jack; Chatham-Stephens, Kevin; Ericson, Bret; Landrigan, Philip J; Fuller, Richard

    2013-01-01

    Identification and systematic assessment of hazardous wastes sites in low and middle-income countries has lagged. Hazardous waste problems are especially severe in lower income Asian countries where environmental regulations are non-existent, nonspecific or poorly enforced. In these countries extensive unregulated industrial development has created waste sites in densely populated urban areas. These sites appear to pose significant risks to public health, and especially to the health of children. To assess potential health risks from chemical contamination at hazardous waste sites in Asia, we assessed 679 sites. A total of 169 sites in 7 countries were classified as contaminated by lead. Eighty-two of these sites contained lead at levels high enough to produce elevated blood lead levels in surrounding populations. To estimate the burden of pediatric lead poisoning associated with exposure to lead in soil and water at these 82 lead-contaminated sites, we used standard toxicokinetic models that relate levels of lead in soil and water to blood lead levels in children. We calculated blood lead levels, and we quantified losses of intelligence (reductions in IQ scores) that were attributable to lead exposure at these sites. We found that 189,725 children in the 7 countries are at risk of diminished intelligence as a consequence of exposure to elevated levels of lead in water and soil at hazardous waste sites. Depending on choice of model, these decrements ranged from 4.94 to 14.96 IQ points. Given the restricted scope of this survey and the conservative estimation procedures employed, this number is almost certainly an underestimate of the full burden of disease. Exposure to toxic chemicals from hazardous waste sites is an important and heretofore insufficiently examined contributor to the Global Burden of Disease. PMID:22999658

  14. Repeated Ozone Exposure Exacerbates Insulin Resistance And Activates Innate Immune Response In Genetically Susceptible Mice

    PubMed Central

    Zhong, Jixin; Allen, Katryn; Rao, Xiaoquan; Ying, Zhekang; Braunstein, Zachary; Kankanala, Saumya R.; Xia, Chang; Wang, Xiaoke; Bramble, Lori A.; Wagner, James G.; Lewandowski, Ryan; Sun, Qinghua; Harkema, Jack R.; Rajagopalan, Sanjay

    2016-01-01

    Background Inhaled ozone (O3) has been demonstrated as a harmful pollutant and associated with chronic inflammatory diseases such as diabetes and vascular disorders. However, the underlying mechanisms by which O3 mediates harmful effects are poorly understood. Objectives To investigate the effect of O3 exposure on glucose intolerance, immune activation and underlying mechanisms in a genetically susceptible mouse model. Methods Diabetes-prone KK mice were exposed to filtered air (FA), or O3 (0.5 ppm) for 13 consecutive weekdays (4 h/day). Insulin tolerance test (ITT) was performed following the last exposure. Plasma insulin, adiponectin, and leptin were measured by ELISA. Pathologic changes were examined by H&E and oil-red-o staining. Inflammatory responses were detected using flow cytometry and real-time PCR. Results KK mice exposed to O3 displayed an impaired insulin response. Plasma insulin and leptin levels were reduced in O3-exposed mice. Three-week exposure to O3 induced lung inflammation and increased monocytes/macrophages in both blood and visceral adipose tissue. Inflammatory monocytes/macrophages increased both systemically and locally. CD4+ T cell activation was also enhanced by the exposure of O3 although the relative percentage of CD4+ T cell decreased in blood and adipose tissue. Multiple inflammatory genes including CXCL-11, IFN-γ, TNFα, IL-12, and iNOS were up-regulated in visceral adipose tissue. Furthermore, the expression of oxidative stress-related genes such as Cox4, Cox5a, Scd1, Nrf1, and Nrf2, increased in visceral adipose tissue of O3-exposed mice. Conclusions Repeated O3 inhalation induces oxidative stress, adipose inflammation and insulin resistance. PMID:27240593

  15. Effects of Classroom Acoustics and Self-Reported Noise Exposure on Teachers' Well-Being

    ERIC Educational Resources Information Center

    Kristiansen, Jesper; Persson, Roger; Lund, Soren Peter; Shibuya, Hitomi; Nielsen, Per Moberg

    2013-01-01

    Beyond noise annoyance and voice problems, little is known about the effects that noise and poor classroom acoustics have on teachers' health and well-being. The aim of this field study was therefore to investigate the effects of perceived noise exposure and classroom reverberation on measures of well-being. Data on self-reported noise exposure,…

  16. AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    EPA Science Inventory

    The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...

  17. The Effect of Exposure Duration on Visual Character Identification in Single, Whole, and Partial Report

    ERIC Educational Resources Information Center

    Petersen, Anders; Andersen, Tobias S.

    2012-01-01

    The psychometric function of single-letter identification is typically described as a function of stimulus intensity. However, the effect of stimulus exposure duration on letter identification remains poorly described. This is surprising because the effect of exposure duration has played a central role in modeling performance in whole and partial…

  18. Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs.

    PubMed

    Censi, Roberta; Di Martino, Piera

    2015-01-01

    Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they can be a challenge to ensure physicochemical stability for the entire shelf life of the drug product. Since clinical failures of polymorph drugs have not been uncommon, and some of them have been entirely unexpected, the Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) has required preliminary and exhaustive screening studies to identify and characterize all the polymorph crystal forms for each drug. In the past, the polymorphism of many drugs was detected fortuitously or through manual time consuming methods; today, drug crystal engineering, in particular, combinatorial chemistry and high-throughput screening, makes it possible to easily and exhaustively identify stable polymorphic and/or hydrate/dehydrate forms of poorly soluble drugs, in order to overcome bioavailability related problems or clinical failures. This review describes the concepts involved, provides examples of drugs characterized by poor solubility for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations. PMID:26501244

  19. 29 CFR 1926.52 - Occupational noise exposure.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 8 2011-07-01 2011-07-01 false Occupational noise exposure. 1926.52 Section 1926.52 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Occupational Health and Environmental Controls § 1926.52 Occupational...

  20. Occupational exposure in MRI.

    PubMed

    McRobbie, D W

    2012-04-01

    This article reviews occupational exposure in clinical MRI; it specifically considers units of exposure, basic physical interactions, health effects, guideline limits, dosimetry, results of exposure surveys, calculation of induced fields and the status of the European Physical Agents Directive. Electromagnetic field exposure in MRI from the static field B(0), imaging gradients and radiofrequency transmission fields induces electric fields and currents in tissue, which are responsible for various acute sensory effects. The underlying theory and its application to the formulation of incident and induced field limits are presented. The recent International Commission on Non-Ionizing Radiation Protection (ICNIRP) Bundesministerium für Arbeit und Soziales and Institute of Electrical and Electronics Engineers limits for incident field exposure are interpreted in a manner applicable to MRI. Field measurements show that exposure from movement within the B(0) fringe field can exceed ICNIRP reference levels within 0.5 m of the bore entrance. Rate of change of field dB/dt from the imaging gradients is unlikely to exceed the new limits, although incident field limits can be exceeded for radiofrequency (RF) exposure within 0.2-0.5 m of the bore entrance. Dosimetric surveys of routine clinical practice show that staff are exposed to peak values of 42 ± 24% of B(0), with time-averaged exposures of 5.2 ± 2.8 mT for magnets in the range 0.6-4 T. Exposure to time-varying fields arising from movement within the B(0) fringe resulted in peak dB/dt of approximately 2 T s(-1). Modelling of induced electric fields from the imaging gradients shows that ICNIRP-induced field limits are unlikely to be exceeded in most situations; however, movement through the static field may still present a problem. The likely application of the limits is discussed with respect to the reformulation of the European Union (EU) directive and its possible implications for MRI. PMID:22457400