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Sample records for poorly regulated exposure

  1. 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…

  2. 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.

  3. 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.

  4. Environmental radiation exposure: Regulation, monitoring, and assessment

    SciTech Connect

    Chen, S.Y.; Yu, C.; Hong, K.J.

    1991-01-01

    Radioactive releases to the environment from nuclear facilities constitute a public health concern. Protecting the public from such releases can be achieved through the establishment and enforcement of regulatory standards. In the United States, numerous standards have been promulgated to regulate release control at nuclear facilities. Most recent standards are more restrictive than those in the past and require that radioactivity levels be as low as reasonably achievable (ALARA). Environmental monitoring programs and radiological dose assessment are means of ensuring compliance with regulations. Environmental monitoring programs provide empirical information on releases, such as the concentrations of released radioactivity in environmental media, while radiological dose assessment provides the analytical means of quantifying dose exposures for demonstrating compliance.

  5. Parental exposure to pesticides and poor clutch viability in American alligators.

    PubMed

    Rauschenberger, R Heath; Wiebe, Jon J; Sepúlveda, Maria S; Scarborough, Janet E; Gross, Timothy S

    2007-08-01

    In central Florida, alligators (Alligator mississippiensis) inhabiting lakes contaminated with organochlorine pesticides (OCPs) produce eggs that have high OCP concentrations and low clutch viability (proportion of eggs in a clutch that yield a live hatchling) compared to those from less contaminated lakes (reference lakes). However, a clear dose-response relationship has not been established between OCPs and poor clutch viability. In order to better elucidate a cause and effect relationship between OCP exposure and clutch viability, we conducted concurrent field and laboratory studies. Our field study reaffirmed that eggs of wild alligators from OCP-contaminated lakes and wetlands continue to have lower clutch viability and higher OCP burdens than eggs from reference lakes. Our field study also demonstrated that OCP egg burdens were strongly correlated with clutch viability for some of the OCP-contaminated sites, but not all. To better test causal relationships, a parental exposure study was conducted using captive adult alligators. Our laboratory study demonstrated that dietary exposure of captive alligators to an ecologically relevant OCP mixture caused alligators to produce eggs with higher OCP burdens and reduced clutch viability, as compared to the captive-control population. The experimentally induced egg burdens and clutch viability reductions were similar to those of wild alligators from OCP-contaminated sites. Our field and laboratory results suggest parental OCP exposure may be contributing to low clutch viability in wild alligators inhabiting OCP-contaminated habitats, raising some concern for endangered crocodilians living in OCP-contaminated habitats.

  6. Regulation of occupational exposures in China.

    PubMed

    Wong, Otto

    2003-10-01

    The recent passage of the Occupational Diseases Prevention and Control Act of 2002 (ODPCAct) in China and the new occupational exposure limits signify the Chinese government's commitment to improve the environment of the workplace and to eradicate preventable occupational diseases. The effectiveness of the ODPCAct, however, will depend on not only implementation and enforcement but also education and communication. For large industrial facilities, implementation of the new regulations can be enforced with periodic monitoring and inspections. The difficulty will come from small makeshift or crudely converted workshops in villages and small towns in rural areas. The challenge will be to reach out to these small workshop owners and workers, i.e., to communicate and inform them about the newly promulgated regulations, the business owners' legal responsibility and liability, and the workers' right to a safe workplace. Attention and resources should be focused on educating both shop owners and workers about the hazards of the chemicals that they use, basic requirements for a safe workplace, preventive measures, and controls to reduce exposures.

  7. 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

  8. 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…

  9. Using behavior change to reduce child lead exposure in resource-poor settings: a formative study.

    PubMed

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

    2014-12-01

    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 chose the behaviors they wanted to try and then performed them in their homes over 4 weeks. Researchers interviewed them at the end of the month to understand their experience of trying out the behaviors. The modified behaviors offered to each participant were as follows: cleaning window sills with detergent and water, cleaning window sills more frequently, mopping floors with two buckets (one with soapy water for washing and one with clean water for rinsing), mopping floors more frequently, dusting surfaces with detergent and water and dusting surfaces more frequently. Participants found cleaning window sills with soap and water and cleaning them more often the most acceptable and feasible of behavior modifications. Environmental samples showed a significant reduction in lead dust on window sills. These findings can assist in the development of acceptable and feasible medium-term interventions to reduce childhood lead exposure in resource-poor settings until more robust health policies are implemented.

  10. 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

  11. 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…

  12. 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…

  13. HYOU1, Regulated by LPLUNC1, Is Up-Regulated in Nasopharyngeal Carcinoma and Associated with Poor Prognosis

    PubMed Central

    Zhou, Yujuan; Liao, Qianjin; Li, Xiayu; Wang, Hui; Wei, Fang; Chen, Jie; Yang, Jing; Zeng, Zhaoyang; Guo, Xiaofang; Chen, Pan; Zhang, Wenling; Tang, Ke; Li, Xiaoling; Xiong, Wei; Li, Guiyuan

    2016-01-01

    Objective: This study aims to investigate the roles and mechanisms of long palate, lung and nasal epithelium clone 1 (LPLUNC1) in nasopharyngeal carcinoma (NPC). Methods: The two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-TOF-MS/MS) was applied to identify differentially expressed proteins after over-expressing LPLUNC1 in NPC cells. The qRT-PCR and Western Blot were used to further validate differentially expression of Hypoxia up-regulated 1 (HYOU1). We also applied immunohistochemistry (IHC) to validate the expression of HYOU1 protein in NPC tissues. Results: Totally 44 differentially expressed proteins were identified, among which 19 proteins were up-regulated and 25 proteins were down-regulated. Function annotation indicated that these proteins were involved in molecular chaperone, cytoskeleton, metabolism and signal transduction. It was shown that the expression of HYOU1 both at mRNA level and protein level was up-regulated significantly in NPC tissues, and HYOU1 protein expression was positively correlated with clinical staging and metastasis of NPC. Kaplan-Meier survival curves showed that high expression of HYOU1 protein in NPC patients had shorter progression-free survival (PFS) and overall survival (OS). COX multivariate regression analysis further indicated that over-expressed HYOU1 was one of the predictors for poor prognosis in NPC patients. Conclusion: Through regulating proteins in different pathways, LPLUNC1 may inhibit the growth of NPC through participating in cell metabolism, proliferation, transcription and signaling transduction. HYOU1 can be regarded as potential molecular biomarker for progression and prognosis of NPC. PMID:26918051

  14. Oropharyngeal squamous cell carcinoma (OPSCCA) in the veteran population is associated with traditional carcinogen exposure and poor clinical outcomes

    PubMed Central

    Sandulache, Vlad C.; Hamblin, John; Lai, Syeling; Pezzi, Todd; Skinner, Heath D.; Khan, Numan A.; Dioun, Shayan M.; Hartman, Christine; Kramer, Jennifer; Chiao, Elizabeth; Zhou, Xiaodong; Zevallos, Jose P.

    2014-01-01

    Background A significant fraction of OPSCCA cases is associated with traditional carcinogens; in these patients treatment response and clinical outcomes remain poor. Methods We evaluated patient, tumor and treatment characteristics for 200 veterans with OPSCCA treated at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) between 2000 and 2012. Results Most patients (77%) were white and heavy smokers. Twenty seven patients required tracheostomy and 63 required gastrostomy placement during treatment. Overall survival at 5 years was 40%.. Survival was impacted by T stage, treatment intensity, completion of treatment and p16 tumor status. Almost 30% of patients were unable to complete a treatment regimen consistent with NCCN guidelines. Conclusions OPSCCA in veterans is associated with traditional carcinogens and poor clinical outcomes. Despite heavy smoking exposure, p16 tumor status significantly impacts survival. Careful consideration must be given to improving treatment paradigms for this cohort given their limited tolerance for treatment escalation. PMID:24801106

  15. 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.

  16. Prenatal Substance Exposure and Child Self-Regulation: Pathways to Risk and Protection

    PubMed Central

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

    2015-01-01

    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. Prenatal cocaine exposure and prolonged focus attention. Poor infant information processing ability or precocious maturation of attentional systems?

    PubMed

    Chiriboga, Claudia A; Starr, Denise; Kuhn, Louise; Wasserman, Gail A

    2009-01-01

    In experimental models, prenatal cocaine exposure has been found to perturb monoaminergic development of systems implicated in modulating attention. To determine whether prenatal cocaine exposure affects infant attention, we assessed visual recognition memory and focused attention during free play. We enrolled at birth 380 infants, 113 cocaine exposed, using multiple biomarkers to assess drug exposure. Behavior was videotaped and coded off-line for sustained looking time (i.e. focused attention), banging and intrusion. Prenatal cocaine exposure was not associated with visual recognition memory, but was significantly associated with longer sustained looking times (average focused attention) at ages 6 months (p = 0.02) and 12 months (p = 0.04) in analyses that adjusted for variables, including maternal intelligence, education, depressive scores and other exposures (alcohol, tobacco and marijuana). Cocaine-exposed infants at age 12 months also spent significantly less time in banging activity (p = 0.02) after adjusting for confounding variables. This finding was not explained through cocaine effects on motor development, neurological findings or time spent in focused attention. Prenatal cocaine exposure was significantly associated with longer periods of sustained looking or focused attention in infancy, a finding that could interpreted as a measure of poor processing efficiency, or alternatively as precocious maturation of attentional systems. Either interpretation has implications for later cognitive development. Lower banging activity among cocaine exposed was not explained through cocaine effects on motor development or neurological findings, suggesting that activity level itself is diminished in these infants. Whether focused attention findings impact long term development awaits further study.

  18. Novel dosing strategies increase exposures of the potent antituberculosis drug rifapentine but are poorly tolerated in healthy volunteers.

    PubMed

    Dooley, Kelly E; 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 no

  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. Federal government regulation of occupational skin exposure in the USA.

    PubMed

    Boeniger, Mark F; Ahlers, Heinz W

    2003-06-01

    There are at least 14 federal regulations and three agencies that are involved in the regulation of occupational skin exposures in the USA. The Environmental Protection Agency (EPA) requires the reporting of health effects information on chemicals, and such information is used to assess the risks of human and environmental exposure. The health effects information and any resulting risk assessments are generally available to the public. A fair amount of this information relates to skin irritation, sensitization, and dermal absorption. The EPA can require the submission of new data necessary for it to carry out its risk assessments, and has the authority to ban hazardous chemicals for certain uses. The Food and Drug Administration (FDA) regulates the correct labeling of cosmetics and requires safety and efficacy data on new products that are claimed to have preventive or health benefits. Commercial distribution of topical skin-care and protection products, therefore, can be potentially scrutinized by the FDA, which can control the use of hazardous chemicals in such products. The Occupational Safety and Health Administration (OSHA) has the most direct contact with workplaces through its field inspection compliance activity, which is directed at the reduction of workplace injuries and illnesses. Our analysis suggests that although considerable amounts of health effects information is generated and available, such information may not always be adequately conveyed to the end users of chemical products. In addition, the most effective and practical means of preventing exposure is often not apparent or generally known. Current regulations may have created a reliance on use of chemical protective equipment that may not always be the best approach to protecting workers. Lack of performance criteria that are measurable has hampered industry from objectively assessing skin exposures. This lack of performance criteria or guidance has also hindered the implementation of

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

    PubMed

    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.

  3. Up-Regulated Expression of SPRY4-IT1 Predicts Poor Prognosis in Colorectal Cancer

    PubMed Central

    Tan, Wenlong; Song, Zi-zheng; Xu, Qunfang; Qu, Xinyan; Li, Zhen; Wang, Yu; Yu, Qun; Wang, Shengqi

    2017-01-01

    Background Long non-coding RNA SPRY4 intronic transcript 1 (lncRNA SPRY4-IT1) has been reported to be associated with the progression of several cancers, but its expression level in colorectal cancer (CRC) has rarely been reported. The purpose of this study was to estimate the clinical significance of SPRY4-IT1 in CRC. Material/Methods The relative expression levels of SPRY4-IT1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in diseased tissues and the adjacent normal tissues of 106 CRC patients. Chi-square method was used to evaluate the association between SPRY4-IT1 expression and the clinical features. Additionally, we assessed the overall survival at different expression levels of SPRY4-IT1 using Kaplan-Meier method. The prognostic significance of SPRY4-IT1 was estimated by Cox regression analysis. Results Up-regulated level of SPRY4-IT1 was detected in pathologic tissues of CRC patients compared with adjacent normal tissues (P=0.000). The relative expression of SPRY4-IT1 was associated with the tumor size, the depth of invasion, lymph node invasion, distant invasion, and tumor stage (P<0.05). Patients with high expression of SPRY4-IT1 had poor overall survival compared with those with high level (39.3 vs. 49.3 months, log-rank test, P=0.016). Cox regression analysis showed that SPRY4-IT1 could act as an independent prognostic factor in CRC (HR=2.341, 95% CI=1.136–4.826, P=0.021). Conclusions SPRY4-IT1 might be associated with tumorigenesis and progression of CRC, and it may be a promising biomarker for prognosis in patients with CRC. PMID:28099409

  4. 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

  5. Transformation of poorly water-soluble drugs into lipophilic ionic liquids enhances oral drug exposure from lipid based formulations.

    PubMed

    Sahbaz, Yasemin; Williams, Hywel D; Nguyen, Tri-Hung; Saunders, Jessica; Ford, Leigh; Charman, Susan A; Scammells, Peter J; Porter, Christopher J H

    2015-06-01

    Absorption after oral administration is a requirement for almost all drug products but is a challenge for drugs with intrinsically low water solubility. Here, the weakly basic, poorly water-soluble drugs (PWSDs) itraconazole, cinnarizine, and halofantrine were converted into lipophilic ionic liquids to facilitate incorporation into lipid-based formulations and integration into lipid absorption pathways. Ionic liquids were formed via metathesis reactions of the hydrochloride salt of the PWSDs with a range of lipophilic counterions. The resultant active pharmaceutical ingredient-ionic liquids (API-ILs) were liquids or low melting point solids and either completely miscible or highly soluble in lipid based, self-emulsifying drug delivery systems (SEDDS) comprising mixtures of long or medium chain glycerides, surfactants such as Kolliphor-EL and cosolvents such as ethanol. They also readily incorporated into the colloids formed in intestinal fluids during lipid digestion. Itraconazole docusate or cinnarizine decylsulfate API-ILs were subsequently dissolved in long chain lipid SEDDS at high concentration, administered to rats and in vivo exposure assessed. The data were compared to control formulations based on the same SEDDS formulations containing the same concentrations of drug as the free base, but in this case as a suspension (since the solubility of the free base in the SEDDS was much lower than the API-ILs). For itraconazole, comparison was also made to a physical mixture of itraconazole free base and sodium docusate in the same SEDDS formulation. For both drugs plasma exposure was significantly higher for the API-IL containing formulations (2-fold for cinnarizine and 20-fold for itraconazole), when compared to the suspension formulations (or the physical mixture in the case of itraconazole) at the same dose. The liquid SEDDS formulations, made possible by the use of the API-ILs, also provide advantages in dose uniformity, capsule filling, and stability compared

  6. Exposure to Cocaine Regulates Inhibitory Synaptic Transmission in the Nucleus Accumbens

    PubMed Central

    Otaka, Mami; Ishikawa, Masago; Lee, Brian R.; Liu, Lei; Neumann, Peter A.; Cui, Ranji; Huang, Yanhua; Schlüter, Oliver M.; Dong, Yan

    2013-01-01

    Medium spiny neurons (MSNs) within the nucleus accumbens shell (NAc) function to gate and prioritize emotional/motivational arousals for behavioral output. The neuronal output NAc MSNs is mainly determined by the integration of membrane excitability and excitatory/inhibitory synaptic inputs. Whereas cocaine-induced alterations at excitatory synapses and membrane excitability have been extensively examined, the overall functional output of NAc MSNs following cocaine exposure still poorly defined because little is known about whether inhibitory synaptic input to these neurons is affected by cocaine. Here, our results demonstrate multidimensional alterations at inhibitory synapses in NAc neurons following cocaine self-administration in rats. Specifically, the amplitude of miniature (m) inhibitory postsynaptic currents (IPSCs) was decreased after 21-d withdrawal from 5-d cocaine self-administration. Upon re-exposure to cocaine after 21-day withdrawal, whereas the amplitude of mIPSCs remained down-regulated, the frequency became significantly higher. Furthermore, the reversal potential of IPSCs, which was not significantly altered during withdrawal, became more hyperpolarized upon cocaine re-exposure. Moreover, the relative weight of excitatory and inhibitory inputs to NAc MSNs was significantly decreased after 1-d cocaine withdrawal, increased after 21-d withdrawal, and returned to the basal level upon cocaine re-exposure after 21-d withdrawal. These results, taken together with previous results showing cocaine-induced adaptations at excitatory synapses and intrinsic membrane excitability of NAc MSNs, may provide a relatively thorough picture of the functional state of NAc MSNs following cocaine exposure. PMID:23595733

  7. 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.

  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.

  9. MC1R is a potent regulator of PTEN after UV exposure in melanocytes.

    PubMed

    Cao, Juxiang; Wan, Lixin; Hacker, Elke; Dai, Xiangpeng; Lenna, Stefania; Jimenez-Cervantes, Celia; Wang, Yongjun; Leslie, Nick R; Xu, George X; Widlund, Hans R; Ryu, Byungwoo; Alani, Rhoda M; Dutton-Regester, Ken; Goding, Colin R; Hayward, Nicholas K; Wei, Wenyi; Cui, Rutao

    2013-08-22

    The individuals carrying melanocortin-1 receptor (MC1R) variants, especially those associated with red hair color, fair skin, and poor tanning ability (RHC trait), are more prone to melanoma; however, the underlying mechanism is poorly defined. Here, we report that UVB exposure triggers phosphatase and tensin homolog (PTEN) interaction with wild-type (WT), but not RHC-associated MC1R variants, which protects PTEN from WWP2-mediated degradation, leading to AKT inactivation. Strikingly, the biological consequences of the failure of MC1R variants to suppress PI3K/AKT signaling are highly context dependent. In primary melanocytes, hyperactivation of PI3K/AKT signaling leads to premature senescence; in the presence of BRAF(V600E), MC1R deficiency-induced elevated PI3K/AKT signaling drives oncogenic transformation. These studies establish the MC1R-PTEN axis as a central regulator for melanocytes' response to UVB exposure and reveal the molecular basis underlying the association between MC1R variants and melanomagenesis.

  10. Down-regulation of β-arrestin2 promotes tumour invasion and indicates poor prognosis of hepatocellular carcinoma

    PubMed Central

    Sun, Wu-Yi; Hu, Shan-Shan; Wu, Jing-Jing; Huang, Qiong; Ma, Yang; Wang, Qing-Tong; Chen, Jing-Yu; Wei, Wei

    2016-01-01

    β-arrestins, including β-arrestin1 and β-arrestin2, are multifunctional adaptor proteins. β-arrestins have recently been found to play new roles in regulating intracellular signalling networks associated with malignant cell functions. Altered β-arrestin expression has been reported in many cancers, but its role in hepatocellular carcinoma (HCC) is not clear. We therefore examined the roles of β-arrestins in HCC using an animal model of progressive HCC, HCC patient samples and HCC cell lines with stepwise metastatic potential. We demonstrated that β-arrestin2 level, but not β-arrestin1 level, decreased in conjunction with liver tumourigenesis in a mouse diethylnitrosamine-induced liver tumour model. Furthermore, β-arrestin2 expression was reduced in HCC tissues compared with noncancerous tissues in HCC patients. β-arrestin2 down-regulation in HCC was significantly associated with poor patient prognoses and aggressive pathologic features. In addition, our in vitro study showed that β-arrestin2 overexpression significantly reduced cell migration and invasion in cultured HCC cells. Furthermore, β-arrestin2 overexpression up-regulated E-cadherin expression and inhibited vimentin expression and Akt activation. These results suggest that β-arrestin2 down-regulation increases HCC cell migration and invasion ability. Low β-arrestin2 expression may be indicative of a poor prognosis or early cancer recurrence in patients who have undergone surgery for HCC. PMID:27759077

  11. 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…

  12. Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT.

    PubMed

    He, Zhen-Yu; Wu, San-Gang; Peng, Fang; Zhang, Qun; Luo, Ying; Chen, Ming; Bao, Yong

    2017-02-01

    Triple-negative breast cancer (TNBC) was regarded as the most aggressive and mortal subtype of breast cancer (BC) since the molecular subtype system has been established. Abundant studies have revealed that epithelial-mesenchymal transition (EMT) played a pivotal role during breast cancer metastasis and progression, especially in TNBC. Herein, we showed that inhibition the expression of replication factor C subunit 3 (RFC3) significantly attenuated TNBC metastasis and progression, which was associated with EMT signal pathway. In TNBC cells, knockdown of RFC3 can down-regulate mesenchymal markers and up-regulate epithelial markers, significantly attenuated cell proliferation, migration and invasion. Additionally, silencing RFC3 expression can decrease nude mice tumor volume, weight and relieve lung metastasis in vivo. Furthermore, we also demonstrated that overexpression of RFC3 in TNBC showed increased metastasis, progression and poor prognosis. We confirmed all of these results by immunohistochemistry analysis in 127 human TNBC tissues and found that RFC3 expression was significantly associated with poor prognosis in TNBC. Taken all these findings into consideration, we can conclude that up-regulation of RFC3 promotes TNBC progression through EMT signal pathway. Therefore, RFC3 could be an independent prognostic factor and therapeutic target for TNBC.

  13. 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.

  14. 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

  15. Addiction-Related Gene Regulation: Risks of Exposure to Cognitive Enhancers vs. Other Psychostimulants

    PubMed Central

    Steiner, Heinz; Van Waes, Vincent

    2012-01-01

    The psychostimulants methylphenidate (Ritalin, Concerta), amphetamine (Adderall), and modafinil (Provigil) are widely used in the treatment of medical conditions such as attention-deficit hyperactivity disorder and narcolepsy and, increasingly, as “cognitive enhancers” by healthy people. The long-term neuronal effects of these drugs, however, are poorly understood. A substantial amount of research over the past 2 decades has investigated the effects of psychostimulants such as cocaine and amphetamines on gene regulation in the brain because these molecular changes are considered critical for psychostimulant addiction. This work has determined in some detail the neurochemical and cellular mechanisms that mediate psychostimulant-induced gene regulation and has also identified the neuronal systems altered by these drugs. Among the most affected brain systems are corticostriatal circuits, which are part of cortico-basal ganglia-cortical loops that mediate motivated behavior. The neurotransmitters critical for such gene regulation are dopamine in interaction with glutamate, while other neurotransmitters (e.g., serotonin) play modulatory roles. This review presents (1) an overview of the main findings on cocaine- and amphetamine-induced gene regulation in corticostriatal circuits in an effort to provide a cellular framework for (2) an assessment of the molecular changes produced by methylphenidate, medical amphetamine (Adderall), and modafinil. The findings lead to the conclusion that protracted exposure to these cognitive enhancers can induce gene regulation effects in corticostriatal circuits that are qualitatively similar to those of cocaine and other amphetamines. These neuronal changes may contribute to the addiction liability of the psychostimulant cognitive enhancers. PMID:23085425

  16. The relationship between subjective sleep disturbance, sleep quality, and emotion regulation difficulties in a sample of college students reporting trauma exposure.

    PubMed

    Pickett, Scott M; Barbaro, Nicole; Mello, David

    2016-01-01

    Sleep disturbance and poor sleep quality has been associated with trauma exposure and posttraumatic stress disorder (PTSD) symptoms; however, the associated emotional consequences of sleep disturbance have not been examined within this context (i.e., emotional reactivity, emotion modulation). The current study examined the relationship between sleep disturbance, poor sleep quality, and emotion regulation difficulties. In a sample of college students reporting exposure to at least 1 traumatic event, online survey methodology was used to assess PTSD symptom severity (PTSS), sleep disturbances, including PTSD-specific sleep disturbances, and emotion regulation difficulties. After controlling for PTSS, sleep disturbance and poor sleep quality domains were related to both global and specific difficulties in emotion regulation domains. The findings suggest that sleep disturbance and emotion regulation difficulties associated with PTSD may not be a mere extension of the clinical picture of PTSD. Sleep disturbances following trauma exposure may contribute to emotion regulation difficulties and exacerbate negative consequences. Future research should examine the effects of treatments that simultaneously address sleep disturbances and PTSD symptoms on emotion regulation processes.

  17. FRZB up-regulation is correlated with hepatic metastasis and poor prognosis in colon carcinoma patients with hepatic metastasis.

    PubMed

    Shen, Yanping; Zhang, Fang; Lan, Huanrong; Chen, Ke; Zhang, Qi; Xie, Guoming; Teng, Lisong; Jin, Ketao

    2015-01-01

    Frizzled-related protein (FRZB) was up-regulated in hepatic metastasis samples compared with primary colon cancer samples in our previous work. However, the clinical relevance of FRZB in colon cancer hepatic metastasis remains uncertain. The aim of this study was to assess the prognostic value of FRZB in patients with colon carcinoma hepatic metastasis after hepatic resection. FRZB expression was evaluated by immunohistochemistry in formalin-fixed paraffin embedded (FFPE) primary colon carcinoma and paired hepatic metastasis tissues from 136 patients with liver metastasis from colon carcinoma that underwent hepatic resection. The relation between FRZB expression and clinicopathologic factors and long-term prognosis in these 136 patients was retrospectively examined. The prognostic significance of negative or positive FRZB expression in colon carcinoma hepatic metastasis was assessed using Kaplan-Meier survival analysis and log-rank tests. Positive expression of FRZB was correlated with liver metastasis of colon cancer. Univariate analysis indicated significantly worse overall survival (OS) for patients with a positive FRZB expression in colon carcinoma hepatic metastasis than for patients with a negative FRZB expression. Multivariate analysis showed positive-FRZB in colon carcinoma hepatic metastasis to be an independent prognostic factor for OS after hepatic resection (P = 0.001). Positive expression of FRZB was statistically significantly associated with poor prognosis of patients with colon carcinoma hepatic metastasis. FRZB could be a novel predictor for poor prognosis of patients with colon carcinoma hepatic metastasis after hepatic resection.

  18. miR-135b, a key regulator of malignancy, is linked to poor prognosis in human myxoid liposarcoma

    PubMed Central

    Nezu, Y; Hagiwara, K; Yamamoto, Y; Fujiwara, T; Matsuo, K; Yoshida, A; Kawai, A; Saito, T; Ochiya, T

    2016-01-01

    Myxoid/round cell (RC) liposarcomas (MLS) were originally classified into two distinct populations based on histological differences; a myxoid component and a RC component. It is notable that, depending on an increase of the RC component, the prognosis significantly differs. Hence, the RC component is associated with metastasis and poor prognosis. However, the molecular mechanisms that contribute to the malignancy of the RC component still remain largely unknown. Here, we report microRNA-135b (miR-135b), a key regulator of the malignancy, highly expressed in the RC component and promoting MLS cell invasion in vitro and metastasis in vivo through the direct suppression of thrombospondin 2 (THBS2). Decreased THBS2 expression by miR-135b increases the total amount of matrix metalloproteinase 2 (MMP2) and influences cellular density and an extracellular matrix structure, thereby resulting in morphological change in tumor. The expression levels of miR-135b and THBS2 significantly correlated with a poor prognosis in MLS patients. Overall, our study reveals that the miR-135b/THBS2/MMP2 axis is tightly related to MLS pathophysiology and has an important clinical implication. This work provides noteworthy evidence for overcoming metastasis and improving patient outcomes, and sheds light on miR-135b and THBS2 as novel molecular targets for diagnosis and therapy in MLS. PMID:27157622

  19. 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.

  20. 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

  1. S100A6 Overexpression Is Associated with Poor Prognosis and Is Epigenetically Up-Regulated in Gastric Cancer

    PubMed Central

    Wang, Xiao-Hong; Zhang, Lian-Hai; Zhong, Xi-Yao; Xing, Xiao-Fang; Liu, Yi-Qiang; Niu, Zhao-Jian; Peng, Yong; Du, Hong; Zhang, Gui-Guo; Hu, Ying; Liu, Ni; Zhu, Yu-Bing; Ge, Shao-Hua; Zhao, Wei; Lu, Ai-Ping; Li, Ji-You; Ji, Jia-Fu

    2010-01-01

    S100A6 has been implicated in a variety of biological functions as well as tumorigenesis. In this study, we investigated the expression status of S100A6 in relation to the clinicopathological features and prognosis of patients with gastric cancer and further explored a possible association of its expression with epigenetic regulation. S100A6 expression was remarkably increased in 67.5% of gastric cancer tissues as compared with matched noncancerous tissues. Statistical analysis demonstrated a clear correlation between high S100A6 expression and various clinicopathological features, such as depth of wall invasion, positive lymph node involvement, liver metastasis, vascular invasion, and tumor-node metastasis stage (P < 0.05 in all cases), as well as revealed that S100A6 is an independent prognostic predictor (P = 0.026) significantly related to poor prognosis (P = 0.0004). Further exploration found an inverse relationship between S100A6 expression and the methylation status of the seventh and eighth CpG sites in the promoter/first exon and the second to fifth sites in the second exon/second intron. In addition, the level of histone H3 acetylation was found to be significantly higher in S100A6-expressing cancer cells. After 5-azacytidine or trichostatin A treatment, S100A6 expression was clearly increased in S100A6 low-expressing cells. In conclusion, our results suggested that S100A6 plays an important role in the progression of gastric cancer, affecting patient prognosis, and is up-regulated by epigenetic regulation. PMID:20581057

  2. Regulation of adenosine transport by acute and chronic ethanol exposure

    SciTech Connect

    Nagy, L.E.; Casso, D.; Diamond, I.; Gordon, A.S. )

    1989-02-09

    Chronic exposure to ethanol results in a desensitization of adenosine receptor-stimulated cAMP production. Since adenosine is released by cells and is known to desensitize its own as well as other receptors, it may be involved in ethanol-induced desensitization of adenosine receptor function. Therefore, we have examine the acute and chronic effects of ethanol on the transport of adenosine via the nucleoside transport. Acute exposure to ethanol caused an inhibition of adenosine uptake in S49 lymphoma cells. This decrease in uptake resulted in accumulation of extracellular adenosine after ethanol exposure. The effect of ethanol was specific to nucleoside transport. Uptake of uridine, also transported by the nucleoside transporter, was inhibited by ethanol to the same degree as adenosine uptake, while neither isoleucine nor deoxyglucose uptake was altered by ethanol treatment. Inhibition of adenosine uptake by ethanol was non-competitive and dependent on the concentration of ethanol. After chronic exposure to ethanol, cells became tolerant to the acute effects of ethanol. There was no longer an acute inhibition of adenosine uptake, nor was these accumulation of extracellular adenosine. Chronic ethanol exposure also resulted in a decrease in the absolute rate of adenosine uptake. Binding studies using a high affinity lignad for the nucleoside transporter, nitrobenzylthioinosine (NBMPR), indicate that this decreased uptake was due to a decrease in the maximal number of binding sites. These ethanol-induced changes in adenosine transport may be important for the acute and chronic effects of ethanol.

  3. The regulation of rat activity following exposure to hyperdynamic fields

    NASA Technical Reports Server (NTRS)

    Fuller, Charles A.; Ishihama, Linda M.; Murakami, Dean M.

    1993-01-01

    The microgravity of space flight and the hyperdynamic fields produced via centrifugation have allowed researchers to examine the effect of altered gravitational environments on the regulation of physiological systems. In this study, a high frequency light/dark cycle was provided for 24 hours as an environmental challenge to assess the recovery of homeostatic and circadian components of physiological regulation in rats. For example, the nocturnal rat exhibited a homeostatic increase in body temperature during the dark periods and a decrease during the light periods. In addition, the magnitude of the body temperature response exhibits a time of day variation demonstrating the effect on circadian regulation.

  4. Prenatal cocaine exposure impairs cognitive function of progeny via insulin growth factor II epigenetic regulation.

    PubMed

    Zhao, Qian; Hou, Jing; Chen, Bo; Shao, Xue; Zhu, Ruiming; Bu, Qian; Gu, Hui; Li, Yan; Zhang, Baolai; Du, Changman; Fu, Dengqi; Kong, Jueying; Luo, Li; Long, Hailei; Li, Hongyu; Deng, Yi; Zhao, Yinglan; Cen, Xiaobo

    2015-10-01

    Studies have showed that prenatal cocaine exposure (PCOC) can impair cognitive function and social behavior of the offspring; however, the mechanism underlying such effect is poorly understood. Insulin-like growth factor II (Igf-II), an imprinted gene, has a critical role in memory consolidation and enhancement. We hypothesized that epigenetic regulation of hippocampal Igf-II may attribute to the cognitive deficits of PCOC offspring. We used Morris water maze and open-field task to test the cognitive function in PCOC offspring. The epigenetic alteration involved in hippocampal Igf-II expression deficit in PCOC offspring was studied by determining Igf-II methylation status, DNA methyltransferases (DNMT) expressions and L-methionine level. Moreover, IGF-II rescue experiments were performed and the downstream signalings were investigated in PCOC offspring. In behavioral tests, we observed impaired spatial learning and memory and increased anxiety in PCOC offspring; moreover, hippocampal IGF-II mRNA and protein expressions were significantly decreased. Hippocampal methylation of cytosine-phospho-guanine (CpG) dinucleotides in differentially methylated region (DMR) 2 of Igf-II was elevated in PCOC offspring, which may be driven by the upregulation of L-methionine and DNA methyltransferase (DNMT) 1. Importantly, intra-hippocampal injection of recombinant IGF-II reactivated the repressed calcium calmodulin kinase II α (CaMKIIα) and reversed cognitive deficits in PCOC offspring. Collectively, our findings suggest that cocaine exposure during pregnancy impairs cognitive function of offspring through epigenetic modification of Igf-II gene. Enhancing IGF-II signaling may represent a novel therapeutical strategy for cocaine-induced cognitive impairment.

  5. Long non-coding RNA CCAT2 is up-regulated in gastric cancer and associated with poor prognosis

    PubMed Central

    Wang, Chen-Yu; Hua, Long; Yao, Kun-Hou; Chen, Jiang-Tao; Zhang, Jun-Jie; Hu, Jun-Hong

    2015-01-01

    Introduction: Dysregulation of long non-coding RNAs (lncRNAs) play important roles in tumor progression. The aim of our study was to explore the clinicopathologic and prognostic significance of lncRNA CCAT2 expression in human gastric cancer. Methods: Expression levels of lncRNA CCAT2 in 85 pairs of gastric cancer and adjacent non-tumor tissues were detected by quantitative real-time PCR (qRT-PCR). In order to determine its prognostic value, overall survival and progression-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: Expression levels of lncRNA CCAT2 in gastric cancer tissues were significantly higher than those in adjacent non-tumor tissues. By statistical analyses, high lncRNA CCAT2 expression was observed to be closely correlated with higher incidence of lymph node metastasis and distance metastasis. Moreover, patients with high lncRNA CCAT2 expression had shorter overall survival and progression-free survival compared with the low lncRNA CCAT2 group. Multivariate analyses indicated that high lncRNA CCAT2 expression was an independent poor prognostic factor for gastric cancer patients. Conclusions: Our results suggested that up-regulation of lncRNA CCAT2 was correlated with gastric cancer progression, and lncRNA CCAT2 might be a potential molecular biomarker for predicting the prognosis of patients. PMID:25755774

  6. 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

  7. NCAPG2 promotes tumour proliferation by regulating G2/M phase and associates with poor prognosis in lung adenocarcinoma.

    PubMed

    Zhan, Ping; Xi, Guang-Min; Zhang, Bin; Wu, Ying; Liu, Hong-Bing; Liu, Ya-Fang; Xu, Wu-Jian; Zhu, Qingqing; Cai, Feng; Zhou, Ze-Jun; Miu, Ying-Ying; Wang, Xiao-Xia; Jin, Jia-Jia; Li, Qian; Lv, Tang-Feng; Song, Yong

    2017-04-01

    NCAPG2 is a component of the condensin II complex and contributes to chromosome segregation via microtubule-kinetochore attachment during mitosis. It is well known that NCAPG2 plays a critical role in cell mitosis; however, the role of altered NCAPG2 expression and its transcriptional regulatory function in cancer development remains mostly unknown. Here, for the first time we reported that NCAPG2 was evidently increased in non-small cell lung cancer tissues compared to adjacent normal lung tissues. Clinicopathological data analysis showed that NCAPG2 overexpression was significantly correlated with lymph node metastasis and pathologic-Tumour Nodes Metastasen stages, and was an independent prognostic factor in lung adenocarcinoma patients. Moreover, siRNA-mediated knockdown of NCAPG2 could inhibit tumour cell growth of lung adenocarcinoma cells (A549 and H1299) in vitro and could significantly lead to cell cycle arrest in the G2 phase. Furthermore, we found that NCAPG2 silencing significantly decreased the expression levels of G2/M phase cell cycle-related protein expressions (Cyclin B1, Cdc2) and increased the expression levels of p27 and p21 through Western blot analysis. Taken together, we demonstrated that increased NCAPG2 expression could regulate cell proliferation and identified as a poor prognostic biomarker in lung adenocarcinoma.

  8. 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.

  9. Impact of a modification of food regulation on cadmium exposure.

    PubMed

    Jean, Julien; Sirot, Véronique; Vasseur, Paule; Narbonne, Jean-François; Leblanc, Jean-Charles; Volatier, Jean-Luc; Rivière, Gilles

    2015-10-01

    The 2nd French Total Diet Study demonstrated that 0.6% of adults and 14.9% of children exceeded the tolerable weekly intake set by EFSA. The overexposure of several consumers (adults and children) can be partially due to the high consumption of bread and dried bread products, of bivalve mollusks and of potatoes. Except for mollusks, these foods are the main contributors identified for the general population. On this basis, the French agency for food, environmental and occupational health and safety (ANSES) assessed whether a decrease of the European maximum limits in foodstuffs could significantly reduce the level of exposure of French consumers. Applying ML set at P90 of the main contributors would neither significantly reduce exposure levels to cadmium for the general population, nor the percentage of subjects exceeding the TWI. To reduce background consumer exposure to cadmium, actions to be taken include efforts on sources that are at the origin of the soil contamination and the efficacy of consumption recommendations.

  10. 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.

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

    PubMed

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

    2015-03-13

    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.

  12. 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

  13. 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.

  14. UHRF1 regulates global DNA hypomethylation and is associated with poor prognosis in esophageal squamous cell carcinoma

    PubMed Central

    Nakamura, Kenichi; Baba, Yoshifumi; Kosumi, Keisuke; Harada, Kazuto; Shigaki, Hironobu; Miyake, Keisuke; Kiyozumi, Yuki; Ohuchi, Mayuko; Kurashige, Junji; Ishimoto, Takatsugu; Iwatsuki, Masaaki; Sakamoto, Yasuo; Yoshida, Naoya; Watanabe, Masayuki; Nakao, Mitsuyoshi; Baba, Hideo

    2016-01-01

    Background Global DNA hypomethylation contributes to oncogenesis through various mechanisms. The level of long interspersed nucleotide element-1 (LINE- 1) methylation is considered a surrogate marker of global DNA methylation, and is attracting interest as a good predictor of cancer prognosis. However, the mechanism how LINE-1 (global DNA) methylation is controlled in cancer cells remains to be fully elucidated. Ubiquitin-like with PHD and RING finger domain 1 (UHRF1) plays a crucial role in DNA methylation. UHRF1 is overexpressed in many cancers, and UHRF1 overexpression may be a mechanism underlying DNA hypomethylation in cancer cells. Nonetheless, the relationship between UHRF1, LINE-1 methylation level, and clinical outcome in esophageal squamous cell carcinoma (ESCC) remains unclear. Results In ESCC cell lines, vector-mediated UHRF1 overexpression caused global DNA (LINE-1) hypomethylation and, conversely, UHRF1 knockdown using siRNA increased the global DNA methylation level. In ESCC tissues, UHRF1 expression was significantly associated with LINE-1 methylation levels. Furthermore, UHRF1 overexpression correlated with poor prognosis in our cohort of 160 ESCC patients. Materials and Methods The relationships between UHRF1 expression and LINE-1 methylation level (i.e., global DNA methylation level) were investigated using ESCC tissues and cell lines. In addition, we examined the correlation between UHRF1 expression, LINE-1 methylation, and clinical outcome in patients with ESCC. Conclusions Our results suggest that UHRF1 is a key epigenetic regulator of DNA methylation and might be a potential target for cancer treatment. PMID:27507047

  15. 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

  16. Bioenergetic adaptation in response to autophagy regulators during rotenone exposure

    PubMed Central

    Giordano, Samantha; Dodson, Matthew; Ravi, Saranya; Redmann, Matthew; Ouyang, Xiaosen; Usmar, Victor M Darley; Zhang, Jianhua

    2015-01-01

    Parkinson’s disease (PD) is the second most common neurodegenerative disorder with both mitochondrial dysfunction and insufficient autophagy playing a key role in its pathogenesis. Among the risk factors, exposure to the environmental neurotoxin rotenone increases the probability of developing PD. We previously reported that in differentiated SH-SY5Y cells, rotenone-induced cell death is directly related to inhibition of mitochondrial function. How rotenone at nM concentrations inhibits mitochondrial function, and whether it can engage the autophagy pathway necessary to remove damaged proteins and organelles, is unknown. We tested the hypothesis that autophagy plays a protective role against rotenone toxicity in primary neurons. We found that rotenone (10–100 nM) immediately inhibited cellular bioenergetics. Concentrations that decreased mitochondrial function at 2 hr, caused cell death at 24 hr with an LD50 of 10 nM. Overall autophagic flux was decreased by 10 nM rotenone at both 2 and 24 hr, but surprisingly mitophagy, or autophagy of the mitochondria, was increased at 24 hr, suggesting that a mitochondrial-specific lysosomal degradation pathway may be activated. Upregulation of autophagy by rapamycin protected against cell death while inhibition of autophagy by 3-methyladenine (3-MA) exacerbated cell death. Interestingly, while 3-MA exacerbated the rotenone-dependent effects on bioenergetics, rapamycin did not prevent rotenone-induced mitochondrial dysfunction, but caused reprogramming of mitochondrial substrate usage associated with both complex I and complex II activities. Taken together, these data demonstrate that autophagy can play a protective role in primary neuron survival in response to rotenone; moreover, surviving neurons exhibit bioenergetic adaptations to this metabolic stressor. PMID:25081478

  17. Prenatal tobacco exposure and self-regulation in early childhood: Implications for developmental psychopathology.

    PubMed

    Wiebe, Sandra A; Clark, Caron A C; De Jong, Desiree M; Chevalier, Nicolas; Espy, Kimberly Andrews; Wakschlag, Lauren

    2015-05-01

    Prenatal tobacco exposure (PTE) has a well-documented association with disruptive behavior in childhood, but the neurocognitive effects of exposure that underlie this link are not sufficiently understood. The present study was designed to address this gap, through longitudinal follow-up in early childhood of a prospectively enrolled cohort with well-characterized prenatal exposure. Three-year-old children (n = 151) were assessed using a developmentally sensitive battery capturing both cognitive and motivational aspects of self-regulation. PTE was related to motivational self-regulation, where children had to delay approach to attractive rewards, but not cognitive self-regulation, where children had to hold information in mind and inhibit prepotent motor responses. Furthermore, PTE predicted motivational self-regulation more strongly in boys than in girls, and when propensity scores were covaried to control for confounding risk factors, the effect of PTE on motivational self-regulation was significant only in boys. These findings suggest that PTE's impact on neurodevelopment may be greater in boys than in girls, perhaps reflecting vulnerability in neural circuits that subserve reward sensitivity and emotion regulation, and may also help to explain why PTE is more consistently related to disruptive behavior disorders than attention problems.

  18. 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…

  19. 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).…

  20. 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.

  1. Determining the Impact of Prenatal Tobacco Exposure on Self-regulation at Six Months

    PubMed Central

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

    2014-01-01

    The goal of 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

  2. 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.

  3. 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.

  4. 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.

  5. Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation

    PubMed Central

    Chang, Wei-Min; Lin, Yuan-Feng; Su, Chia-Yi; Peng, Hsuan-Yu; Chang, Yu-Chan; Hsiao, Jenn-Ren; Chen, Chi-Long; Chang, Jang-Yang; Shieh, Yi-Shing; Hsiao, Michael; Shiah, Shine-Gwo

    2017-01-01

    Parathyroid Hormone-Like Hormone (PTHLH) is an autocrine/paracrine ligand that is up-regulated in head and neck squamous cell carcinoma (HNSCC). However, the cellular function and regulatory mechanism in HNSCC remains obscure. We investigated the clinical significance of PTHLH in HNSCC patients, and verified the role of RUNX2/PTHLH axis, which is stimulated HNSCC cell growth. In patients, PTHLH is a poor prognosis marker. PTHLH expression lead to increasing the cell proliferation potential through an autocrine/paracrine role and elevating blood calcium level in Nod-SCID mice. In public HNSCC microarray cohorts, PTHLH is found to be co-expressed with RUNX2. Physiologically, PTHLH is regulated by RUNX2 and also acting as key calcium regulator. However, elevations of calcium concentration also increased the RUNX2 expression. PTHLH, calcium, and RUNX2 form a positive feedback loop in HNSCC. Furthermore, ectopic RUNX2 expression also increased PTHLH expression and promoted proliferation potential through PTHLH expression. Using cDNA microarray analysis, we found PTHLH also stimulated expression of cell cycle regulators, namely CCNA2, CCNE2, and CDC25A in HNSCC cells, and these genes are also up-regulated in HNSCC patients. In summary, our results reveal that PTHLH expression is a poor prognosis marker in HNSCC patients, and RUNX2-PTHLH axis contributes to HNSCC tumor growth. PMID:28120940

  6. Chronic exposure to fibrin and fibrinogen differentially regulates intracellular Ca2+ in human pulmonary arterial smooth muscle and endothelial cells.

    PubMed

    Firth, Amy L; Yau, Jocelyn; White, Amanda; Chiles, Peter G; Marsh, James J; Morris, Timothy A; Yuan, Jason X-J

    2009-06-01

    Acute pulmonary embolism occurs in more than half a million people a year in the United States. Chronic thromboembolic pulmonary hypertension (CTEPH) develops in approximately 4% of these patients due to unresolved thromboemboli. CTEPH is thus a relatively common, progressive, and potentially fatal disease. One currently proposed theory for the poor resolution advocates that modification of fibrinogen in CTEPH patients causes resistance of emboli to fibrinolysis. The current study investigated the regulation of cytosolic Ca(2+) ([Ca(2+)](cyt)), central to the control of cell migration, proliferation, and contraction, by chronic exposure of pulmonary artery smooth muscle (PASMC) and endothelial (PAEC) cells to fibrinogen and fibrin. Basal [Ca(2+)](cyt) was substantially elevated in PAEC after culture on fibrinogen, fibrin, and thrombin and in PASMC on fibrinogen and fibrin. In PAEC, fibrinogen significantly decreased the peak [Ca(2+)](cyt) transient (P <0.001) without a change in the transient peak width (at 50% of the peak height). This response was independent of effects on the proteinase-activated receptor (PAR) 1. Furthermore, chronic exposure to thrombin, an activator of PAR, significantly reduced the peak agonist-induced Ca(2+) release in PAEC, but increased it in PASMC. The recovery rate of the agonist-induced [Ca(2+)](cyt) transients decelerated in PASMC chronically exposed to fibrin; a small increase of the peak Ca(2+) was also observed. Substantial augmentation of PASMC (but not PAEC) proliferation was observed in response to chronic fibrin exposure. In conclusion, chronic exposure to fibrinogen, fibrin, and thrombin caused differential changes in [Ca(2+)](cyt) in PAEC and PASMC. Such changes in [Ca(2+)](cyt) may contribute to vascular changes in patients who have CTEPH where the pulmonary vasculature is persistently exposed to thromboemboli.

  7. Chronic exposure to fibrin and fibrinogen differentially regulates intracellular Ca2+ in human pulmonary arterial smooth muscle and endothelial cells

    PubMed Central

    Firth, Amy L.; Yau, Jocelyn; White, Amanda; Chiles, Peter G.; Marsh, James J.; Morris, Timothy A.; Yuan, Jason X.-J.

    2009-01-01

    Acute pulmonary embolism occurs in more than half a million people a year in the United States. Chronic thromboembolic pulmonary hypertension (CTEPH) develops in ∼4% of these patients due to unresolved thromboemboli. CTEPH is thus a relatively common, progressive, and potentially fatal disease. One currently proposed theory for the poor resolution advocates that modification of fibrinogen in CTEPH patients causes resistance of emboli to fibrinolysis. The current study investigated the regulation of cytosolic Ca2+ ([Ca2+]cyt), central to the control of cell migration, proliferation, and contraction, by chronic exposure of pulmonary artery smooth muscle (PASMC) and endothelial (PAEC) cells to fibrinogen and fibrin. Basal [Ca2+]cyt was substantially elevated in PAEC after culture on fibrinogen, fibrin, and thrombin and in PASMC on fibrinogen and fibrin. In PAEC, fibrinogen significantly decreased the peak [Ca2+]cyt transient (P <0.001) without a change in the transient peak width (at 50% of the peak height). This response was independent of effects on the proteinase-activated receptor (PAR) 1. Furthermore, chronic exposure to thrombin, an activator of PAR, significantly reduced the peak agonist-induced Ca2+ release in PAEC, but increased it in PASMC. The recovery rate of the agonist-induced [Ca2+]cyt transients decelerated in PASMC chronically exposed to fibrin; a small increase of the peak Ca2+ was also observed. Substantial augmentation of PASMC (but not PAEC) proliferation was observed in response to chronic fibrin exposure. In conclusion, chronic exposure to fibrinogen, fibrin, and thrombin caused differential changes in [Ca2+]cyt in PAEC and PASMC. Such changes in [Ca2+]cyt may contribute to vascular changes in patients who have CTEPH where the pulmonary vasculature is persistently exposed to thromboemboli. PMID:19363122

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

    PubMed

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

  9. Local Adaptation of Sun-Exposure-Dependent Gene Expression Regulation in Human Skin

    PubMed Central

    Kita, Ryosuke; Fraser, Hunter B.

    2016-01-01

    Sun-exposure is a key environmental variable in the study of human evolution. Several skin-pigmentation genes serve as classical examples of positive selection, suggesting that sun-exposure has significantly shaped worldwide genomic variation. Here we investigate the interaction between genetic variation and sun-exposure, and how this impacts gene expression regulation. Using RNA-Seq data from 607 human skin samples, we identified thousands of transcripts that are differentially expressed between sun-exposed skin and non-sun-exposed skin. We then tested whether genetic variants may influence each individual’s gene expression response to sun-exposure. Our analysis revealed 10 sun-exposure-dependent gene expression quantitative trait loci (se-eQTLs), including genes involved in skin pigmentation (SLC45A2) and epidermal differentiation (RASSF9). The allele frequencies of the RASSF9 se-eQTL across diverse populations correlate with the magnitude of solar radiation experienced by these populations, suggesting local adaptation to varying levels of sunlight. These results provide the first examples of sun-exposure-dependent regulatory variation and suggest that this variation has contributed to recent human adaptation. PMID:27760139

  10. Co-regulation of movement speed and accuracy by children with heavy prenatal alcohol exposure.

    PubMed

    Simmons, Roger W; Madra, Naju J; Levy, Susan S; Riley, Edward P; Mattson, Sarah N

    2011-02-01

    The study investigated how children with heavy prenatal alcohol exposure regulate movement speed and accuracy during goal-directed movements. 16 children ages 7 to 17 years with confirmed histories of heavy in utero alcohol exposure, and 21 nonalcohol-exposed control children completed a series of reciprocal tapping movements between two spatial targets. 5 different targets sets were presented, representing a range of task difficulty between 2 and 6 bits of information. Estimates of percent error rate, movement time, slope, and linear fit of the resulting curve confirmed that for goal-directed, reciprocal tapping responses, performance of the group with prenatal alcohol exposure was described by a linear function, as predicted by Fitts' law, by sacrificing movement accuracy. The index of performance was the same for the two groups: it initially increased, then leveled off for more difficult movements.

  11. Quantitative assessment of lives lost due to delay in the regulation of occupational exposure to benzene

    SciTech Connect

    Nicholson, W.J.; Landrigan, P.J. )

    1989-07-01

    Benzene exposure can cause leukemia, aplastic anemia, and possibly lymphoma. In 1978, on the basis of strong but incomplete data then available on the risk of benzene-induced leukemia, the U.S. Occupational Safety and Health Administration (OSHA) reduced the permissible occupational exposure standard for benzene from 10 ppm to 1 ppm. Shortly thereafter, the Fifth Circuit Court of Appeals stayed this ruling, and in 1980, the Supreme Court overturned the regulation, citing insufficient evidence of benefit. Thus, from 1978 until the standard was again lowered to 1 ppm in 1987, American workers were exposed to benzene at levels in excess of 1 ppm. An estimated 9600 were exposed to levels between 1 and 10 ppm, and an additional 370 were exposed at levels above 10 ppm. To assess the risk resulting from this delay in regulation, we have conducted an epidemiologic risk analysis. We merged data on numbers of persons (238,000) exposed to benzene in seven occupational categories with dose-response data from three epidemiologic studies. The range of risk in these studies indicates that 44 to 152 excess leukemia deaths will ultimately result from exposure to benzene at 10 ppm over a working lifetime (45 years) and that lower or briefer exposures will result in proportionately fewer deaths. On this basis, we calculated that between 30 and 490 excess leukemia deaths will ultimately result from occupational exposures to benzene greater than 1 ppm that occurred between 1978 and 1987. Deaths from aplastic anemia and lymphoma will likely add to this toll. These data confirm the risk of regulatory delay. They suggest that the courts, in reviewing public health regulations, must beware of facile cost-benefit arguments and be willing to accept strong evidence of health risk even when such evidence is incomplete.

  12. CD44v6 down-regulation is an independent prognostic factor for poor outcome of colorectal carcinoma.

    PubMed

    Wang, Lili; Liu, Qin; Lin, Dongliang; Lai, Maode

    2015-01-01

    We aim to investigate the variation of CD44v6 expression in the normal-adenoma-primary carcinoma-liver metastasis sequence and its prognostic impact on colorectal carcinomas. The difference in CD44v6 expression between the tumor center and invasive front was also assessed. Immunohistochemistry was performed for CD44v6 on two cohorts. The first was tissue microarrays including 402 primary CRCs sampled from the tumor center and the invasive margin. The second was whole-tissue sections, consisting of 217 adenomas, 72 primary carcinomas, and the corresponding metastatic carcinomas. In the first cohort, we found that CD44v6 down-regulation was inclined to lymph node metastasis and perineural invasion, and had an unfavorable prognosis compared with CD44v6 up-regulation. In the second cohort, CD44v6 expression was predominant in adenoma over primary carcinoma and liver metastasis in multiple steps (normal < adenoma > primary carcinoma and liver metastasis). In addition, our analysis showed that CD44v6 expression was decreased at the invasion front of the CRC compared with the center of the tumor. In conclusion, the maximal expression of CD44v6 in adenoma plays a crucial role in colorectal carcinogenesis, while loss of CD44v6 expression on the cell surface of the tumor edge enhances the progression of metastasis. CD44v6 down-regulation is an independent prognostic factor for strikingly worse disease-specific survival.

  13. Epigenetic Regulation: The Interface Between Prenatal and Early-Life Exposure and Asthma Susceptibility

    PubMed Central

    de Planell-Saguer, Mariangels; Lovinsky-Desir, Stephanie; Miller, Rachel L.

    2014-01-01

    Asthma is a complex disease with genetic and environmental influences and emerging evidence suggests that epigenetic regulation is also a major contributor. Here, we focus on the developing paradigm that epigenetic dysregulation in asthma and allergy may start as early as in utero following several environmental exposures. We summarize the pathways important to the allergic immune response that are epigenetically regulated, the key environmental exposures associated with epigenetic changes in asthma genes, and newly identified epigenetic bio-markers that have been linked to clinical asthma. We conclude with a brief discussion about the potential to apply newly developing technologies in epigenetics to the diagnosis and treatment of asthma and allergy. The inherent plasticity of epigenetic regulation following environmental exposures offers opportunities for prevention using environmental remediation, measuring novel biomarkers for early identification of those at risk, and applying advances in pharmaco-epigenetics to tailor medical therapies that maximize efficacy of treatment. ‘Precision Medicine’ in asthma and allergy is arriving. As the field advances this may involve an individually tailored approach to the prevention, early detection, and treatment of disease based on the knowledge of an individual’s epigenetic profile. PMID:24323745

  14. A collagen-remodeling gene signature regulated by TGFβ signaling is associated with metastasis and poor survival in serous ovarian cancer

    PubMed Central

    Cheon, Dong-Joo; Tong, Yunguang; Sim, Myung-Shin; Dering, Judy; Berel, Dror; Cui, Xiaojiang; Lester, Jenny; Beach, Jessica A.; Tighiouart, Mourad; Walts, Ann E.; Karlan, Beth Y.; Orsulic, Sandra

    2013-01-01

    Purpose To elucidate molecular pathways contributing to metastatic cancer progression and poor clinical outcome in serous ovarian cancer. Experimental Design Poor survival signatures from three different serous ovarian cancer datasets were compared and a common set of genes was identified. The predictive value of this gene signature was validated in independent datasets. The expression of the signature genes was evaluated in primary, metastatic, and/or recurrent cancers using qPCR and in situ hybridization. Alterations in gene expression by TGFβ1 and functional consequences of loss of COL11A1 were evaluated using pharmacologic and knockdown approaches, respectively. Results We identified and validated a 10-gene signature (AEBP1, COL11A1, COL5A1, COL6A2, LOX, POSTN, SNAI2, THBS2, TIMP3, VCAN) that is associated with poor overall survival in patients with high-grade serous ovarian cancer. The signature genes encode extracellular matrix proteins involved in collagen remodeling. Expression of the signature genes is regulated by TGFβ1 signaling and is enriched in metastases in comparison to primary ovarian tumors. We demonstrate that levels of COL11A1, one of the signature genes, continuously increase during ovarian cancer disease progression, with the highest expression in recurrent metastases. Knockdown of COL11A1 decreases in vitro cell migration and invasion and tumor progression in mice. Conclusion Our findings suggest that collagen-remodeling genes regulated by TGFβ1 signaling promote metastasis and contribute to poor overall survival in patients with serous ovarian cancer. Our 10-gene signature has both predictive value and biological relevance and thus may be useful as a therapeutic target. PMID:24218511

  15. 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

    2015-10-02

    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.

  16. 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.

  17. Long non-coding RNA BANCR regulates growth and metastasis and is associated with poor prognosis in retinoblastoma.

    PubMed

    Su, Shizheng; Gao, Jian; Wang, Tao; Wang, Ju; Li, Hong; Wang, Zhen

    2015-09-01

    Recent evidence shows that BRAF-activated non-coding RNA (BANCR) acts as a critical role in the proliferation and metastasis in malignant melanoma and lung cancer; however, little is known about the significance of lncRNA BANCR in retinoblastoma. The purpose of our study is to explore the role of lncRNA BANCR in retinoblastoma clinical samples and cell lines. The expression of lncRNA BANCR was measured in 60 retinoblastoma samples and normal retina samples by using RT-PCR. The effects of lncRNA BANCR on cell proliferation, migration, and invasion were also explored. In our results, lncRNA BANCR is overexpressed in retinoblastoma tissues and cell lines and is associated with tumor size, choroidal invasion, and optic nerve invasion. Moreover, patients with high levels of lncRNA BANCR expression had poorer survival than those with lower levels of lncRNA BANCR expression. Multivariate analysis showed that increased lncRNA BANCR expression was a poor independent prognostic factor for retinoblastoma patients. Furthermore, knocking down lncRNA BANCR expression significantly suppressed the retinoblastoma cell proliferation, migration, and invasion in vitro. In conclusion, lncRNA BANCR plays a significant role in retinoblastoma aggressiveness and prognosis and may act as a promising target for therapeutic strategy and prognostic prediction.

  18. Exposure to Fluorescent Light Triggers Down Regulation of Genes Involved with Mitotic Progression in Xiphophorus Skin

    PubMed Central

    Walter, Ronald B.; Walter, Dylan J.; Boswell, William T.; Caballero, Kaela L.; Boswell, Mikki; Lu, Yuan; Chang, Jordan; Savage, Markita G.

    2015-01-01

    We report RNA-Seq results from skin of X. maculatus Jp 163 B after exposure to various doses of “cool white” fluorescent light (FL). We show that FL exposure incites a genetic transcriptional response in skin nearly as great as observed for UVB exposure; however, the gene sets modulated due to exposure to the two light sources are quite different. Known light responsive genes involved in maintaining circadian cycling (e.g., clock, cry2a, cry1b, per1b, per2, per3, arntl1a, etc.) exhibited expected shifts in transcriptional expression upon FL exposure. Exposure to FL also resulted in down-regulated transcription of many genes involved with cell cycle progression (e.g., cdc20, cdc45, cdca7b, plk1, cdk1, ccnb-3, cdca7a, etc.) and chromosome segregation (e.g., cenpe, cenpf, cenpi, cenpk, cenpo, cenpp, and cenpu; cep70; knstrm, kntc, mcm2, mcm5; smc2, etc.). In addition, several DNA replication and recombination repair genes (e.g., pola1, pole, rec52, rad54l, rpa1, parpbp, etc.) exhibit reduced expression in FL exposed X. maculatus skin. Some genes down modulated by FL are known to be associated with DNA repair and human diseases (e.g., atm2, brip1, fanc1, fancl, xrcc4, etc.). The overall suppression of genes involved with mitotic progression in the skin of adult fish is consistent with entry into the light phase of the circadian cycle. Current efforts are aimed at determining specific wavelengths that may lead to differential expression among the many genes affected by fluorescent light exposure. PMID:26334372

  19. 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

  20. 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

  1. Downregulated ECRG4 is associated with poor prognosis in renal cell cancer and is regulated by promoter DNA methylation.

    PubMed

    Luo, Liya; Wu, Jianting; Xie, Jun; Xia, Lingling; Qian, Xuemin; Cai, Zhiming; Li, Zesong

    2016-01-01

    Esophageal cancer-related gene 4 (ECRG4) has been proposed as a putative tumor suppressor gene in several tumors. However, the role and regulation of ECRG4 in the pathogenesis of human renal cancer remain largely unknown. Our current study revealed that expression of ECRG4 is downregulated in renal cell lines and renal cancer tissues. ECRG4 expression was significantly associated with histological grade of tumors (p < 0.001), primary tumor stage (p = 0.017), and distant metastasis (p = 0.017). Low expression of ECRG4 was an independent prognostic indicator for survival of renal cancer patients. Silencing of ECRG4 expression in renal cell lines was associated with its promoter methylation. Moreover, ectopic expression of ECRG4 markedly inhibited cell proliferation and invasion in renal cancer cell lines. These results indicated that ECRG4 is frequently silenced by the methylation of promoter in renal cell cancers. ECRG4 may be a tumor suppressor in renal cancer and serve as a prognostic marker.

  2. Abnormal regulation for progesterone production in placenta with prenatal cocaine exposure in rats.

    PubMed

    Wu, L; Yan, J; Qu, S C; Feng, Y Q; Jiang, X L

    2012-12-01

    Cocaine abuse in pregnant women is currently a significant public hygiene problem and is tightly associated with elevated risk for preterm delivery. Placental steroidogenesis especially progesterone production was essential for success and maintenance of pregnancy in humans and rodents. In the present study, we determined the impact of prenatal cocaine exposure on pathways of placental progesterone synthesis in rats. Pregnant rats were treated cocaine twice daily (15 mg/kg/day) during the third trimester, and the maternal and fetal plasma progesterone and pregnenolone concentrations were detected. We also examined both the protein and mRNA expression of some key enzymes and regulators for progesterone production in placenta. Results showed that, after maternal cocaine use during pregnancy, progesterone and pregnenolone concentrations in both maternal and fetal rats were significantly decreased. Although prenatal cocaine exposure had no effects on placental 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) expression, protein and mRNA expression of the cholesterol side-chain cleavage enzyme (P450scc/CYP11a) in placenta was significantly inhibited. Moreover, protein and mRNA expressions of MLN64 that regulating cholesterol transport and activating protein 2γ (AP2γ/Tfap2c) that controlling P450scc/CYP11a gene expression in placenta were both decreased following maternal cocaine use in pregnancy. Collectively, this study suggested that prenatal cocaine exposure could insult the placental progesterone production in rats possibly associated with the high risk for preterm delivery.

  3. 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.

  4. 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.

  5. Long non-coding RNA CCAT2 is associated with poor prognosis in hepatocellular carcinoma and promotes tumor metastasis by regulating Snail2-mediated epithelial–mesenchymal transition

    PubMed Central

    Xu, Yongfu; Wang, Binfeng; Zhang, Fabiao; Wang, Aidong; Du, Xuefeng; Hu, Peng; Zhu, Yu; Fang, Zheping

    2017-01-01

    Increasing evidence has demonstrated that aberrant expressions of long non-coding RNAs (lncRNAs) are involved in various malignancies, including hepatocellular carcinoma (HCC). This study aimed to investigate the role of lncRNA colon cancer-associated transcript 2 (CCAT2) in the progression of HCC. Quantitative real-time polymerase chain reaction analysis confirmed that CCAT2 was upregulated in HCC cell lines and cancerous tissues compared with normal liver cell line and adjacent normal tissue samples. The level of CCAT2 was positively associated with tumor–node–metastasis stages and vessel invasion. Survival analyses revealed that high CCAT2 expression predicted poor prognostic outcomes, serving as an independent prognostic factor for HCC patients. Patients with high CCAT2 expression had a 1.849-fold increased risk of death compared with those with low CCAT2 expression. Moreover, we also found that knockdown of CCAT2 expression reduced cell migration and invasion in vitro. We further demonstrated that CCAT2 played a key role in enhancing the epithelial–mesenchymal transition (EMT) through the regulation of vimentin, E-cadherin and transcription factor snail2 expression. Taken together, our findings showed that high CCAT2 expression is associated with poor survival in HCC patients. CCAT2 promotes HCC progression by regulating Snail2-induced EMT. CCAT2 may be a prognostic biomarker and therapeutic target for HCC. PMID:28280353

  6. High expression of long noncoding RNA HULC is a poor predictor of prognosis and regulates cell proliferation in glioma

    PubMed Central

    Yan, Hong; Tian, Rui; Zhang, Min; Wu, Jing; Ding, Min; He, Jie

    2017-01-01

    Purpose Emerging studies show that long noncoding RNAs (lncRNAs) have important roles in carcinogenesis. This study investigated the role of lncRNA highly upregulated in liver cancer (HULC) expression in glioma and its clinical significance in glioma patients. Materials and methods HULC expression was detected in glioma tissues and cell lines by using real-time quantitative reverse transcription polymerase chain reactions. Association between HULC levels and clinicopathological factors and patients prognosis was also analyzed. Expression of HULC was restored and knocked down in glioma cell line U87 by using HULC cDNA and siRNA, respectively. CCK-8 and colony formation assays were used to investigate the role of HULC in the regulation of proliferation of glioma cells. Results HULC was highly expressed in glioma tissues, being closely related to age and grade of glioma. Univariate survival analysis demonstrated that high HULC levels were significantly associated with overall survival (OS) (hazard ratio [HR], 0.422; 95% confidence interval [CI], 0.220–0.806; P=0.009), and it remained an independent predictor for OS (HR, 0.340; 95% CI, 0.175–0.659; P=0.001) in multivariate Cox regression analysis. Functionally, forced expression of HULC results in increased cell proliferation and colony formation of U87 glioma cell line, whereas knockdown of HULC expression reduced these oncogenic properties of glioma cells. Conclusion These findings suggest that HULC may play an important role in glioma progression and will be further evaluated as a biomarker for predicting the survival of glioma patients. PMID:28053545

  7. 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.

  8. Down-regulation of the rat serotonin transporter upon exposure to a selective serotonin reuptake inhibitor.

    PubMed

    Horschitz, S; Hummerich, R; Schloss, P

    2001-07-20

    The serotonin transporter (SERT) terminates serotonergic neurotransmission by rapid reuptake of 5-hydroxytryptamine (5-HT) into the nerve terminal or axonal varicosities. SERT represents the target of various antidepressants which inhibit 5-HT transport and are widely used for the pharmacotherapy of depression. Here, we have analyzed the function of SERT stably expressed in HEK 293 cells upon exposure to citalopram, a selective serotonin reuptake inhibitor (SSRI), with respect to 5-HT transport activity and protein expression as estimated by ligand binding experiments. Our results show that long-term exposure to an SSRI causes a down-regulation of transport activity as revealed by a reduction of the maximal transport rate, without affecting substrate affinity, accompanied by a decrease in ligand binding sites.

  9. 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.

  10. The Use of In Vitro Data and Physiologically-Based Pharmacokinetic Modeling to Predict Drug Metabolite Exposure: Desipramine Exposure in Cytochrome P4502D6 Extensive and Poor Metabolizers Following Administration of Imipramine.

    PubMed

    Nguyen, Hoa Q; Callegari, Ernesto; Obach, R Scott

    2016-10-01

    Major circulating drug metabolites can be as important as the drugs themselves in efficacy and safety, so establishing methods whereby exposure to major metabolites following administration of parent drug can be predicted is important. In this study, imipramine, a tricyclic antidepressant, and its major metabolite desipramine were selected as a model system to develop metabolite prediction methods. Imipramine undergoes N-demethylation to form the active metabolite desipramine, and both imipramine and desipramine are converted to hydroxylated metabolites by the polymorphic enzyme CYP2D6. The objective of the present study is to determine whether the human pharmacokinetics of desipramine following dosing of imipramine can be predicted using static and dynamic physiologically-based pharmacokinetic (PBPK) models from in vitro input data for CYP2D6 extensive metabolizer (EM) and poor metabolizer (PM) populations. The intrinsic metabolic clearances of parent drug and metabolite were estimated using human liver microsomes (CYP2D6 PM and EM) and hepatocytes. Passive diffusion clearance of desipramine, used in the estimation of availability of the metabolite, was predicted from passive permeability and hepatocyte surface area. The predicted area under the curve (AUCm/AUCp) of desipramine/imipramine was 12- to 20-fold higher in PM compared with EM subjects following i.v. or oral doses of imipramine using the static model. Moreover, the PBPK model was able to recover simultaneously plasma profiles of imipramine and desipramine in populations with different phenotypes of CYP2D6. This example suggested that mechanistic PBPK modeling combined with information obtained from in vitro studies can provide quantitative solutions to predict in vivo pharmacokinetics of drugs and major metabolites in a target human population.

  11. Overexpression of HnRNP A1 promotes tumor invasion through regulating CD44v6 and indicates poor prognosis for hepatocellular carcinoma.

    PubMed

    Zhou, Zheng-Jun; Dai, Zhi; Zhou, Shao-Lai; Fu, Xiu-Tao; Zhao, Yi-Ming; Shi, Ying-Hong; Zhou, Jian; Fan, Jia

    2013-03-01

    Heterogeneous ribonucleoprotein (hnRNP) A1 is a member of the A/B subfamily of ubiquitously expressed hnRNPs, which have a wide variety of functions in gene expression and signal transduction. To investigate the biological function and clinical significance of hnRNP A1 in hepatocellular carcinoma (HCC), we measured hnRNP A1 expression in four HCC cell lines and two independent cohorts of HCC patients. We found that hnRNP A1 was overexpressed in the highly metastatic HCC cell lines and in tumor tissues of patients with recurrent HCC. Knockdown of hnRNP A1 in highly metastatic HCC cells caused a significant decrease in cell invasion, while upregulation of hnRNP A1 in poorly metastatic HCC cells led to a significant increase in their invasive capacity. We found that this effect may occur through the regulation of CD44v6 expression by hnRNP A1 in HCC cells. Both quantitative reverse transcription-polymerase chain reaction (qRT-RCR) and immunohistochemistry revealed that hnRNP A1 was upregulated in HCC tissues and coincided with overexpression of CD44v6. HCC patients with high hnRNP A1 tended to have higher levels of CD44v6, shorter overall survival (OS) and higher rates of tumor recurrence. Multivariate analyses revealed that hnRNP A1 alone or in combination with CD44v6 were independent prognostic indicators for OS and time to recurrence and have potential as therapeutic targets. In conclusion, overexpression of hnRNP A1 promotes HCC invasion by regulating the level of CD44v6 and indicates a poor prognosis for HCC patients after curative resection.

  12. Vasopressin Regulation and Renal Fluid and Electrolyte Handling in Rat Models of Acute and Chronic alcohol Exposure

    DTIC Science & Technology

    2004-10-01

    evaluating fluid and electrolyte regulating ability in models of acute and chronic alcohol exposure and alcohol withdrawal, and 2) uncovering mechanisms ...be used to define mechanisms behind alcohol effects better than study of humans because conditions of alcohol dosing, hydration status, and fluid...vasopressin receptor regulation, and have determined that altered renal responsiveness to vasopressin is the main mechanism behind fluid balance perturbations

  13. Impaired regulation of divalent cations with acute copper exposure in the marine clam Mesodesma mactroides.

    PubMed

    Jorge, Marianna Basso; Lauer, Mariana Machado; Martins, Camila De Martinez Gaspar; Bianchini, Adalto

    2016-01-01

    The mechanism of copper (Cu) toxicity in marine invertebrates remains unclear. Therefore, marine clams (Mesodesma mactroides) were exposed (96h) to a concentration of dissolved Cu (1.6μmolL(-1)) inducing 10% mortality in sea water (30ppt). After in vivo exposure, tissue Cu accumulation (hemolymph, gill and digestive gland); hemolymph ionic (Na(+), K(+), Mg(2+) and Ca(2+)) and osmotic concentrations; tissue (gill and digestive gland) ionic concentration, enzyme (Na(+),K(+)-ATPase and carbonic anhydrase) activity, and oxygen consumption; and whole-body oxygen consumption were analyzed. Succinate dehydrogenase activity was evaluated in mitochondria isolated from gills and digestive gland and exposed (1h) in vitro to different concentrations of dissolved Cu (0.8, 7.7 and 78.7μmolL(-1)). In vivo exposure induced Cu accumulation in hemolymph, gills and digestive gland; increased Mg(2+) and decreased Ca(2+) concentration in hemolymph; decreased Mg(2+) concentration, increased Na(+),K(+)-ATPase activity and reduced carbonic anhydrase activity in gills; decreased Mg(2+) concentration, increased Ca(2+) concentration and increased Na(+),K(+)-ATPase activity in digestive gland; and reduced gill, digestive gland and whole-body oxygen consumption. Succinate dehydrogenase activity was inhibited after in vitro exposure to 78.7μmolL(-1) Cu. These findings indicate that Cu is an ionoregulatory toxicant in the marine clam M. mactroides. However, toxicity is related to disturbances in regulation of divalent cations (Mg(2+) and Ca(2+)) without effect on regulation of major monovalent cations (Na(+) and K(+)), as opposed to that observed in osmoregulating invertebrates exposed to Cu. However, other mechanism(s) of toxicity cannot be ruled out. Future studies must be performed to evaluate the consequence of the Cu-induced respiratory disturbances observed in M. mactroides.

  14. Regulation of Copper Transport Crossing Brain Barrier Systems by Cu-ATPases: Effect of Manganese Exposure

    PubMed Central

    Fu, Xue; Zhang, Yanshu; Jiang, Wendy; Monnot, Andrew Donald; Bates, Christopher Alexander; Zheng, Wei

    2014-01-01

    Regulation of cellular copper (Cu) homeostasis involves Cu-transporting ATPases (Cu-ATPases), i.e., ATP7A and ATP7B. The question as to how these Cu-ATPases in brain barrier systems transport Cu, i.e., toward brain parenchyma, cerebrospinal fluid (CSF), or blood, remained unanswered. This study was designed to characterize roles of Cu-ATPases in regulating Cu transport at the blood-brain barrier (BBB) and blood-CSF barrier (BCB) and to investigate how exposure to toxic manganese (Mn) altered the function of Cu-ATPases, thereby contributing to the etiology of Mn-induced parkinsonian disorder. Studies by quantitative real-time RT-PCR (qPCR), Western blot, and immunocytochemistry revealed that both Cu-ATPases expressed abundantly in BBB and BCB. Transport kinetic studies by in situ brain infusion and ventriculo-cisternal (VC) perfusion in Sprague Dawley rat suggested that the BBB was a major site for Cu entry into brain, whereas the BCB was a predominant route for Cu efflux from the CSF to blood. Confocal evidence showed that the presence of excess Cu or Mn in the choroid plexus cells led to ATP7A relocating toward the apical microvilli facing the CSF, but ATP7B toward the basolateral membrane facing blood. Mn exposure inhibited the production of both Cu-ATPases. Collectively, these data suggest that Cu is transported by the BBB from the blood to brain, which is mediated by ATP7A in brain capillary. By diffusion, Cu ions move from the interstitial fluid into the CSF, where they are taken up by the BCB. Within the choroidal epithelial cells, Cu ions are transported by ATP7B back to the blood. Mn exposure alters these processes, leading to Cu dyshomeostasis-associated neuronal injury. PMID:24614235

  15. Chronic lead exposure alters presynaptic calcium regulation and synaptic facilitation in Drosophila larvae.

    PubMed

    He, T; Hirsch, H V B; Ruden, D M; Lnenicka, G A

    2009-09-01

    Prolonged exposure to inorganic lead (Pb(2+)) during development has been shown to influence activity-dependent synaptic plasticity in the mammalian brain, possibly by altering the regulation of intracellular Ca(2+) concentration ([Ca(2+)](i)). To explore this possibility, we studied the effect of Pb(2+) exposure on [Ca(2+)](i) regulation and synaptic facilitation at the neuromuscular junction of larval Drosophila. Wild-type Drosophila (CS) were raised from egg stages through the third larval instar in media containing either 0 microM, 100 microM or 250 microM Pb(2+) and identified motor terminals were examined in late third-instar larvae. To compare resting [Ca(2+)](i) and the changes in [Ca(2+)](i) produced by impulse activity, the motor terminals were loaded with a Ca(2+) indicator, either Oregon Green 488 BAPTA-1 (OGB-1) or fura-2 conjugated to a dextran. We found that rearing in Pb(2+) did not significantly change the resting [Ca(2+)](i) nor the Ca(2+) transient produced in synaptic boutons by single action potentials (APs); however, the Ca(2+) transients produced by 10 Hz and 20 Hz AP trains were larger in Pb(2+)-exposed boutons and decayed more slowly. For larvae raised in 250 microM Pb(2+), the increase in [Ca(2+)](i) during an AP train (20 Hz) was 29% greater than in control larvae and the [Ca(2+)](i) decay tau was 69% greater. These differences appear to result from reduced activity of the plasma membrane Ca(2+) ATPase (PMCA), which extrudes Ca(2+) from these synaptic terminals. These findings are consistent with studies in mammals showing a Pb(2+)-dependent reduction in PMCA activity. We also observed a Pb(2+)-dependent enhancement of synaptic facilitation at these larval neuromuscular synapses. Facilitation of EPSP amplitude during AP trains (20 Hz) was 55% greater in Pb(2+)-reared larvae than in controls. These results showed that Pb(2+) exposure produced changes in the regulation of [Ca(2+)](i) during impulse activity, which could affect various

  16. Chronic lead exposure alters presynaptic calcium regulation and synaptic facilitation in Drosophila larvae

    PubMed Central

    He, T.; Hirsch, H.V.B.; Ruden, D. M.; Lnenicka, G. A.

    2009-01-01

    Prolonged exposure to inorganic lead (Pb2+) during development has been shown to influence activity-dependent synaptic plasticity in the mammalian brain, possibly by altering the regulation of intracellular Ca2+ concentration ([Ca2+]i). To explore this possibility, we studied the effect of Pb2+ exposure on [Ca2+]i regulation and synaptic facilitation at the neuromuscular junction of larval Drosophila. Wild-type Drosophila (CS) were raised from egg stages through the third larval instar in media containing either 0, 100 μM or 250 μM Pb2+ and identified motor terminals were examined in late third-instar larvae. To compare resting [Ca2+]i and the changes in [Ca2+]i produced by impulse activity, the motor terminals were loaded with a Ca2+ indicator, either Oregon Green 488 BAPTA-1 (OGB-1) or fura-2 conjugated to a dextran. We found that rearing in Pb2+ did not significantly change the resting [Ca2+]i nor the Ca2+ transient produced in synaptic boutons by single action potentials (APs); however, the Ca2+ transients produced by 10 and 20 Hz AP trains were larger in Pb2+-exposed boutons and decayed more slowly. For larvae raised in 250 μM Pb2+, the increase in [Ca2+]i during an AP train (20 Hz) was 29% greater than in control larvae and the [Ca2+]i decay τ was 69% greater. These differences appear to result from reduced activity of the plasma membrane Ca2+ ATPase (PMCA), which extrudes Ca2+ from these synaptic terminals. These findings are consistent with studies in mammals showing a Pb2+-dependent reduction in PMCA activity. We also observed a Pb2+-dependent enhancement of synaptic facilitation at these larval neuromuscular synapses. Facilitation of EPSP amplitude during AP trains (20 Hz) was 55% greater in Pb2+-reared larvae than in controls. These results showed that Pb2+ exposure produced changes in the regulation of [Ca2+]i during impulse activity, which could affect various aspects of nervous system development. At the mature synapse, this altered [Ca2+]i

  17. Exposure to caregiver maltreatment alters expression levels of epigenetic regulators in the medial prefrontal cortex

    PubMed Central

    Blaze, Jennifer; Roth, Tania L

    2013-01-01

    Quality of maternal care experienced during infancy is a key factor that can confer vulnerability or resilience to psychiatric disorders later in life. Research continues to indicate that early-life experiences can affect developmental trajectories through epigenetic alterations capable of affecting gene regulation and neural plasticity. Previously, our lab has shown that experiences within an adverse caregiving environment (i.e. maltreatment) produce aberrant DNA methylation patterns at various gene loci in the medial prefrontal cortex (mPFC) of developing and adult rats. This study aimed to determine whether caregiver maltreatment likewise affects expression levels of several genes important in regulating DNA methylation patterns (Dnmt1, Dnmt3a, MeCP2, Gadd45b, and Hdac1). While we observed minimal changes in gene expression within the mPFC of developing rats, we observed expression changes for all genes in adult animals. Specifically, exposure to maltreatment produced a significant decrease in mRNA levels of all epigenetic regulators in adult males and a significant decrease in Gadd45b in adult females. Our results here provide further empirical support for the long-term and sex-specific epigenetic consequences of caregiver maltreatment on the mPFC. PMID:24120634

  18. 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.

  19. 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

  20. Gallium arsenide selectively up-regulates inflammatory cytokine expression at exposure site.

    PubMed

    Becker, Stephen M; McCoy, Kathleen L

    2003-12-01

    Gallium arsenide (GaAs), a technologically and economically important semiconductor, is widely utilized in both military and commercial applications. This chemical is a potential health hazard as a carcinogen and immunotoxicant. We previously reported that macrophages at the exposure site exhibit characteristics of activation. In vitro culture of macrophages with GaAs fails to recapitulate the in vivo phenotype, suggesting that complete GaAs-mediated activation in vivo may require other cells or components found in the body's microenvironment. Our present study examined the role of cytokines upon GaAs-mediated macrophage activation. Intraperitoneal administration of GaAs elicited rapid specific recruitment of blood monocytes to the exposure site. This recruitment occurred concomitant with up-regulation of 17 chemokine and inflammatory cytokine mRNAs, while transcripts of three inhibitory cytokines diminished. Administration of latex beads caused less cytokine induction than GaAs, indicating that changes in mRNA levels could not be attributed to phagocytosis. Four representative chemokines and cytokines were selected for further analysis. Increased cytokine mRNA expression was paralleled by similar increases in cytokine protein levels, and secreted protein products were detected in peritoneal fluid. Cytokine protein expression was constrained to myeloid cells, and to a lesser extent to B cells. Alterations in patterns of cytokine gene expression elucidate mechanisms for increased cellular activation and antigen processing, and modulation of the inflammatory response. Our findings indicate that in vivo GaAs exposure alters cytokine gene expression, which may lead to an inflammatory reaction and contribute to pathological tissue damage.

  1. Regulation of Milk Intake After Exposure to Alcohol in Mothers’ Milk

    PubMed Central

    Mennella, Julie A.

    2009-01-01

    Objective Contrary to the folklore which claims that drinking alcohol during lactation benefits both mother and infant, previous research in our laboratory revealed that breastfed infants consumed significantly less milk during the immediate hours after their mothers’ consumption of an alcoholic beverage. Because breastfed infants are clearly capable of regulating milk intake, the present study tested the hypothesis that infants would compensate for the diminished milk intake if their mothers then refrained from drinking alcohol. Methods A within-subjects design that controlled for time of day was implemented because of the great individual and daily variation in both milk composition and intake. To this end, 12 exclusively breastfed infants and their mothers were tested on 2 days separated by 1 week. Each woman drank a 0.3 g/kg dose of alcohol in orange juice on one testing day and orange juice alone on the other; the order was counterbalanced. The infants’ behaviors were monitored for the next 16 hr, the first 4 hr of monitoring on each test day occurred at the Monell Center. The infants fed on demand and immediately before and after each feeding, infants were weighed without a change in clothing. Results Consistent with previous findings, infants consumed significantly less milk during the 4 hr immediately after exposure to alcohol in mothers’ milk compared with the control condition. Compensatory increases in intake were then observed during the 8 to 16 hr after exposure when mothers refrained from drinking alcohol. Conclusions These findings demonstrate that short-term exposure to small amounts of alcohol in mothers’ milk produces distinctive changes in the infants’ patterns of feeding. PMID:11329500

  2. Prenatal cocaine exposure alters emotional arousal regulation and its effects on working memory.

    PubMed

    Li, Zhihao; Coles, Claire D; Lynch, Mary Ellen; Hamann, Stephan; Peltier, Scott; LaConte, Stephen; Hu, Xiaoping

    2009-01-01

    While prenatal cocaine exposure (PCE) has been associated with arousal dysregulation and attentional impairments in both human and animal studies, the neurobiological bases of these teratogenic effects have not been well characterized. In the current study, we report functional neuroimaging observations of these effects in exposed youth. Using functional magnetic resonance imaging (fMRI), we embedded task-irrelevant emotional distracters in a working memory task to examine the interaction of emotional arousal and memory in 33 PCE and 23 non-exposed adolescents. Though with similar behavioral performance, the two groups exhibited different activation patterns associated with emotion-memory interactions. On the one hand, higher memory load attenuated emotion-related amygdala activation in controls but not in the exposed adolescents; on the other hand, prefrontal activation associated with memory load decreased in the presence of emotional distraction in the controls but increased in the exposed group. These group interaction differences suggest neurobiological substrates for arousal-associated neuronal alterations related to prenatal cocaine exposure. Consistent with previous findings in behavioral and physiological studies, the present neuroimaging data provided more in-depth evidence supporting the view that PCE has significant long-term teratogenic effect on arousal regulation system.

  3. Prenatal cocaine exposure alters emotional arousal regulation and its effects on working memory

    PubMed Central

    Li, Zhihao; Coles, Claire D.; Lynch, Mary Ellen; Hamann, Stephan; Peltier, Scott; LaConte, Stephen; Hu, Xiaoping

    2009-01-01

    While prenatal cocaine exposure (PCE) has been associated with arousal dysregulation and attentional impairments in both human and animal studies, the neurobiological bases of these teratogenic effects have not been well characterized. In the current study, we report functional neuroimaging observations of these effects in exposed youth. Using functional magnetic resonance imaging (fMRI), we embedded task-irrelevant emotional distracters in a working memory task to examine the interaction of emotional arousal and memory in 33 PCE and 23 non-exposed adolescents. Though with similar behavioral performance, the two groups exhibited different activation patterns associated with emotion-memory interactions. On the one hand, higher memory load attenuated emotion-related amygdala activation in controls but not in the exposed adolescents; on the other hand, prefrontal activation associated with memory load decreased in the presence of emotional distraction in the controls but increased in the exposed group. These group interaction differences suggest neurobiological substrates for arousal-associated neuronal alterations related to prenatal cocaine exposure. Consistent with previous findings in behavioral and physiological studies, the present neuroimaging data provided more in-depth evidence supporting the view that PCE has significant long-term teratogenic effect on arousal regulation system. PMID:19699795

  4. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation

    PubMed Central

    Rodgers, Ali B.; Morgan, Christopher P.; Bronson, Stefanie L.; Revello, Sonia; Bale, Tracy L.

    2013-01-01

    Neuropsychiatric disease frequently presents with an underlying hypo- or hyper- reactivity of the HPA stress axis, suggesting an exceptional vulnerability of this circuitry to external perturbations. Parental lifetime exposures to environmental challenges are associated with increased offspring neuropsychiatric disease risk, and likely contribute to stress dysregulation. While maternal influences have been extensively examined, much less is known regarding the specific role of paternal factors. To investigate the potential mechanisms by which paternal stress may contribute to offspring hypothalamic-pituitary-adrenal (HPA) axis dysregulation, we exposed mice to six weeks of chronic stress prior to breeding. As epidemiological studies support variation in paternal germ cell susceptibility to reprogramming across the lifespan, male stress exposure occurred either throughout puberty or in adulthood. Remarkably, offspring of sires from both paternal stress groups displayed significantly reduced HPA axis stress responsivity. Gene set enrichment analyses in offspring stress regulating brain regions, the paraventricular nucleus (PVN) and the bed nucleus of stria terminalis (BNST), revealed global pattern changes in transcription suggestive of epigenetic reprogramming and consistent with altered offspring stress responsivity, including increased expression of glucocorticoid-responsive genes in the PVN. In examining potential epigenetic mechanisms of germ cell transmission, we found robust changes in sperm miRNA (miR) content, where nine specific miRs were significantly increased in both paternal stress groups. Overall, these results demonstrate that paternal experience across the lifespan can induce germ cell epigenetic reprogramming and impact offspring HPA stress axis regulation, and may therefore offer novel insight into factors influencing neuropsychiatric disease risk. PMID:23699511

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

    PubMed

    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 upon the

  6. Short Term Exposure of Beta Cells to Low Concentrations of Interleukin-1β Improves Insulin Secretion through Focal Adhesion and Actin Remodeling and Regulation of Gene Expression*

    PubMed Central

    Arous, Caroline; Ferreira, Pedro G.; Dermitzakis, Emmanouil T.; Halban, Philippe A.

    2015-01-01

    Type 2 diabetes involves defective insulin secretion with islet inflammation governed in part by IL-1β. Prolonged exposure of islets to high concentrations of IL-1β (>24 h, 20 ng/ml) impairs beta cell function and survival. Conversely, exposure to lower concentrations of IL-1β for >24 h improves these same parameters. The impact on insulin secretion of shorter exposure times to IL-1β and the underlying molecular mechanisms are poorly understood and were the focus of this study. Treatment of rat primary beta cells, as well as rat or human whole islets, with 0.1 ng/ml IL-1β for 2 h increased glucose-stimulated (but not basal) insulin secretion, whereas 20 ng/ml was without effect. Similar differential effects of IL-1β depending on concentration were observed after 15 min of KCl stimulation but were prevented by diazoxide. Studies on sorted rat beta cells indicated that the enhancement of stimulated secretion by 0.1 ng/ml IL-1β was mediated by the NF-κB pathway and c-JUN/JNK pathway acting in parallel to elicit focal adhesion remodeling and the phosphorylation of paxillin independently of upstream regulation by focal adhesion kinase. Because the beneficial effect of IL-1β was dependent in part upon transcription, gene expression was analyzed by RNAseq. There were 18 genes regulated uniquely by 0.1 but not 20 ng/ml IL-1β, which are mostly involved in transcription and apoptosis. These results indicate that 2 h of exposure of beta cells to a low but not a high concentration of IL-1β enhances glucose-stimulated insulin secretion through focal adhesion and actin remodeling, as well as modulation of gene expression. PMID:25586177

  7. 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.

  8. 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

  9. Vimentin regulates differentiation switch via modulation of keratin 14 levels and their expression together correlates with poor prognosis in oral cancer patients.

    PubMed

    Dmello, Crismita; Sawant, Sharada; Alam, Hunain; Gangadaran, Prakash; Mogre, Saie; Tiwari, Richa; D'Souza, Zinia; Narkar, Manish; Thorat, Rahul; Patil, Komal; Chaukar, Devendra; Kane, Shubhada; Vaidya, Milind

    2017-01-01

    Vimentin is an intermediate filament protein, predominantly expressed in cells of mesenchymal origin, although its aberrant expression is seen in many carcinomas during epithelial mesenchymal transition. In cancer, vimentin expression is associated with the transition from a more differentiated epithelial phenotype to a dedifferentiated state. In view of the perceived role of keratins (Ks) as regulators of differentiation in epithelia, it was important to understand whether vimentin modulates differentiation through the reprogramming of keratins, in transformed cells. To address this, vimentin was stably downregulated in oral cancer derived cells. Further, global keratin profiling was performed after high salt keratin extraction. K5/K14 pair was found to be significantly downregulated, both at protein and mRNA levels upon vimentin downregulation. The previous study from our laboratory has shown a role of the K5/K14 pair in proliferation and differentiation of squamous epithelial cells. Vimentin depleted cells showed an increase in the differentiation state, marked by an increase in the levels of differentiation specific markers K1, involucrin, filaggrin and loricrin while its proliferation status remained unchanged. Rescue experiments with the K5/K14 pair overexpressed in vimentin knockdown background resulted in decreased differentiation state. ΔNp63 emerged as one of the indirect targets of vimentin, through which it modulates the expression levels of K5/K14. Further, immunohistochemistry showed a significant correlation between high vimentin-K14 expression and recurrence/poor survival in oral cancer patients. Thus, in conclusion, vimentin regulates the differentiation switch via modulation of K5/K14 expression. Moreover, vimentin-K14 together may prove to be the novel markers for the prognostication of human oral cancer.

  10. Vimentin regulates differentiation switch via modulation of keratin 14 levels and their expression together correlates with poor prognosis in oral cancer patients

    PubMed Central

    Dmello, Crismita; Sawant, Sharada; Alam, Hunain; Gangadaran, Prakash; Mogre, Saie; Tiwari, Richa; D’Souza, Zinia; Narkar, Manish; Thorat, Rahul; Patil, Komal; Chaukar, Devendra; Kane, Shubhada; Vaidya, Milind

    2017-01-01

    Vimentin is an intermediate filament protein, predominantly expressed in cells of mesenchymal origin, although its aberrant expression is seen in many carcinomas during epithelial mesenchymal transition. In cancer, vimentin expression is associated with the transition from a more differentiated epithelial phenotype to a dedifferentiated state. In view of the perceived role of keratins (Ks) as regulators of differentiation in epithelia, it was important to understand whether vimentin modulates differentiation through the reprogramming of keratins, in transformed cells. To address this, vimentin was stably downregulated in oral cancer derived cells. Further, global keratin profiling was performed after high salt keratin extraction. K5/K14 pair was found to be significantly downregulated, both at protein and mRNA levels upon vimentin downregulation. The previous study from our laboratory has shown a role of the K5/K14 pair in proliferation and differentiation of squamous epithelial cells. Vimentin depleted cells showed an increase in the differentiation state, marked by an increase in the levels of differentiation specific markers K1, involucrin, filaggrin and loricrin while its proliferation status remained unchanged. Rescue experiments with the K5/K14 pair overexpressed in vimentin knockdown background resulted in decreased differentiation state. ΔNp63 emerged as one of the indirect targets of vimentin, through which it modulates the expression levels of K5/K14. Further, immunohistochemistry showed a significant correlation between high vimentin-K14 expression and recurrence/poor survival in oral cancer patients. Thus, in conclusion, vimentin regulates the differentiation switch via modulation of K5/K14 expression. Moreover, vimentin-K14 together may prove to be the novel markers for the prognostication of human oral cancer. PMID:28225793

  11. H19 serves as a diagnostic biomarker and up-regulation of H19 expression contributes to poor prognosis in patients with gastric cancer.

    PubMed

    Chen, J S; Wang, Y F; Zhang, X Q; Lv, J M; Li, Y; Liu, X X; Xu, T P

    2016-01-01

    Emerging evidences indicate that dysregulated long noncoding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be used as diagnosis and prognosis biomarker, or potential therapeutic targets. LncRNA H19 has been reported to be upregulated in diverse human cancers; however, its clinical significance in gastric cancer (GC) remains elusive. Expression levels of H19 in 128 pairs of GC and adjacent normal tissues, GC cell lines and GC juices compared to their corresponding controls were detected by real-time quantitative polymerase chain reaction (qPCR) assay. A receiver operating characteristic (ROC) curve and Kaplan-Meier analysis were constructed to evaluate the diagnostic and prognostic values. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. H19 expression was remarkably increased in GC tissues and cell lines compared with that in the normal control, and its up-regulation was significantly correlated to invasion depth (P < 0.001), advanced TNM stage (P = 0.002) and regional lymph nodes metastasis (P < 0.001) in GC. H19 levels were robust in differentiating GC tissues from controls [area under the curve (AUC) = 0.697; 95% confidence interval (CI) = 0.636-0.752, p<0.01]. Kaplan-Meier analysis demonstrated that increased H19 expression contributed to poor overall survival (P = 0.017) and disease-free survival (P = 0.024) of patients. A multivariate survival analysis also indicated that H19 could be an independent prognostic marker. The levels of H19 in gastric juice from gastric patients were significantly higher than those from normal subjects (P = 0.034). Furthermore, knockdown of H19 expression by siRNA could inhibit cell migration and invasion in GC cells partly via regulating E-cadherin protein expression. H19 might serve as a promising biomarker for early detection and prognosis prediction of GC.

  12. 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

  13. 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

  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 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

  15. 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.

  16. 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.

  17. 14-3-3ζ regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function

    PubMed Central

    Schoenwaelder, Simone M.; Darbousset, Roxane; Cranmer, Susan L.; Ramshaw, Hayley S.; Orive, Stephanie L.; Sturgeon, Sharelle; Yuan, Yuping; Yao, Yu; Krycer, James R.; Woodcock, Joanna; Maclean, Jessica; Pitson, Stuart; Zheng, Zhaohua; Henstridge, Darren C.; van der Wal, Dianne; Gardiner, Elizabeth E.; Berndt, Michael C.; Andrews, Robert K.; James, David E.; Lopez, Angel F.; Jackson, Shaun P.

    2016-01-01

    The 14-3-3 family of adaptor proteins regulate diverse cellular functions including cell proliferation, metabolism, adhesion and apoptosis. Platelets express numerous 14-3-3 isoforms, including 14-3-3ζ, which has previously been implicated in regulating GPIbα function. Here we show an important role for 14-3-3ζ in regulating arterial thrombosis. Interestingly, this thrombosis defect is not related to alterations in von Willebrand factor (VWF)–GPIb adhesive function or platelet activation, but instead associated with reduced platelet phosphatidylserine (PS) exposure and procoagulant function. Decreased PS exposure in 14-3-3ζ-deficient platelets is associated with more sustained levels of metabolic ATP and increased mitochondrial respiratory reserve, independent of alterations in cytosolic calcium flux. Reduced platelet PS exposure in 14-3-3ζ-deficient mice does not increase bleeding risk, but results in decreased thrombin generation and protection from pulmonary embolism, leading to prolonged survival. Our studies define an important role for 14-3-3ζ in regulating platelet bioenergetics, leading to decreased platelet PS exposure and procoagulant function. PMID:27670677

  18. AB245. Down-regulation of C12orf59 is associated with a poor prognosis and VHL mutations in renal cell carcinoma

    PubMed Central

    Li, Zesong; Xie, Jun; Zhu, Chuangzhi

    2016-01-01

    Background The aim of this study was to investigate the expression and prognostic value of C12orf59 in ccRCC. Methods In silico gene expression was performed to analyze C12orf59 mRNA expression. The mRNA and protein expression levels of C12orf59 were assessed by real-time PCR and western blotting in a panel of cancer cell lines and 40 paired primary RCC and corresponding adjacent noncancerous tissues. Immunohistochemistry on additional renal tumor tissues was performed to study the C12orf59 expression and its association with clinico-pathological parameters (n=204), disease outcomes, the VHL gene, the UMPP gene and chromatin remodeling gene mutations (n=86), and HIF1α and HIF2α protein levels (n=86). Results C12orf59 mRNA was broadly expressed in normal human tissues with high expression levels in the kidney, and the C12orf59 protein was located in the cytoplasm. A panel of cancer cell lines lacked detectable C12orf59 expression, and C12orf59 expression was significantly down-regulated in renal cell carcinoma (RCC) compared with corresponding adjacent noncancerous tissues (P<0.01). The loss of C12orf59 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). Conclusions C12orf59 expression was significantly down-regulated in RCC, and C12orf59 may serve as a prognostic biomarker of ccRCC with potential applications as a target for future functional studies. Decreased C12orf59 expression is associated with the loss of VHL and may cooperate with the loss of VHL to promote renal carcinogenesis.

  19. 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

  20. Organic carbon, and major and trace element dynamic and fate in a large river subjected to poorly-regulated urban and industrial pressures (Sebou River, Morocco).

    PubMed

    Hayzoun, H; Garnier, C; Durrieu, G; Lenoble, V; Le Poupon, C; Angeletti, B; Ouammou, A; Mounier, S

    2015-01-01

    An annual-basis study of the impacts of the anthropogenic inputs from Fez urban area on the water geochemistry of the Sebou and Fez Rivers was conducted mostly focusing on base flow conditions, in addition to the sampling of industrial wastewater characteristic of the various pressures in the studied environment. The measured trace metals dissolved/particulate partitioning was compared to the ones predicted using the WHAM-VII chemical speciation code. The Sebou River, upstream from Fez city, showed a weakly polluted status. Contrarily, high levels of major ions, organic carbon and trace metals were encountered in the Fez River and the Sebou River downstream the Fez inputs, due to the discharge of urban and industrial untreated and hugely polluted wastewaters. Trace metals were especially enriched in particles with levels even exceeding those recorded in surface sediments. The first group of elements (Al, Fe, Mn, Ti, U and V) showed strong inter-relationships, impoverishment in Fez particles/sediments and stable partition coefficient (Kd), linked to their lithogenic origin from Sebou watershed erosion. Conversely, most of the studied trace metals/metalloids, originated from anthropogenic sources, underwent significant changes of Kd and behaved non-conservatively in the Sebou/Fez water mixing. Dissolved/particulate partitioning was correctly assessed by WHAM-VII modeling for Cu, Pb and Zn, depicting significant differences in chemical speciation in the Fez River when compared to that in the Sebou River. The results of this study demonstrated that a lack of compliance in environmental regulations certainly explained this poor status.

  1. Exposure to cell phone radiation up-regulates apoptosis genes in primary cultures of neurons and astrocytes.

    PubMed

    Zhao, Tian-Yong; Zou, Shi-Ping; Knapp, Pamela E

    2007-01-22

    The health effects of cell phone radiation exposure are a growing public concern. This study investigated whether expression of genes related to cell death pathways are dysregulated in primary cultured neurons and astrocytes by exposure to a working Global System for Mobile Communication (GSM) cell phone rated at a frequency of 1900MHz. Primary cultures were exposed to cell phone emissions for 2h. We used array analysis and real-time RT-PCR to show up-regulation of caspase-2, caspase-6 and Asc (apoptosis associated speck-like protein containing a card) gene expression in neurons and astrocytes. Up-regulation occurred in both "on" and "stand-by" modes in neurons, but only in "on" mode in astrocytes. Additionally, astrocytes showed up-regulation of the Bax gene. The effects are specific since up-regulation was not seen for other genes associated with apoptosis, such as caspase-9 in either neurons or astrocytes, or Bax in neurons. The results show that even relatively short-term exposure to cell phone radiofrequency emissions can up-regulate elements of apoptotic pathways in cells derived from the brain, and that neurons appear to be more sensitive to this effect than astrocytes.

  2. 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.

  3. Functional changes after prenatal opiate exposure related to opiate receptors' regulated alterations in cholinergic innervation.

    PubMed

    Yanai, Joseph; Huleihel, Rabab; Izrael, Michal; Metsuyanim, Sally; Shahak, Halit; Vatury, Ori; Yaniv, Shiri P

    2003-09-01

    Opioid drugs act primarily on the opiate receptors; they also exert their effect on other innervations resulting in non-opioidergic behavioural deficits. Similarly, opioid neurobehavioural teratogenicity is attested in numerous behaviours and neural processes which hinder the research on the mechanisms involved. Therefore, in order to be able to ascertain the mechanism we have established an animal (mouse) model for the teratogenicity induced by opioid abuse, which focused on behaviours related to specific brain area and innervation. Diacetylmorphine (heroin) and not morphine was applied because heroin exerts a unique action, distinguished from that of morphine. Pregnant mice were exposed to heroin (10 mg/kg per day) and the offspring were tested for behavioural deficits and biochemical alterations related to the septohippocampal cholinergic innervation. Some studies employing the chick embryo were concomitantly added as a control for the confounding indirect variables. Prenatal exposure to heroin in mice induced global hyperactivation both pre- and post-synaptic along the septohippocampal cholinergic innervation, including basal protein kinase C (PKC) activity accompanied by a desensitization of PKC activity in response to cholinergic agonist. Functionally, the heroin-exposed offspring displayed deficits in hippocampus-related behaviours, suggesting deficits in the net output of the septohippocampal cholinergic innervation. Grafting of cholinergic cells to the impaired hippocampus reversed both pre- and post-synaptic hyperactivity, resensitized PKC activity, and restored the associated behaviours to normality. Consistently, correlation studies point to the relative importance of PKC to the behavioural deficits. The chick model, which dealt with imprinting related to a different brain region, confirmed that the effect of heroin is direct. Taken together with studies by others on the effect of prenatal exposure to opioids on the opioidergic innervation and with what

  4. 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.

  5. Exposure to Cell Phone Radiation Up-Regulates Apoptosis Genes in Primary Cultures of Neurons and Astrocytes

    PubMed Central

    Zhao, Tian-Yong; Zou, Shi-Ping; Knapp, Pamela E.

    2007-01-01

    The health effects of cell phone radiation exposure are a growing public concern. This study investigated whether expression of genes related to cell death pathways are dysregulated in primary cultured neurons and astrocytes by exposure to a working GSM (Global System for Mobile Communication) cell phone rated at a frequency of 1900 MHz. Primary cultures were exposed to cell phone emissions for 2 hrs. We used array analysis and real-time RT-PCR to show up-regulation of caspase-2, caspase-6 and Asc (apoptosis associated speck-like protein containing a card) gene expression in neurons and astrocytes. Upregulation occurred in both “on” and “stand-by” modes in neurons, but only in “on” mode in astrocytes. Additionally, astrocytes showed up-regulation of the Bax gene. The effects are specific since up-regulation was not seen for other genes associated with apoptosis, such as caspase-9 in either neurons and astrocytes, or Bax in neurons. The results show that even relatively short-term exposure to cell phone radiofrequency emissions can up-regulate elements of apoptotic pathways in cells derived from the brain, and that neurons appear to be more sensitive to this effect than astrocytes. PMID:17187929

  6. Regulation of L1 expression and retrotransposition by melatonin and its receptor: implications for cancer risk associated with light exposure at night.

    PubMed

    deHaro, Dawn; Kines, Kristine J; Sokolowski, Mark; Dauchy, Robert T; Streva, Vincent A; Hill, Steven M; Hanifin, John P; Brainard, George C; Blask, David E; Belancio, Victoria P

    2014-07-01

    Expression of long interspersed element-1 (L1) is upregulated in many human malignancies. L1 can introduce genomic instability via insertional mutagenesis and DNA double-strand breaks, both of which may promote cancer. Light exposure at night, a recently recognized carcinogen, is associated with an increased risk of cancer in shift workers. We report that melatonin receptor 1 inhibits mobilization of L1 in cultured cells through downregulation of L1 mRNA and ORF1 protein. The addition of melatonin receptor antagonists abolishes the MT1 effect on retrotransposition in a dose-dependent manner. Furthermore, melatonin-rich, but not melatonin-poor, human blood collected at different times during the circadian cycle suppresses endogenous L1 mRNA during in situ perfusion of tissue-isolated xenografts of human cancer. Supplementation of human blood with exogenous melatonin or melatonin receptor antagonist during the in situ perfusion establishes a receptor-mediated action of melatonin on L1 expression. Combined tissue culture and in vivo data support that environmental light exposure of the host regulates expression of L1 elements in tumors. Our data imply that light-induced suppression of melatonin production in shift workers may increase L1-induced genomic instability in their genomes and suggest a possible connection between L1 activity and increased incidence of cancer associated with circadian disruption.

  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.

  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.

  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. Down-regulation of Decapping Protein 2 mediates chronic nicotine exposure-induced locomotor hyperactivity in Drosophila.

    PubMed

    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.

  11. Regulation of the Na+/K(+)-ATPase pump in vitro after long-term exposure to cocaine: role of serotonin.

    PubMed

    Mackler, S A; Kleyman, T R; Cha, X Y

    1998-05-01

    Long-term exposure to cocaine can cause persistent behavioral changes and alterations in neuronal function. One cocaine-regulated mRNA in the rat brain is the beta-1 subunit of the Na+/K(+)-ATPase pump. We examined both Na+/K(+)-ATPase function and expression after cocaine treatment of pheochromocytoma cells. One-hour exposure to cocaine did not alter Na+/K(+)-ATPase activity, as measured by the ouabain-sensitive component of rubidium uptake. Four days of cocaine resulted in an approximately 30% decrease in Na+/K(+)-ATPase activity. Western blot analyses demonstrated an approximately 25% decrease in levels of the beta-1 isoform, without changes in pump total alpha subunit levels. Treatment with dopamine type 1 or type 2 receptor agonists for the same period did not affect Na+/K(+)-ATPase activity. The serotonin-selective reuptake inhibitor paroxetine caused an approximately 45% decrease in rubidium uptake after 4 days, whereas pump function was not altered after treatment with either the dopamine-selective reuptake blocker nomifensine or the norepinephrine-selective reuptake blocker desipramine. Chronic treatment with both cocaine and LY 278,584, a serotonin type 3 receptor antagonist, did not replicate the cocaine-associated decrease in pump function. Long-term cocaine exposure regulates expression and function of the Na+/K(+)-ATPase pump in neuronal-like cells; this regulation is mediated in part via the serotonin type 3 receptor. Similar Na+/K(+)-ATPase pump regulation in vivo may selectively alter neuronal function in the mammalian brain.

  12. Differential regulation of intracellular factors mediating cell cycle, DNA repair and inflammation following exposure to silver nanoparticles in human cells

    PubMed Central

    2012-01-01

    Background Investigating the cellular and molecular signatures in eukaryotic cells following exposure to nanoparticles will further our understanding on the mechanisms mediating nanoparticle induced effects. This study illustrates the molecular effects of silver nanoparticles (Ag-np) in normal human lung cells, IMR-90 and human brain cancer cells, U251 with emphasis on gene expression, induction of inflammatory mediators and the interaction of Ag-np with cytosolic proteins. Results We report that silver nanoparticles are capable of adsorbing cytosolic proteins on their surface that may influence the function of intracellular factors. Gene and protein expression profiles of Ag-np exposed cells revealed up regulation of many DNA damage response genes such as Gadd 45 in both the cell types and ATR in cancer cells. Moreover, down regulation of genes necessary for cell cycle progression (cyclin B and cyclin E) and DNA damage response/repair (XRCC1 and 3, FEN1, RAD51C, RPA1) was observed in both the cell lines. Double strand DNA damage was observed in a dose dependant manner as evidenced in γH2AX foci assay. There was a down regulation of p53 and PCNA in treated cells. Cancer cells in particular showed a concentration dependant increase in phosphorylated p53 accompanied by the cleavage of caspase 3 and PARP. Our results demonstrate the involvement of NFκB and MAP kinase pathway in response to Ag-np exposure. Up regulation of pro-inflammatory cytokines such as interleukins (IL-8, IL-6), macrophage colony stimulating factor, macrophage inflammatory protein in fibroblasts following Ag-np exposure were also observed. Conclusion In summary, Ag-np can modulate gene expression and protein functions in IMR-90 cells and U251 cells, leading to defective DNA repair, proliferation arrest and inflammatory response. The observed changes could also be due to its capability to adsorb cytosolic proteins on its surface. PMID:22321936

  13. Marijuana and tobacco exposure predict affect-regulation expectancies in dual users.

    PubMed

    Martens, K M; Gilbert, David G

    2008-11-01

    In order to better compare affect-related expectancies for tobacco and marijuana smoking, associations of marijuana and tobacco exposure to negative affect reduction (NAR), positive affect enhancement (PAE), and related smoking outcome expectancies were assessed in young individuals who reported smoking both marijuana and tobacco on a regular basis (dual users). More frequent smoking of a given substance was associated with expectations of greater NAR and PAE by that substance while duration of exposure did not reliably predict NAR or PAE drug expectancies. Contrary to expectations, individuals anticipating greater NAR and/or PAE for one substance did not exhibit corresponding expectancies for the other drug. These findings suggest that exposure duration may be less important than current usage levels in influencing affect expectancies and that the affect-related expectancies for tobacco and marijuana are largely independent of each other.

  14. Early life antibiotic exposure affects pancreatic islet development and metabolic regulation

    PubMed Central

    Li, Jiaying; Yang, Kaiyuan; Ju, Tingting; Ho, Tracy; McKay, Catharine A.; Gao, Yanhua; Forget, Shay K.; Gartner, Stephanie R.; Field, Catherine J.; Chan, Catherine B.; Willing, Benjamin P.

    2017-01-01

    Childhood antibiotic exposure has been recently linked with increased risk of metabolic disease later in life. A better understanding of this association would potentially provide strategies to reduce the childhood chronic disease epidemic. Therefore, we explored the underlying mechanisms using a swine model that better mimics human infants than rodents, and demonstrated that early life antibiotic exposure affects glucose metabolism 5 weeks after antibiotic withdrawal, which was associated with changes in pancreatic development. Antibiotics exerted a transient impact on postnatal gut microbiota colonization and microbial metabolite production, yet changes in the expression of key genes involved in short-chain fatty acid signaling and pancreatic development were detected in later life. These findings suggest a programming effect of early life antibiotic exposure that merits further investigation. PMID:28150721

  15. Molecular identification and expression of differentially regulated genes of the European flounder, Platichthys flesus, submitted to pesticide exposure.

    PubMed

    Marchand, J; Tanguy, A; Charrier, G; Quiniou, L; Plee-Gauthier, E; Laroche, J

    2006-01-01

    Effects of pesticide exposure on the European flounder, Platichthys flesus, were investigated using a suppression subtractive hybridization method (SSH) to identify up- and down-regulated genes after a 30-day exposure to herbicides (a cocktail of atrazine, diuron, and isoproturon, and a single herbicide, glyphosate). A total of 256 expressed gene sequences were identified as having the potential for being differentially expressed, of which 116 could be identified by homology with databased sequences. The metabolic functions with which they are associated include energy production, general metabolism, signaling, transport, immune system, and structure. Expression of 14 of these genes was analyzed in liver, muscle, and gills by reverse transcriptase-polymerase chain reaction (RT-PCR) under experimental conditions (0, 15, and 30 days of exposure) and under field conditions (sampling in two estuaries displaying different levels of pesticide contamination). This study provides a first basis for studying the response of fish to pesticide exposure and allows the characterization of new potential genetic markers of pesticide contamination in the field.

  16. Impact of gamma rays exposure and growth regulators on Oryza sativa L. c.v MR269 callus induction

    NASA Astrophysics Data System (ADS)

    Kadhimi, Ahsan A.; Zain, Che Radziah Che Mohd; Alhasnawi, Arshad Naji; Isahak, Anizan; Ashraf, Mehdi Farshad; Mohamad, Azhar; Doni, Febri; Yusoff, Wan Mohtar Wan

    2016-11-01

    The study is aimed to evaluate in vitro somatic embryogenesis to gamma ray exposure and the use of growth regulators to mature embryos explants for rice callus induction. Seeds of local rice genotype (MR269) were exposed to gamma rays at 350 Gy (Source: Caesium-137). Matured embryos were cultured to induce callus on Murashige and Skoog (MS) supplemented at different concentrations of 1.0, 2.0, 3.0 mg/L 2.4-D and 0.1 and 0.2 mg/L Kinetin for 4 weeks. Callus induction and callus fresh weight were decreased after exposure to gamma ray. The most efficient response to callus induction and callus fresh weight was found at 3 mg/L 2,4-D and 0.1 mg/L kinetin.

  17. Lead hazards for pregnant women and children: part 1: immigrants and the poor shoulder most of the burden of lead exposure in this country. Part 1 of a two-part article details how exposure happens, whom it affects, and the harm it can do.

    PubMed

    Cleveland, Lisa M; Minter, Monica L; Cobb, Kathleen A; Scott, Anthony A; German, Victor F

    2008-10-01

    Poor, urban, and immigrant populations are at far greater risk for lead exposure than are other groups in the United States. Children with even slightly elevated blood lead levels are at increased risk for significant neurobehavioral problems that can extend through adolescence. Research has shown that elevated blood lead levels in pregnant women, even those well below 10 micrograms per deciliter-the Centers for Disease Control and Prevention's "level of concern"-can cause miscarriage, premature birth, low birth weight, and subsequent developmental delays in their children. Despite these well-established dangers, routine prenatal lead screening and lead education is not a standard of care. Part 1 of this two-part article presents a short case example of a pregnant mother with lead poisoning and describes the epidemiology of lead exposure in the United States, the main sources of lead exposure, and the effects of lead on the pregnant mother and the developing fetus and child. Prevention is crucial. Treatment options such as chelation must be used selectively and will not reverse damage once it's occurred. Part 2 will describe recommendations for screening, education, nutrition, reducing environmental exposures, and treatment.

  18. 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.

  19. 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...

  20. 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…

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

    PubMed Central

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

    2015-01-01

    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

  2. Down-regulation of tumor suppressor gene PTEN, overexpression of p53, plus high proliferating cell nuclear antigen index predict poor patient outcome of hepatocellular carcinoma after resection.

    PubMed

    Hu, Tsung-Hui; Wang, Chih-Chi; Huang, Chao-Cheng; Chen, Chao-Long; Hung, Chao-Hung; Chen, Chien-Hung; Wang, Jing-Houng; Lu, Sheng-Nan; Lee, Chuan-Mo; Changchien, Chi-Sin; Tai, Ming-Hong

    2007-12-01

    We aimed to evaluate the interaction of two tumor suppressor genes PTEN and p53 and their relationship with cell cycle protein proliferating cell nuclear antigen (PCNA) in hepatocellular carcinoma (HCC). A total of 124 resected HCC paraffin specimens were collected from 1987 to 1999 for immunohistochemistry. Expression of PTEN, p53 and PCNA in HCC were analyzed for clinicopathologic correlation. The study revealed decreased or absent PTEN immunostaining (PTEN down-regulation) in 42.7% and positive p53 (p53+) immunostaining in 41.9% of HCC. There was a positive correlation between PTEN down-regulation and p53 (+) (P=0.001). PTEN down-regulation or p53 (+) correlated with increased HCC dedifferentiation, advanced pathologic stages and high PCNA labeling index (LI) of tumors (P<0.05). Patients with either PTEN down-regulation, p53 (+), or high PCNA LI had shorter survival and higher recurrence rates than patients with intact PTEN expression, p53 (-), or low PCNA LI respectively (P<0.05). By combining the three genes, patients with all PTEN down-regulation (+)/p53 (+)/high PCNA LI had the shortest overall survival (P<0.001) and the highest recurrence rates (P<0.001), followed by patients with two, one and none of three events accordingly. Combination of PTEN/p53/PCNA represented an independent prognostic factor for tumor recurrence and disease-specific survival (P<0.05). In conclusion, the down-regulated PTEN expression and p53 over-expression are involved in the pathogenesis of HCC. They correlate with high PCNA expression, HCC de-differentiation and advanced HCC stages. A combination of the three genes predicts patient outcome more powerfully than any of the individual genes.

  3. Regulation of xenobiotic transporter genes in liver and brain of juvenile thicklip grey mullets (Chelon labrosus) after exposure to Prestige-like fuel oil and to perfluorooctane sulfonate.

    PubMed

    de Cerio, Oihane Diaz; Bilbao, Eider; Cajaraville, Miren P; Cancio, Ibon

    2012-04-25

    Xenobiotic transport proteins are involved in cellular defence against accumulation of xenobiotics participating in multixenobiotic resistance (MXR). In order to study the transcriptional regulation of MXR genes in fish exposed to common chemical pollutants we selected the thicklip grey mullet (Chelon labrosus), since mugilids are widespread in highly degraded estuarine environments where they have to survive through development and adulthood. Partial sequences belonging to genes coding for members of 3 different families of ATP binding cassette (ABC) transporter proteins (ABCB1; ABCB11; ABCC2; ABCC3; ABCG2) and a vault protein (major vault protein, MVP) were amplified and sequenced from mullet liver. Their liver and brain transcription levels were examined in juvenile mullets under exposure to perfluorooctane sulfonate (PFOS) and to fresh (F) and weathered (WF) Prestige-like heavy fuel oil for 2 and 16 days. In liver, PFOS significantly up-regulated transcription of abcb1, abcb11 and abcg2 while in brain only abcb11 was up-regulated. Both fuel treatments significantly down-regulated abcb11 in liver at day 2 while abcc2 was only down-regulated by WF. mvp was significantly up-regulated by F and down-regulated by WF at day 2 in the liver. At day 16 only a significant up-regulation of abcb1 in the F group was recorded. Brain abcc3 and abcg2 were down-regulated by both fuels at day 2, while abcb1 and abcc2 were only down-regulated by F exposure. After 16 days of exposure only abcb11 and abcg2 were regulated. In conclusion, exposure to organic xenobiotics significantly alters transcription levels of genes participating in xenobiotic efflux, especially after short periods of exposure. Efflux transporter gene transcription profiling could thus constitute a promising tool to assess exposure to common pollutants.

  4. 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

  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. Cadmium exposure disrupts GABA and taurine regulation of prolactin secretion in adult male rats.

    PubMed

    Caride, A; Fernández-Pérez, B; Cabaleiro, T; Esquifino, A I; Lafuente, A

    2009-03-28

    This work was undertaken to evaluate the possible effects of cadmium exposure on 24 h changes of gamma-aminobutyric acid (GABA) and taurine median eminence and pituitary contents. Also the possible alterations of the regulatory mechanisms of GABA and taurine on prolactin secretion were evaluated. Adult male rats were given cadmium at a dose of 25 mg/l of cadmium chloride in the drinking water for 30 days. Control age-matched rats received cadmium free water. Metal exposure induced the appearance of a maximal value of prolactin at 08:00 h. In median eminence, cadmium abolished the GABA and taurine maximal values and decreased GABA and taurine mean levels. In the anterior pituitary, cadmium treatment phase advanced 12 h the peak observed in controls at 00:00 h for both amino acids. There was a positive correlation between GABA and taurine contents in median eminence and the anterior pituitary in both control and cadmium-exposed animals. However, the correlation between GABA or/and taurine with prolactin levels disappeared in cadmium-exposed animals. These results suggest that cadmium exposure affects GABA and taurine daily pattern in the median eminence and anterior pituitary, and those changes explain, at least in part, the modification in the regulatory pattern of prolactin secretion.

  7. 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

  8. Acute transcriptional up-regulation specific to osteoblasts/osteoclasts in medaka fish immediately after exposure to microgravity

    PubMed Central

    Chatani, Masahiro; Morimoto, Hiroya; Takeyama, Kazuhiro; Mantoku, Akiko; Tanigawa, Naoki; Kubota, Koji; Suzuki, Hiromi; Uchida, Satoko; Tanigaki, Fumiaki; Shirakawa, Masaki; Gusev, Oleg; Sychev, Vladimir; Takano, Yoshiro; Itoh, Takehiko; Kudo, Akira

    2016-01-01

    Bone loss is a serious problem in spaceflight; however, the initial action of microgravity has not been identified. To examine this action, we performed live-imaging of animals during a space mission followed by transcriptome analysis using medaka transgenic lines expressing osteoblast and osteoclast-specific promoter-driven GFP and DsRed. In live-imaging for osteoblasts, the intensity of osterix- or osteocalcin-DsRed fluorescence in pharyngeal bones was significantly enhanced 1 day after launch; and this enhancement continued for 8 or 5 days. In osteoclasts, the signals of TRAP-GFP and MMP9-DsRed were highly increased at days 4 and 6 after launch in flight. HiSeq from pharyngeal bones of juvenile fish at day 2 after launch showed up-regulation of 2 osteoblast- and 3 osteoclast- related genes. Gene ontology analysis for the whole-body showed that transcription of genes in the category “nucleus” was significantly enhanced; particularly, transcription-regulators were more up-regulated at day 2 than at day 6. Lastly, we identified 5 genes, c-fos, jun-B-like, pai-1, ddit4 and tsc22d3, which were up-regulated commonly in the whole-body at days 2 and 6, and in the pharyngeal bone at day 2. Our results suggested that exposure to microgravity immediately induced dynamic alteration of gene expression levels in osteoblasts and osteoclasts. PMID:28004797

  9. Down-regulation of sup 3 H-imipramine binding sites in rat cerebral cortex prenatal exposure to antidepressants

    SciTech Connect

    Montero, D.; de Ceballos, M.L. ); Del Rio, J. )

    1990-01-01

    Several antidepressant drugs were given to pregnant rats in the last 15 days of gestation and {sup 3}H-imipramine binding ({sup 3}H-IMI) was subsequently measured in the cerebral cortex of the offspring. The selective serotonin (5-HT) uptake blockers chlorimipramine and fluoxetine as well as the selective monoamine oxidase (MAO) inhibitors clorgyline and deprenyl induced, after prenatal exposure, a down-regulation of {sup 3}H-IMI binding sites at postnatal day 25. The density of these binding sites was still reduced at postnatal day 90 in rats exposed in utero to the MAO inhibitors. The antidepressants desipramine and nomifensine were ineffective in this respect. After chronic treatment of adult animals, only chlorimipramine was able to down-regulate the {sup 3}H-IMI binding sites. Consequently, prenatal exposure of rats to different antidepressant drugs affecting predominantly the 5-HT systems induces more marked and long-lasting effects on cortical {sup 3}H-IMI binding sites. The results suggest that the developing brain is more susceptible to the actions of antidepressants.

  10. Influence of repeated daily menthol exposure on human temperature regulation and perception.

    PubMed

    Gillis, D Jason; Weston, Neil; House, James R; Tipton, Michael J

    2015-02-01

    A single exposure to menthol can, depending on concentration, enhance both cool sensations and encourage body heat storage. This study tested whether there is an habituation in either response after repeated-daily exposures. Twenty-two participants were assigned to one of three spray groups: Control (CON; n=6), 0.05% L-menthol (M(0.05%); n=8), and 0.2% L-menthol (M(0.2%); n=8). On Monday (20°C, 50% rh) participants were sprayed with 100 mL of solution and undertook 40 min of cycling at 45% of their peak power (Ex1), from Tuesday to Thursday (30°C, 50% rh) they were sprayed twice daily whilst resting (R1 to R6), Friday was a repeat of Monday (Ex2). Thermal sensation (TS), thermal comfort, perceived exertion, irritation, rectal and skin temperature (Tsk), skin blood flow (SkBF) and sweat rate were monitored. A two-way ANOVA (alpha=0.05) compared responses from the beginning (Ex1, R1) and end (Ex2, R5) of the testing week. M(0.2%) induced significantly (P<0.05) cooler TS at the beginning of the week (Ex1, R1) compared to the end (Ex2, R5), indicating habituation of TS; this was not observed in M(0.05%). No other perceptual or physiological responses habituated. 0.2% Menthol caused a heat storage response, mediated by vasoconstriction, at the beginning and end of the week, suggesting the habituation of TS occurred in a pathway specific to sensation. In summary, the cooling influence of 0.2% menthol habituates after repeated-daily exposures, but with no habituation in heat storage.

  11. Epigenetic Alterations May Regulate Temporary Reversal of CD4+ T Cell Activation Caused by Trichloroethylene Exposure

    PubMed Central

    Gilbert, Kathleen M.; Nelson, Ashley R.; Cooney, Craig A.; Reisfeld, Brad; Blossom, Sarah J.

    2012-01-01

    Previous studies have shown that short-term (4 weeks) or chronic (32 weeks) exposure to trichloroethylene (TCE) in drinking water of female MRL+/+ mice generated CD4+ T cells that secreted increased levels of interferon (IFN)-γ and expressed an activated (CD44hiCD62Llo) phenotype. In contrast, the current study of subchronic TCE exposure showed that midway in the disease process both of these parameters of CD4+ T cell activation were reversed. This phase of the disease process may represent an attempt by the body to counteract the inflammatory effects of TCE. The decrease in CD4+ T cell production of IFN-γ following subchronic TCE exposure could not be attributed to skewing toward a Th2 or Th17 phenotype or to an increase in Treg cells. Instead, the suppression corresponded to alterations in markers used to assess DNA methylation, namely increased expression of retrotransposons Iap (intracisternal A particle) and Muerv (murine endogenous retrovirus). Also observed was an increase in the expression of Dnmt1 (DNA methyltransferase-1) and decreased expression of several genes known to be downregulated by DNA methylation, namely Ifng, Il2, and Cdkn1a. CD4+ T cells from a second study in which MRL+/+ mice were treated for 17 weeks with TCE showed a similar increase in Iap and decrease in Cdkn1a. In addition, DNA collected from the CD4+ T cells in the second study showed TCE-decreased global DNA methylation. Thus, these results described the biphasic nature of TCE-induced alterations in CD4+ T cell function and suggested that these changes represented potentially reversible alterations in epigenetic processes. PMID:22407948

  12. 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…

  13. 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...

  14. Growth inhibition and coordinated physiological regulation of zebrafish (Danio rerio) embryos upon sublethal exposure to antidepressant amitriptyline.

    PubMed

    Yang, Ming; Qiu, Wenhui; Chen, Jingsi; Zhan, Jing; Pan, Chenyuan; Lei, Xiangjie; Wu, Minghong

    2014-06-01

    Amitriptyline is a tricyclic antidepressant used for decades. It is present at low detectable concentrations in the aquatic environment, but relative few studies have focused on its ecotoxicological effects on non-target aquatic animals. The present study conducted an acute toxicity test of waterborne amitriptyline exposure using zebrafish (Danio rerio) embryos 4 to 124 h-post-fertilization. Time-dependent lethal concentrations were firstly determined and at mg/L levels. Effects of amitriptyline on zebrafish embryos were then evaluated under amitriptyline exposure at sublethal concentrations of 1, 10, 100 ng/L, 1, 10, 100 μg/L and 1mg/L. Our results showed that amitriptyline significantly reduced the hatching time and body length of embryos after exposure in a concentration-dependent manner. Our study also revealed that the exposure evoked a coordinated modulation of physiological and biochemical parameters in exposed zebrafish embryos, including alterations of adrenocorticotropic hormone (ACTH) level, oxidative stress and antioxidant parameters, as well as nitric oxide (NO) production and total nitric oxide synthase (TNOS) activity. A U-shaped concentration-dependent response curve was observed in ACTH level in response to amitriptyline exposure. However, both U-shaped and inversed U-shaped curves were indicated in the responses of antioxidant parameters, including total antioxidant capacity, antioxidant enzyme activities (catalase, superoxide dismutase and peroxidase), glutathione content and glutathione reductase activity. Correspondingly, hydroxyl radical formation and lipid peroxidation indices changed in similar U-shaped concentration-dependent patterns, which together the results of antioxidant parameters suggested induction of oxidative stress in embryos exposed to amitriptyline at high concentrations. Moreover, NO production and TNOS activity were both significantly affected by amitriptyline exposure. Notably, significant correlations between these

  15. Up-regulation of neurotrophin-related gene expression in mouse hippocampus following low-level toluene exposure.

    PubMed

    Win-Shwe, Tin-Tin; Tsukahara, Shinji; Yamamoto, Shoji; Fukushima, Atsushi; Kunugita, Naoki; Arashidani, Keiichi; Fujimaki, Hidekazu

    2010-01-01

    To investigate the role of strain differences in sensitivity to low-level toluene exposure on neurotrophins and their receptor levels in the mouse hippocampus, 8-week-old male C3H/HeN, BALB/c and C57BL/10 mice were exposed to 0, 5, 50, or 500 ppm toluene for 6h per day, 5 days per week for 6 weeks in an inhalation chamber. We examined the expressions of neurotrophin-related genes and receptors in the mouse hippocampus using real-time reverse transcription polymerase chain reaction (RT-PCR). The expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tyrosine kinase (Trk) A, and TrkB mRNAs in the C3H/HeN mice hippocampus was significantly higher in the mice exposed to 500 ppm toluene. Among the three strains of mice, the C3H/HeN mice seemed to be sensitive to toluene exposure. To examine the combined effect of toluene exposure and allergic challenge, the C3H/HeN mice stimulated with ovalbumin were exposed to toluene. The allergy group of C3H/HeN mice showed significantly elevated level of NGF mRNA in the hippocampus following exposure to 50 ppm toluene. Then, we also examined the expression of transcription factor, dopamine markers and oxidative stress marker in the hippocampus of sensitive strain C3H/HeN mice and found that the expression of CREB1 mRNA was significantly increased at 50 ppm toluene. In immunohistochemical analysis, the density of the NGF-immunoreactive signal was significantly stronger in the hippocampal CA3 region of the C3H/HeN mice exposed to 500 ppm toluene in non-allergy group and 50 ppm in allergy group. Our results indicate that low-level toluene exposure may induce up-regulation of neurotrophin-related gene expression in the mouse hippocampus depending on the mouse strain and an allergic stimulation in sensitive strain may decrease the threshold for sensitivity at lower exposure level.

  16. 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

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

    PubMed

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

    2016-02-09

    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.

  18. 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

  19. Escherichia coli response to uranyl exposure at low pH and associated protein regulations.

    PubMed

    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 coli cells 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 analyzed by 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.

  20. 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.

  1. Up-Regulation of miR-21 Expression Predicate Advanced Clinicopathological Features and Poor Prognosis in Patients with Non-Small Cell Lung Cancer.

    PubMed

    Tian, Lei; Shan, Weiyu; Zhang, Yufei; Zhnag, Yufei; Lv, Xuejun; Li, Xuehua; Wei, Caiyun

    2016-01-01

    MicroRNAs (miRNAs) are endogenous small (19-24 nt long) noncoding RNAs that regulate gene expression in a sequence specific manner. An increasing association between miRNA and cancer has been recently reported. Lung cancer is globally responsible for 1.4 million deaths annually and is the leading cause of cancer-related deaths in both women and men. In this study, we investigated the miR-21 expression in non-small cell lung cancer (NSCLC) to evaluate their value in prognosis of this tumor. Here, we assess miR-21 expression in NSCLC and its clinical significance including survival analysis. The expression of miR-21 in matched normal and tumor tissues of NSCLC was evaluated using a quantitative real-time RT-PCR. A Kaplan-Meier survival curve was generated following a logrank test. It was observed that miR-21 expression was up-regulated in NSCLC tissues compared with noncancerous lung tissues (mean ± SD: 6.7 ± 2.3 vs. 3.7 ± 1.5, P < 0.001). The up-regulation of miR-21 in NSCLC cancer tissues was also significantly correlated with aggressive clinicopathological features. We found that the patients with high miR-21 expression have a higher tumor grade (P = 0.027) and are in higher risk of lymph node metastasis (P = 0.021). Moreover, the results of Kaplan-Meier analyses showed that NSCLC patients with the high miR-21 expression tend to have shorter overall survival and progression free survival (P < 0.001). The multivariate analysis clearly indicated that the high miR-21 expression in biopsy samples may be considered as an independent prognostic factor in NSCLC for decreased survival (RR 3.88; 95%CI, 2.47-6.11). Our data indicate the potential of miR-21 as a novel prognostic biomarker for NSCLC. Large well-designed studies with diverse populations and functional evaluations are warranted to confirm and extend our findings.

  2. Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.

    PubMed

    Zhao, Xiangshan; Mirza, Sameer; Alshareeda, Alaa; Zhang, Ying; Gurumurthy, Channabasavaiah Basavaraju; Bele, Aditya; Kim, Jun Hyun; Mohibi, Shakur; Goswami, Monica; Lele, Subodh M; West, William; Qiu, Fang; Ellis, Ian O; Rakha, Emad A; Green, Andrew R; Band, Hamid; Band, Vimla

    2012-07-01

    Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.

  3. 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

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

    PubMed

    Reichard, John F; Puga, Alvaro

    2010-02-01

    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 to activate oncogene expression or silence tumor suppressor genes, leading to long-term changes in the 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 as areas where consistencies and inconsistencies exist.

  5. 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

  6. Childhood Maltreatment Exposure and Disruptions in Emotion Regulation: A Transdiagnostic Pathway to Adolescent Internalizing and Externalizing Psychopathology.

    PubMed

    Heleniak, Charlotte; Jenness, Jessica L; Stoep, Ann Vander; McCauley, Elizabeth; McLaughlin, Katie A

    2016-06-01

    Child maltreatment is a robust risk factor for internalizing and externalizing psychopathology in children and adolescents. We examined the role of disruptions in emotion regulation processes as a developmental mechanism linking child maltreatment to the onset of multiple forms of psychopathology in adolescents. Specifically, we examined whether child maltreatment was associated with emotional reactivity and maladaptive cognitive and behavioral responses to distress, including rumination and impulsive behaviors, in two separate samples. We additionally investigated whether each of these components of emotion regulation were associated with internalizing and externalizing psychopathology and mediated the association between child maltreatment and psychopathology. Study 1 included a sample of 167 adolescents recruited based on exposure to physical, sexual, or emotional abuse. Study 2 included a sample of 439 adolescents in a community-based cohort study followed prospectively for 5 years. In both samples, child maltreatment was associated with higher levels of internalizing psychopathology, elevated emotional reactivity, and greater habitual engagement in rumination and impulsive responses to distress. In Study 2, emotional reactivity and maladaptive responses to distress mediated the association between child maltreatment and both internalizing and externalizing psychopathology. These findings provide converging evidence for the role of emotion regulation deficits as a transdiagnostic developmental pathway linking child maltreatment with multiple forms of psychopathology.

  7. Childhood Maltreatment Exposure and Disruptions in Emotion Regulation: A Transdiagnostic Pathway to Adolescent Internalizing and Externalizing Psychopathology

    PubMed Central

    Jenness, Jessica L.; Stoep, Ann Vander; McCauley, Elizabeth; McLaughlin, Katie A.

    2016-01-01

    Child maltreatment is a robust risk factor for internalizing and externalizing psychopathology in children and adolescents. We examined the role of disruptions in emotion regulation processes as a developmental mechanism linking child maltreatment to the onset of multiple forms of psychopathology in adolescents. Specifically, we examined whether child maltreatment was associated with emotional reactivity and maladaptive cognitive and behavioral responses to distress, including rumination and impulsive behaviors, in two separate samples. We additionally investigated whether each of these components of emotion regulation were associated with internalizing and externalizing psychopathology and mediated the association between child maltreatment and psychopathology. Study 1 included a sample of 167 adolescents recruited based on exposure to physical, sexual, or emotional abuse. Study 2 included a sample of 439 adolescents in a community-based cohort study followed prospectively for 5 years. In both samples, child maltreatment was associated with higher levels of internalizing psychopathology, elevated emotional reactivity, and greater habitual engagement in rumination and impulsive responses to distress. In Study 2, emotional reactivity and maladaptive responses to distress mediated the association between child maltreatment and both internalizing and externalizing psychopathology. These findings provide converging evidence for the role of emotion regulation deficits as a transdiagnostic developmental pathway linking child maltreatment with multiple forms of psychopathology. PMID:27695145

  8. 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.

  9. Laboratory capacity building for the International Health Regulations (IHR[2005]) in resource-poor countries: the experience of the African Field Epidemiology Network (AFENET).

    PubMed

    Masanza, Monica Musenero; Nqobile, Ndlovu; Mukanga, David; Gitta, Sheba Nakacubo

    2010-12-03

    Laboratory is one of the core capacities that countries must develop for the implementation of the International Health Regulations (IHR[2005]) since laboratory services play a major role in all the key processes of detection, assessment, response, notification, and monitoring of events. While developed countries easily adapt their well-organized routine laboratory services, resource-limited countries need considerable capacity building as many gaps still exist. In this paper, we discuss some of the efforts made by the African Field Epidemiology Network (AFENET) in supporting laboratory capacity development in the Africa region. The efforts range from promoting graduate level training programs to building advanced technical, managerial and leadership skills to in-service short course training for peripheral laboratory staff. A number of specific projects focus on external quality assurance, basic laboratory information systems, strengthening laboratory management towards accreditation, equipment calibration, harmonization of training materials, networking and provision of pre-packaged laboratory kits to support outbreak investigation. Available evidence indicates a positive effect of these efforts on laboratory capacity in the region. However, many opportunities exist, especially to support the roll-out of these projects as well as attending to some additional critical areas such as biosafety and biosecuity. We conclude that AFENET's approach of strengthening national and sub-national systems provide a model that could be adopted in resource-limited settings such as sub-Saharan Africa.

  10. High expression of glucose-regulated protein 78 (GRP78) is associated with metastasis and poor prognosis in patients with esophageal squamous cell carcinoma

    PubMed Central

    Ren, Peng; Chen, Chuangui; Yue, Jie; Zhang, Jianguo; Yu, Zhentao

    2017-01-01

    Background Glucose-regulated protein 78 (GRP78) plays an important role in the invasion and metastasis of many human cancers. However, the role of this protein in the progression of invasion and metastasis in esophageal squamous cell carcinoma (ESCC) remains elusive. Patients and methods Immunohistochemistry and Western blot were performed to analyze GRP78 expression in 92 patients with primary ESCC. The correlation of GRP78 expression with clinicopathological factors was analyzed. In vitro, the expression levels of GRP78 were downregulated by small interfering RNA transfection in TE-1 and CaEs-17 ESCC lines. Cell invasion and migration assays were applied to determine the invasion and migratory abilities of ESCC cells. Results Compared with GRP78 in adjacent normal esophageal tissues, GRP78 was overexpressed in ESCC tissues. High GRP78 expression was significantly correlated with positive lymph node metastasis (P=0.035) and advanced tumor stage (P=0.017). Survival analysis revealed that high GRP78 expression was significantly associated with shorter overall survival (P=0.037). In multivariate analysis, GRP78 overexpression was identified as an independent prognostic factor for overall survival (P=0.011). si-GRP78 can significantly decrease the GRP78 expression level and reverse the invasion and migratory abilities of ESCC cells in TE-1 and CaEs-17 cell lines. Conclusion These findings demonstrated that high expression of GRP78 was associated with disease progression and metastasis in ESCC and might serve as a novel prognostic marker for patients with ESCC. PMID:28228658

  11. Role of zinc in the regulation of autophagy during ethanol exposure in human hepatoma cells.

    PubMed

    Liuzzi, J P; Yoo, Chanwong

    2013-12-01

    Faulty autophagy has been linked to various diseases including neurodegenerative disorders, diabetes, and cancer. Increasing evidence support the notion that activation of autophagy protects against ethanol-induced steatosis and liver injury. Herein, we investigated the role of zinc in autophagy in human hepatoma cells VL-17A exposed or not to ethanol. LC3II/LC3I ratio, p62, and Beclin-1 expression and autophagosomes number were determined in cells incubated in medium containing various concentrations of zinc with or without ethanol. In addition, labile zinc and mRNA expression of metallothionein and the zinc transporters SLC39A8, SLC39A14, and SLC30A10 were evaluated in cells exposed to ethanol and the autophagy inhibitor 3-methyladenine. Zinc depletion caused a significant suppression of autophagy in cells. Conversely, zinc addition to medium stimulated autophagy in cells. Moreover, cotreatment with ethanol and excess zinc (40 μM) had an additive effect on the induction of autophagy. 3-methyadenine treatment decreased labile zinc, but this effect was more pronounced in cells exposed to ethanol. Lastly, ethanol and 3-methyladenine caused significant changes in the expression of metallothionein and zinc transporters. The results from this study support the hypothesis that zinc is critical for autophagy under basal conditions and during ethanol exposure.

  12. Up-regulation of reactivity and survival genes in astrocytes after exposure to short duration overpressure.

    PubMed

    Vandevord, Pamela J; Leung, Lai Yee; Hardy, Warren; Mason, Matthew; Yang, King H; King, Albert I

    2008-04-04

    Gurdjian et al. proposed decades ago that pressure gradients played a major factor in neuronal injury due to impact. In the late 1950s, their experiments on concussion demonstrated that the principal factor in the production of concussion in animals was the sudden increase of intracranial pressure accompanying head injury. They reported the increase in pressure severity correlated with an increase in 'altered cells' resulting in animal death. More recently, Hardy et al. (2006) demonstrated the presence of transient pressure pulses with impact conditions. These studies indicate that short duration overpressure should be further examined as a mechanism of traumatic brain injury (TBI). In the present study, we designed and fabricated a barochamber that simulated overpressure noted in various head injury studies. We tested the effect of overpressure on astrocytes. Expressions of apoptotic, reactivity and survival genes were examined at 24, 48 and 72 h post-overpressure exposure. At 24 h, we found elevated levels of reactivity and survival gene expression. By 48 h, a decreased expression of apoptotic genes was demonstrated. This study reinforces the hypothesis that transient pressure acts to instigate the cellular response displayed following TBI.

  13. 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.

  14. Regulation of apoptosis by vitamin C. Specific protection of the apoptotic machinery against exposure to chlorinated oxidants.

    PubMed

    Vissers, M C; Lee, W G; Hampton, M B

    2001-12-14

    We have investigated the ability of intracellular vitamin C to protect human umbilical vein endothelial cells from exposure to hypochlorous acid (HOCl) and a range of derived chloramines. Ascorbate provided minimal protection against the cytotoxicity induced by these oxidants, as measured by propidium iodide uptake. In contrast, there was a marked effect on apoptosis, monitored by caspase-3 activation and phosphatidylserine exposure. Extended incubation of the cells with glycine chloramine or histamine chloramine completely blocked apoptosis initiated in the cells by serum withdrawal. This effect was significantly abrogated by ascorbate. Inhibition of apoptosis required the oxidant to be present for an extended period after serum withdrawal and occurred prior to caspase-3 activation. General protection of thiols by ascorbate was not responsible for the protection of apoptosis, because intracellular oxidation by HOCl or chloramines was not prevented in supplemented cells. The results suggest a new role for vitamin C in the regulation of apoptosis. We propose that, by protection of an oxidant-sensitive step in the initiation phase, ascorbate allows apoptosis to proceed in endothelial cells under sustained oxidative stress.

  15. 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

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

    PubMed Central

    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.

    2015-01-01

    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 (10nM, 200nM, and 1000nM) or estradiol-17β (E2) (0.1nM) 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

  17. 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

  18. 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

  19. 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…

  20. 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.

  1. 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.

  2. Single dose exposure of sarin and physostigmine differentially regulates expression of choline acetyltransferase and vesicular acetylcholine transporter in rat brain.

    PubMed

    Bhardwaj, Sonika; Musalgaonkar, Nidhi; Waghmare, Chandrakant; Bhattacharya, Bijoy K

    2012-06-25

    Choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) are the key components of cholinergic system apart from acetylcholinesterase. Effects of subcutaneous exposures of 0.25 and 0.5 LD(50) sarin and 0.75 mg/kg physostigmine on immunoreactivity levels of these two proteins (ChAT and VAChT) were studied. Immunoreactivity levels of ChAT decreased significantly after 1 and 3 days in cortex and 3 days of 0.25 LD(50) sarin administration in cerebellum. While 0.5 LD(50) sarin exposure caused significant down regulation after 2.5 h to 7 days in cortex and 1 and 3 days in cerebellum with respect to controls. Physostigmine at 0.75 mg/kg dose showed enhanced levels of ChAT after 1 day which decreased significantly after 3 and 7 days both in cortex and cerebellum compared to controls. VAChT level decreased significantly after 1 day in cortex and 3 and 7 days in cerebellum after 0.25 LD(50) sarin administration, while 0.5 LD(50) sarin significantly lowered VAChT immunoreactivity level after 2.5 h and 7 days in cortex and 2.5 h and 1 day in cerebellum. Physostigmine at 0.75 mg/kg dose showed significant enhanced immunoreactivity levels of VAChT after 1, 3, and 7 days in cortex and 3 days in cerebellum. Results show that acetylcholinesterase inhibition by sarin caused reduction in cholinergic neurotransmission at cholinergic proteins expression levels, while physostigmine caused differential expression of key cholinergic proteins. Moreover, cortex, which receives greater cholinergic innervations, is more susceptible to anticholinesterase effect on cholinergic gene expression. These changes can explain delayed neurocognitive changes during anticholinesterases induced chronic neurotoxicity.

  3. 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)...

  4. The effectiveness of tobacco marketing regulations on reducing smokers' exposure to advertising and promotion: findings from the International Tobacco Control (ITC) Four Country Survey.

    PubMed

    Kasza, Karin A; Hyland, Andrew J; Brown, Abraham; Siahpush, Mohammad; Yong, Hua-Hie; McNeill, Ann D; Li, Lin; Cummings, K Michael

    2011-02-01

    Exposure to tobacco product marketing promotes the initiation, continuation, and reuptake of cigarette smoking and as a result the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) has called upon member Parties to enact comprehensive bans on tobacco advertising and promotion. This study examines the immediate and long term effectiveness of advertising restrictions enacted in different countries on exposure to different forms of product marketing, and examines differences in exposure across different socioeconomic status (SES) groups. Nationally representative data from the United Kingdom, Canada, Australia, and the United States, collected from adult smokers between 2002 and 2008 using the International Tobacco Control Four Country Survey (ITC-4), were used in this study (N = 21,615). In light of the specific marketing regulation changes that occurred during the course of this study period, changes in awareness of tobacco marketing via various channels were assessed for each country, and for different SES groups within countries. Tobacco marketing regulations, once implemented, were associated with significant reductions in smokers' reported awareness of pro-smoking cues, and the observed reductions were greatest immediately following the enactment of regulations. Changes in reported awareness were generally the same across different SES groups, although some exceptions were noted. While tobacco marketing regulations have been effective in reducing exposure to certain types of product marketing there still remain gaps, especially with regard to in-store marketing and price promotions.

  5. 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

  6. Endogenous nitric oxide regulates the recovery of the radiation-resistant bacterium Deinococcus radiodurans from exposure to UV light

    PubMed Central

    Patel, Bhumit A.; Moreau, Magali; Widom, Joanne; Chen, Huan; Yin, Longfei; Hua, Yuejin; Crane, Brian R.

    2009-01-01

    Deinococcus radiodurans (Dr) withstands desiccation, reactive oxygen species, and doses of radiation that would be lethal to most organisms. Deletion of a gene encoding a homolog of mammalian nitric oxide synthase (NOS) severely compromises the recovery of Dr from ultraviolet (UV) radiation damage. The Δnos defect can be complemented with recombinant NOS, rescued by exogenous nitric oxide (NO) and mimicked in the wild-type strain with an NO scavenging compound. UV radiation induces both upregulation of the nos gene and cellular NO production on similar time scales. Growth recovery does not depend on NO being present during UV irradiation, but rather can be manifested by NO addition hours after exposure. Surprisingly, nos deletion does not increase sensitivity to oxidative damage, and hydrogen peroxide does not induce nos expression. However, NOS-derived NO upregulates transcription of obgE, a gene involved in bacterial growth proliferation and stress response. Overexpression of the ObgE GTPase in the Δnos background substantially alleviates the growth defect after radiation damage. Thus, NO acts as a signal for the transcriptional regulation of growth in D. radiodurans. PMID:19841256

  7. Application of Acute Maximal Exercise to Enhance Mechanisms Underlying Blood Pressure Regulation and Orthostatic Tolerance After Exposure to Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Engelke, K. A.; Doerr, D. F.

    1999-01-01

    Development of orthostatic hypotension and intolerance in astronauts who return to earth following a spaceflight mission represents a significant operational concern to NASA. Reduced plasma volume, vascular resistance, and baroreflex responsiveness following exposure to actual and ground-based analogs of microgravity have been associated with orthostatic instability, suggesting that these mechanisms may contribute alone or in combination to compromise of blood pressure regulation after spaceflight. It therefore seems reasonable that development of procedures designed to reverse or restore the effects of microgravity on regulatory mechanisms of blood volume, vascular resistance and cardiac function should provide some protection against postflight orthostatic intolerance. Several investigations have provided evidence that a single bout of exhaustive dynamic exercise enhances functions of mechanisms responsible for blood pressure stability. Therefore, the purpose of our research project was to conduct a series of experiments using ground-based analogs of reduced gravity (i.e., prolonged restriction to the upright standing posture) in human subjects to investigate the hypothesis that a single bout of dynamic maximal exercise would restore blood volume, vascular resistance and cardiac function and improve blood pressure stability.

  8. Volume regulation in mammalian skeletal muscle: the role of sodium–potassium–chloride cotransporters during exposure to hypertonic solutions

    PubMed Central

    Lindinger, Michael I; Leung, Matthew; Trajcevski, Karin E; Hawke, Thomas J

    2011-01-01

    Abstract Controversy exists as to whether mammalian skeletal muscle is capable of volume regulation in response to changes in extracellular osmolarity despite evidence that muscle fibres have the required ion transport mechanisms to transport solute and water in situ. We addressed this issue by studying the ability of skeletal muscle to regulate volume during periods of induced hyperosmotic stress using single, mouse extensor digitorum longus (EDL) muscle fibres and intact muscle (soleus and EDL). Fibres and intact muscles were loaded with the fluorophore, calcein, and the change in muscle fluorescence and width (single fibres only) used as a metric of volume change. We hypothesized that skeletal muscle exposed to increased extracellular osmolarity would elicit initial cellular shrinkage followed by a regulatory volume increase (RVI) with the RVI dependent on the sodium–potassium–chloride cotransporter (NKCC). We found that single fibres exposed to a 35% increase in extracellular osmolarity demonstrated a rapid, initial 27–32% decrease in cell volume followed by a RVI which took 10–20 min and returned cell volume to 90–110% of pre-stimulus values. Within intact muscle, exposure to increased extracellular osmolarity of varying degrees also induced a rapid, initial shrinkage followed by a gradual RVI, with a greater rate of initial cell shrinkage and a longer time for RVI to occur with increasing extracellular tonicities. Furthermore, RVI was significantly faster in slow-twitch soleus than fast-twitch EDL. Pre-treatment of muscle with bumetanide (NKCC inhibitor) or ouabain (Na+,K+-ATPase inhibitor), increased the initial volume loss and impaired the RVI response to increased extracellular osmolarity indicating that the NKCC is a primary contributor to volume regulation in skeletal muscle. It is concluded that mouse skeletal muscle initially loses volume then exhibits a RVI when exposed to increases in extracellular osmolarity. The rate of RVI is dependent

  9. Volume regulation in mammalian skeletal muscle: the role of sodium-potassium-chloride cotransporters during exposure to hypertonic solutions.

    PubMed

    Lindinger, Michael I; Leung, Matthew; Trajcevski, Karin E; Hawke, Thomas J

    2011-06-01

    Controversy exists as to whether mammalian skeletal muscle is capable of volume regulation in response to changes in extracellular osmolarity despite evidence that muscle fibres have the required ion transport mechanisms to transport solute and water in situ. We addressed this issue by studying the ability of skeletal muscle to regulate volume during periods of induced hyperosmotic stress using single, mouse extensor digitorum longus (EDL) muscle fibres and intact muscle (soleus and EDL). Fibres and intact muscles were loaded with the fluorophore, calcein, and the change in muscle fluorescence and width (single fibres only) used as a metric of volume change. We hypothesized that skeletal muscle exposed to increased extracellular osmolarity would elicit initial cellular shrinkage followed by a regulatory volume increase (RVI) with the RVI dependent on the sodium–potassium–chloride cotransporter (NKCC). We found that single fibres exposed to a 35% increase in extracellular osmolarity demonstrated a rapid, initial 27–32% decrease in cell volume followed by a RVI which took 10-20 min and returned cell volume to 90–110% of pre-stimulus values. Within intact muscle, exposure to increased extracellular osmolarity of varying degrees also induced a rapid, initial shrinkage followed by a gradual RVI, with a greater rate of initial cell shrinkage and a longer time for RVI to occur with increasing extracellular tonicities. Furthermore, RVI was significantly faster in slow-twitch soleus than fast-twitch EDL. Pre-treatment of muscle with bumetanide (NKCC inhibitor) or ouabain (Na+,K+-ATPase inhibitor), increased the initial volume loss and impaired the RVI response to increased extracellular osmolarity indicating that the NKCC is a primary contributor to volume regulation in skeletal muscle. It is concluded that mouse skeletal muscle initially loses volume then exhibits a RVI when exposed to increases in extracellular osmolarity. The rate of RVI is dependent on the

  10. Copper exposure interferes with the regulation of the uptake, distribution and metabolism of sulfate in Chinese cabbage.

    PubMed

    Shahbaz, Muhammad; Tseng, Mei Hwei; Stuiver, C Elisabeth E; Koralewska, Aleksandra; Posthumus, Freek S; Venema, Jan Henk; Parmar, Saroj; Schat, Henk; Hawkesford, Malcolm J; De Kok, Luit J

    2010-04-15

    Exposure of Chinese cabbage (Brassica pekinensis) to enhanced Cu(2+) concentrations (1-10 microM) resulted in leaf chlorosis, a loss of photosynthetic capacity and lower biomass production at > or = 5 microM. The decrease in pigment content was likely not the consequence of degradation, but due to hindered chloroplast development upon Cu exposure. The Cu content of the root increased with the Cu(2+) concentration (up to 40-fold), though only a minor proportion (4%) was transferred to the shoot. The nitrate uptake by the root was substantially reduced at > or = 5 microM Cu(2+). The nitrogen content of the root was affected little at lower Cu(2+) levels, whereas that in the shoot was decreased at > or = 5 microM Cu(2+). Cu affected the uptake, distribution and metabolism of sulfate in Chinese cabbage. The total sulfur content of the shoot was increased at > or = 2 microM Cu(2+), which could be attributed mainly to an increase in sulfate content. Moreover, there was a strong increase in water-soluble non-protein thiol content in the root and, to a lesser extent, in the shoot at > or = 1 microM, which could only partially be ascribed to a Cu-induced enhancement of the phytochelatin content. The nitrate uptake by the root was substantially reduced at > or = 5 microM Cu(2+), coinciding with a decrease in biomass production. However, the activity of the sulfate transporters in the root was slightly enhanced at 2 and 5 microM Cu(2+), accompanied by enhanced expression of the Group 1 high affinity transporter Sultr1;2, and the Group 4 transporters Sultr4;1 and Sultr4;2. In the shoot, there was an induction of expression of Sultr4;2 at 5 and 10 microM Cu(2+). The expression of APS reductase was affected little in the root and shoot up to 10 microM Cu(2+). The upregulation of the sulfate transporters may be due not only to greater sulfur demand at higher Cu levels, but also the consequence of interference by Cu with the signal transduction pathway regulating the expression

  11. Down regulation of RNA binding motif, single-stranded interacting protein 3, along with up regulation of nuclear HIF1A correlates with poor prognosis in patients with gastric cancer.

    PubMed

    Wu, Youliang; Yun, Dapeng; Zhao, Yingjie; Wang, Yuqi; Sun, Ruochuan; Yan, Qiang; Zhang, Shangxin; Lu, Mingdian; Zhang, Zhen; Lu, Daru; Li, Yongxiang

    2017-01-03

    Frequent loss of multiple regions in short arm of chromosome 3 is found in various tumors including gastric cancer (GC). RNA binding motif, single-stranded interacting protein 3 (RBMS3) is a tumor suppressor gene located in this region and mediates cancer angiogenesis. However, the role of RBMS3 in GC remains unclear.To evaluate whether RBMS3, together with HIF1A, another key regulator of angiogenesis, predicts GC prognosis, the levels of RBMS3 and HIF1A were first examined by quantitative PCR (qPCR) and western blot from 27 fresh frozen GC and paired normal gastric tissues and then tested by immunohistochemistry (IHC) from 191 GC and 46 normal controls. Moreover, uni- and multivariate analysis were employed to assess the correlations between their levels and microvessel density (MVD) and clinical prognosis. To further identify RBMS3 function in vitro, cell proliferation assay, clonogenic assay, flow cytometry analysis and endothelial cell tube formation assay were employed.We found that RBMS3 level was decreased, whereas HIF1A was elevated in GC. Furthermore, we demonstrated that RBMS3 was an independent prognostic factor and the levels of RBMS3 and HIF1A were associated with GC angiogenesis and histopathological differentiation: patients with lower RBMS3 level and higher nuclear HIF1A expression had poorer prognosis. Besides, gain- and loss-of-function study revealed RBMS3 regulation on G1/S progression, cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. These findings implicated that RBMS3 and nuclear HIF1A could act as prognostic biomarkers and therapeutic targets for GC.

  12. Down regulation of RNA binding motif, single-stranded interacting protein 3, along with up regulation of nuclear HIF1A correlates with poor prognosis in patients with gastric cancer

    PubMed Central

    Zhao, Yingjie; Wang, Yuqi; Sun, Ruochuan; Yan, Qiang; Zhang, Shangxin; Lu, Mingdian; Zhang, Zhen; Lu, Daru; Li, Yongxiang

    2017-01-01

    Frequent loss of multiple regions in short arm of chromosome 3 is found in various tumors including gastric cancer (GC). RNA binding motif, single-stranded interacting protein 3 (RBMS3) is a tumor suppressor gene located in this region and mediates cancer angiogenesis. However, the role of RBMS3 in GC remains unclear. To evaluate whether RBMS3, together with HIF1A, another key regulator of angiogenesis, predicts GC prognosis, the levels of RBMS3 and HIF1A were first examined by quantitative PCR (qPCR) and western blot from 27 fresh frozen GC and paired normal gastric tissues and then tested by immunohistochemistry (IHC) from 191 GC and 46 normal controls. Moreover, uni- and multivariate analysis were employed to assess the correlations between their levels and microvessel density (MVD) and clinical prognosis. To further identify RBMS3 function in vitro, cell proliferation assay, clonogenic assay, flow cytometry analysis and endothelial cell tube formation assay were employed. We found that RBMS3 level was decreased, whereas HIF1A was elevated in GC. Furthermore, we demonstrated that RBMS3 was an independent prognostic factor and the levels of RBMS3 and HIF1A were associated with GC angiogenesis and histopathological differentiation: patients with lower RBMS3 level and higher nuclear HIF1A expression had poorer prognosis. Besides, gain- and loss-of-function study revealed RBMS3 regulation on G1/S progression, cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. These findings implicated that RBMS3 and nuclear HIF1A could act as prognostic biomarkers and therapeutic targets for GC. PMID:27902480

  13. Low-dose exposure to bisphenol A in combination with fructose increases expression of genes regulating angiogenesis and vascular tone in juvenile Fischer 344 rat cardiac tissue

    PubMed Central

    Klint, Helén; Karimullina, Elina; Rönn, Monika; Lind, Lars; Lind, P. Monica

    2017-01-01

    Objectives Epidemiological studies report associations between exposure to the high-volume chemical and endocrine disruptor bisphenol A (BPA) and cardiovascular disorders, but there is a lack of experimental studies addressing the mechanisms of action of BPA on the cardiovascular system. In the present study, effects on markers for cardiovascular function of exposure to BPA and fructose in vivo in rat cardiac tissues, and of BPA exposure in human cardiomyocytes in vitro, were investigated. Materials Juvenile female Fischer 344 rats were exposed to 5, 50, and 500 μg BPA/kg bodyweight/day in their drinking water from 5 to 15 weeks of age, in combination with 5% fructose. Further, cultured human cardiomyocytes were exposed to 10 nM BPA to 1 × 104 nM BPA for six hours. Expression of markers for cardiovascular function and BPA target receptors was investigated using qRT-PCR. Results Exposure to 5 μg BPA/kg bodyweight/day plus fructose increased mRNA expression of Vegf, Vegfr2, eNos, and Ace1 in rat heart. Exposure of human cardiomyocytes to 1 × 104 nM BPA increased mRNA expression of eNOS and ACE1, as well as IL-8 and NFκβ known to regulate inflammatory response. Conclusions:. Low-dose exposure of juvenile rats to BPA and fructose induced up-regulation of expression of genes controlling angiogenesis and vascular tone in cardiac tissues. The observed effects of BPA in rat heart were in line with our present and previous studies of BPA in human endothelial cells and cardiomyocytes. These findings may aid in understanding the mechanisms of the association between BPA exposure and cardiovascular disorders reported in epidemiological studies. PMID:27622962

  14. 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

  15. 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.

  16. The Poor Pay More.

    ERIC Educational Resources Information Center

    Folse, Kimberly A.

    2002-01-01

    Describes a sociology experiential learning assignment where students learned why people living in poverty can sometimes pay more for products than people with better incomes. Focuses specifically on the rent to own concept. States students achieved the goal of learning how life constraints of poverty can hinder the poor from overcoming their…

  17. Confronting Poor Performance.

    ERIC Educational Resources Information Center

    Dennis, Bruce L.

    Responsible and effective administrative leadership requires confronting those members of the teaching staff who are a negative influence on the institution. Importantly, the absence of expressed appreciation for good work can have a devastating impact on a principal's image if he or she suddenly begins to confront poor performances. Actually, the…

  18. Letting the poor speak.

    PubMed

    2000-09-29

    This paper comments on two documents prepared by the Washington-based World Bank: the "World Development Report" and the three-volume study "Voices of the Poor." The author provides a brief overview of these documents then examines their potential impact on the delegates to the annual meetings of the World Bank and the International Monetary Fund in Prague on September 19-28, 2000. The author further examines the implication of the new strategies embraced by the global lenders--"opportunity, empowerment, security." Apart from these strategies, the World Bank sets out other strategies like spreading the benefits of technology, as it calls for the elimination of absolute poverty by 2015. However, the most crucial tack is the one illustrated by the way the reports were made: letting the poor speak and responding to their cries.

  19. Prolonged nicotine exposure down-regulates presynaptic NMDA receptors in dopaminergic terminals of the rat nucleus accumbens.

    PubMed

    Salamone, Alessia; Zappettini, Stefania; Grilli, Massimo; Olivero, Guendalina; Agostinho, Paula; Tomé, Angelo R; Chen, Jiayang; Pittaluga, Anna; Cunha, Rodrigo A; Marchi, Mario

    2014-04-01

    The presynaptic control of dopamine release in the nucleus accumbens (NAc) by glutamate and acetylcholine has a profound impact on reward signaling. Here we provide immunocytochemical and neurochemical evidence supporting the co-localization and functional interaction between nicotinic acetylcholine receptors (nAChRs) and N-methyl-D-aspartic acid (NMDA) receptors in dopaminergic terminals of the NAc. Most NAc dopaminergic terminals possessed the nAChR α4 subunit and the pre-exposure of synaptosomes to nicotine (30 μM) or to the α4β2-containing nAChR agonist 5IA85380 (10 nM) selectively inhibited the NMDA (100 μM)-evoked, but not the 4-aminopyridine (10 μM)-evoked, [(3)H] dopamine outflow; this inhibition was blunted by mecamylamine (10 μM). Nicotine and 5IA85380 pretreatment also inhibited the NMDA (100 μM)-evoked increase of calcium levels in single nerve terminals, an effect prevented by dihydro-β-erythroidine (1 μM). This supports a functional interaction between α4β2-containing nAChR and NMDA receptors within the same terminal, as supported by the immunocytochemical co-localization of α4 and GluN1 subunits in individual NAc dopaminergic terminals. The NMDA-evoked [(3)H]dopamine outflow was blocked by MK801 (1 μM) and inhibited by the selective GluN2B-selective antagonists ifenprodil (1 μM) and RO 25-6981 (1 μM), but not by the GluN2A-preferring antagonists CPP-19755 (1 μM) and ZnCl2 (1 nM). Notably, nicotine pretreatment significantly decreased the density of biotin-tagged GluN2B proteins in NAc synaptosomes. These results show that nAChRs dynamically and negatively regulate NMDA receptors in NAc dopaminergic terminals through the internalization of GluN2B receptors.

  20. Yokukansan normalizes glucocorticoid receptor protein expression in oligodendrocytes of the corpus callosum by regulating microRNA-124a expression after stress exposure.

    PubMed

    Shimizu, Shoko; Tanaka, Takashi; Tohyama, Masaya; Miyata, Shingo

    2015-05-01

    Stressful events are known to down-regulate expression levels of glucocorticoid receptors (GRs) in the brain. Recently, we reported that stressed mice with elevated plasma levels of corticosterone exhibit morphological changes in the oligodendrocytes of nerve fiber bundles, such as those in the corpus callosum. However, little is known about the molecular mechanism of GR expression regulation in oligodendrocytes after stress exposure. A previous report has suggested that GR protein levels might be regulated by microRNA (miR)-18 and/or -124a in the brain. In this study, we aimed to elucidate the GR regulation mechanism in oligodendrocytes and evaluate the effects of yokukansan (YKS), a Kampo medicine, on GR protein regulation. Acute exposure to stress increased plasma corticosterone levels, decreased GR protein expression, and increased miR-124a expression in the corpus callosum of adult male mice, though the GR mRNA and miR-18 expression levels were not significant changes. YKS normalized the stress-induced changes in the plasma corticosterone, GR protein, and miR124a expression levels. An oligodendrocyte primary culture study also showed that YKS down-regulated miR-124a, but not miR-18, expression levels in dexamethasone-treated cells. These results suggest that the down-regulation of miR124a expression might be involved in the normalization of stress-induced decreases in GR protein in oligodendrocytes by YKS. This effect may imply the molecular mechanisms underlying the ameliorative effects of YKS on psychological symptoms and stress-related behaviors.

  1. 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

  2. Regulation of morphological, molecular and nutrient status in Arabidopsis thaliana seedlings in response to ZnO nanoparticles and Zn ion exposure.

    PubMed

    Nair, Prakash M Gopalakrishnan; Chung, Ill Min

    2017-01-01

    This study examined the mechanism of toxicity in Arabidopsis thaliana seedlings to zinc oxide nanoparticles (ZnO NPs) and zinc (Zn) ions. We subjected plants to different ZnO NPs and Zn ion concentrations (0, 20, 50, 100 and 200mg/L) and analyzed resulting morphological changes, transcriptional regulation of genes involved in Zn-homeostasis, macro- and microelement homeostasis, as well as auxin regulation. Except for 20mg/L, the fresh weight and primary root length was reduced after exposure to all other concentrations of Zn ion and ZnO NP concentrations. An increase in lateral root formation (19 and 32%) was observed after exposure to 20 and 50mg/L of Zn ions respectively; whereas 20mg/L ZnO NPs treatment triggered a 9% increase in lateral root formation. Both qualitative, using Zynpyr-1 fluorescent probe and quantitative analysis revealed Zn uptake and translocation from roots to shoots after Zn ion exposure. However, ZnO NPs-treated seedlings resulted in no root to shoot translocation and Zn accumulation was mainly located in root tips, primary-lateral root junctions and root- shoot junctions. The macronutrients viz. P (1.34mg/kg DW), K (13.29mg/kg DW), S (1.29mg/kg DW) and micronutrients Cu (0.004mg/kg DW) and Fe (0.345mg/kg DW) contents were highly decreased as a result of exposure to 200mg/L of Zn ions. Similarly, the highest reduction of P (2.30mg/kg DW), K (6.36mg/kg DW), S (2.63mg/kg DW) and Cu (0.004mg/kg DW) was observed after exposure to 200mg/L of ZnO NPs. Gene regulation studies indicated the transcriptional modulation of various genes involved in Zn, macro- and micro nutrient homeostasis as well as hormone regulation. Taken together, it was observed that the mechanism of toxicity of Zn ions and ZnO NPs were different. These findings will help to design safer strategies for the application of ZnO NPs as plant fertilizer without compromising the morphological and nutritional qualities as well as for the future phytoremediation purposes.

  3. Repeated Exposure to D-Amphetamine Decreases Global Protein Synthesis and Regulates the Translation of a Subset of mRNAs in the Striatum

    PubMed Central

    Biever, Anne; Boubaker-Vitre, Jihane; Cutando, Laura; Gracia-Rubio, Irene; Costa-Mattioli, Mauro; Puighermanal, Emma; Valjent, Emmanuel

    2017-01-01

    Repeated psychostimulant exposure induces persistent gene expression modifications that contribute to enduring changes in striatal GABAergic spiny projecting neurons (SPNs). However, it remains unclear whether changes in the control of mRNA translation are required for the establishment of these durable modifications. Here we report that repeated exposure to D-amphetamine decreases global striatal mRNA translation. This effect is paralleled by an enhanced phosphorylation of the translation factors, eIF2α and eEF2, and by the concomitant increased translation of a subset of mRNAs, among which the mRNA encoding for the activity regulated cytoskeleton-associated protein, also known as activity regulated gene 3.1 (Arc/Arg3.1). The enrichment of Arc/Arg3.1 mRNA in the polysomal fraction is accompanied by a robust increase of Arc/Arg3.1 protein levels within the striatum. Immunofluorescence analysis revealed that this increase occurred preferentially in D1R-expressing SPNs localized in striosome compartments. Our results suggest that the decreased global protein synthesis following repeated exposure to D-amphetamine favors the translation of a specific subset of mRNAs in the striatum. PMID:28119566

  4. 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

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

    PubMed

    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.

  6. Differential modulation of ammonia excretion, Rhesus glycoproteins and ion-regulation in common carp (Cyprinus carpio) following individual and combined exposure to waterborne copper and ammonia.

    PubMed

    Sinha, Amit Kumar; Kapotwe, Mumba; Dabi, Shambel Boki; Montes, Caroline da Silva; Shrivastava, Jyotsna; Blust, Ronny; De Boeck, Gudrun

    2016-01-01

    The main objective of this study was to understand the mode of interaction between waterborne copper (Cu) and high environmental ammonia (HEA) exposure on freshwater fish, and how they influence the toxicity of each other when present together. For this purpose, individual and combined effects of Cu and HEA were examined on selected physiological and ion-regulatory processes and changes at transcript level in the common carp (Cyprinus carpio). Juvenile carp were exposed to 2.6μM Cu (25% of the 96h LC50value) and to 0.65mM ammonia (25% of the 96h LC50value) singly and as a mixture for 12h, 24h, 48h, 84h and 180h. Responses such as ammonia (Jamm) and urea (Jurea) excretion rate, plasma ammonia and urea, plasma ions (Na(+), Cl(-) and K(+)), muscle water content (MWC) as well as branchial Na(+)/K(+)-ATPase (NKA) and H(+)-ATPase activity, and branchial mRNA expression of NKA, H(+)-ATPase, Na(+)/H(+) exchanger (NHE-3) and Rhesus (Rh) glycoproteins were investigated under experimental conditions. Results show that Jamm was inhibited during Cu exposure, while HEA exposed fish were able to increase excretion efficiently. In the combined exposure, Jamm remained at the control levels indicating that Cu and HEA abolished each other's effect. Expression of Rhcg (Rhcg-a and Rhcg-b) mRNA was upregulated during HEA, thereby facilitated ammonia efflux out of gills. On the contrary, Rhcg-a transcript level declined following Cu exposure which might account for Cu induced Jamm inhibition. Likewise, Rhcg-a was also down-regulated in Cu-HEA co-exposed fish whilst a temporary increment was noted for Rhch-b. Fish exposed to HEA displayed pronounced up-regulation in NKA expression and activity and stable plasma ion levels. In both the Cu exposure alone and combined Cu-HEA exposure, ion-osmo homeostasis was adversely affected, exemplified by the significant reduction in plasma [Na(+)] and [Cl(-)], and elevated plasma [K(+)], along with an elevation in MWC. These changes were accompanied

  7. 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

  8. A late IL-33 response after exposure to Schistosoma haematobium antigen is associated with an up-regulation of IL-13 in human eosinophils

    PubMed Central

    Wilson, S; Jones, F M; Fofana, H K M; Landouré, A; Kimani, G; Mwatha, J K; Sacko, M; Vennervald, B J; Dunne, D W

    2013-01-01

    IL-33, a proposed alarmin, stimulates innate immune cells and Th2 cells to produce IL-13 and is rapidly upregulated upon antigen exposure in murine helminth infection. The human IL-33 response to helminth antigen was analysed in Malians infected with Schistosoma haematobium by disrupting parasite integrity via chemotherapy. Plasma IL-33 was measured pretreatment, and 24 h and 9 weeks post-treatment. At 24 h post-treatment, IL-33 levels were low. Nine week post-treatment IL-33 levels were elevated and were associated with an increase in intracellular IL-13 in eosinophils. Up-regulation of intracellular IL-13 in eosinophils was also associated with eosinophil expression of ST2L, the IL-33 receptor. IL-33 may play an important downstream role in the human response to schistosome adult worm antigen exposure. PMID:23521712

  9. 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

  10. Gestational lead exposure induces developmental abnormalities and up-regulates apoptosis of fetal cerebellar cells in rats.

    PubMed

    Mousa, Alyaa M; Al-Fadhli, Ameera S; Rao, Muddanna S; Kilarkaje, Narayana

    2015-01-01

    Lead (Pb), a known environmental toxicant, adversely affects almost all organ systems. In this study, we investigated the effects of maternal lead exposure on fetal rat cerebellum. Female Sprague-Dawley rats were given lead nitrate in drinking water (0, 0.5, and 1%) for two weeks before conception, and during pregnancy. Fetuses were collected by caesarian section on gestational day 21 and observed for developmental abnormalities. The fetal cerebellar sections from control and 1% lead group were stained with cresyl violet. Immunohistochemical expressions of p53, Bax, Bcl-2, and caspase 3 were quantified by AnalySIS image analyzer (Life Science, Germany). Lead exposure induced developmental abnormalities of eyes, ear, limbs, neck and ventral abdominal wall; however, these abnormalities were commonly seen in the 1% lead-treated group. In addition, lead also caused fetal mortality and reduced body growth in both dose groups and reduced brain weight in the 1% lead-treated group. The fetal cerebella from the 1% lead-treated group showed unorganized cerebellar cortical layers, and degenerative changes in granule and Purkinje cells such as the formation of clumps of Nissl granules. An increase in Bax and caspase 3, and a decrease in Bcl-2 (p < 0.05), but not in p53, showed apoptosis of the neurons. In conclusion, gestational lead exposure in rats induces fetal toxicity and developmental abnormalities. The lead exposure also impairs development of cerebellar layers, induces structural changes, and apoptosis in the fetal cerebellar cortex. These results suggest that lead exposure during gestation is extremely toxic to developing cerebellum in rats.

  11. 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

  12. 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. PMID:27397969

  13. 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

  14. Aryl hydrocarbon receptor (AhR)-dependent regulation of pulmonary miRNA by chronic cigarette smoke exposure.

    PubMed

    Rogers, Sarah; de Souza, Angela Rico; Zago, Michela; Iu, Matthew; Guerrina, Necola; Gomez, Alvin; Matthews, Jason; Baglole, Carolyn J

    2017-01-12

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for its toxic responses to man-made pollutants such as dioxin. More recently, the AhR has emerged as a suppressor of inflammation, oxidative stress and apoptosis from cigarette smoke by mechanisms that may involve the regulation of microRNA. However, little is known about the AhR regulation of miRNA expression in the lung in response to inhaled toxicants. Therefore, we exposed Ahr(-/-) and Ahr(+/-) mice to cigarette smoke for 4 weeks and evaluated lung miRNA expression by PCR array. There was a dramatic regulation of lung miRNA by the AhR in the absence of exogenous ligand. In response to cigarette smoke, there were more up-regulated miRNA in Ahr(-/-) mice compared to Ahr(+/-) mice, including the cancer-associated miRNA miR-96. There was no significant change in the expression of the AhR regulated proteins HuR and cyclooxygenase-2 (COX-2). There were significant increases in the anti-oxidant gene sulfiredoxin 1 (Srxn1) and FOXO3a- predicted targets of miR-96. Collectively, these data support a prominent role for the AhR in regulating lung miRNA expression. Further studies to elucidate a role for these miRNA may further uncover novel biological function for the AhR in respiratory health and disease.

  15. 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…

  16. 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

  17. 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.

  18. 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.

  19. Aryl hydrocarbon receptor (AhR)-dependent regulation of pulmonary miRNA by chronic cigarette smoke exposure

    PubMed Central

    Rogers, Sarah; de Souza, Angela Rico; Zago, Michela; Iu, Matthew; Guerrina, Necola; Gomez, Alvin; Matthews, Jason; Baglole, Carolyn J.

    2017-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for its toxic responses to man-made pollutants such as dioxin. More recently, the AhR has emerged as a suppressor of inflammation, oxidative stress and apoptosis from cigarette smoke by mechanisms that may involve the regulation of microRNA. However, little is known about the AhR regulation of miRNA expression in the lung in response to inhaled toxicants. Therefore, we exposed Ahr−/− and Ahr+/− mice to cigarette smoke for 4 weeks and evaluated lung miRNA expression by PCR array. There was a dramatic regulation of lung miRNA by the AhR in the absence of exogenous ligand. In response to cigarette smoke, there were more up-regulated miRNA in Ahr−/− mice compared to Ahr+/− mice, including the cancer-associated miRNA miR-96. There was no significant change in the expression of the AhR regulated proteins HuR and cyclooxygenase-2 (COX-2). There were significant increases in the anti-oxidant gene sulfiredoxin 1 (Srxn1) and FOXO3a- predicted targets of miR-96. Collectively, these data support a prominent role for the AhR in regulating lung miRNA expression. Further studies to elucidate a role for these miRNA may further uncover novel biological function for the AhR in respiratory health and disease. PMID:28079158

  20. 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.

  1. 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…

  2. 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.

  3. 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

  4. 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...

  5. Effects of Daytime Exposure to Light from Blue-Enriched Light-Emitting Diodes on the Nighttime Melatonin Amplitude and Circadian Regulation of Rodent Metabolism and Physiology

    PubMed Central

    Dauchy, Robert T; Wren-Dail, Melissa A; Hoffman, Aaron E; Hanifin, John P; Warfield, Benjamin; Brainard, George C; Hill, Steven M; Belancio, Victoria P; Dauchy, Erin M; Blask, David E

    2016-01-01

    Regular cycles of exposure to light and dark control pineal melatonin production and temporally coordinate circadian rhythms of metabolism and physiology in mammals. Previously we demonstrated that the peak circadian amplitude of nocturnal blood melatonin levels of rats were more than 6-fold higher after exposure to cool white fluorescent (CWF) light through blue-tinted (compared with clear) rodent cages. Here, we evaluated the effects of light-phase exposure of rats to white light-emitting diodes (LED), which emit light rich in the blue-appearing portion of the visible spectrum (465–485 nm), compared with standard broad-spectrum CWF light, on melatonin levels during the subsequent dark phase and on plasma measures of metabolism and physiology. Compared with those in male rats under a 12:12-h light:dark cycle in CWF light, peak plasma melatonin levels at the middark phase (time, 2400) in rats under daytime LED light were over 7-fold higher, whereas midlight phase levels (1200) were low in both groups. Food and water intakes, body growth rate, and total fatty acid content of major metabolic tissues were markedly lower, whereas protein content was higher, in the LED group compared with CWF group. Circadian rhythms of arterial plasma levels of total fatty acids, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were generally lower in LED-exposed rats. Therefore, daytime exposure of rats to LED light with high blue emissions has a marked positive effect on the circadian regulation of neuroendocrine, metabolic, and physiologic parameters associated with the promotion of animal health and wellbeing and thus may influence scientific outcomes. PMID:27780004

  6. Effects of Daytime Exposure to Light from Blue-Enriched Light-Emitting Diodes on the Nighttime Melatonin Amplitude and Circadian Regulation of Rodent Metabolism and Physiology.

    PubMed

    Dauchy, Robert T; Wren-Dail, Melissa A; Hoffman, Aaron E; Hanifin, John P; Warfield, Benjamin; Brainard, George C; Hill, Steven M; Belancio, Victoria P; Dauchy, Erin M; Blask, David E

    2016-01-01

    Regular cycles of exposure to light and dark control pineal melatonin production and temporally coordinate circadian rhythms of metabolism and physiology in mammals. Previously we demonstrated that the peak circadian amplitude of nocturnal blood melatonin levels of rats were more than 6-fold higher after exposure to cool white fluorescent (CWF) light through blue-tinted (compared with clear) rodent cages. Here, we evaluated the effects of light-phase exposure of rats to white light-emitting diodes (LED), which emit light rich in the blue-appearing portion of the visible spectrum (465-485 nm), compared with standard broadspectrum CWF light, on melatonin levels during the subsequent dark phase and on plasma measures of metabolism and physiology. Compared with those in male rats under a 12:12-h light:dark cycle in CWF light, peak plasma melatonin levels at the middark phase (time, 2400) in rats under daytime LED light were over 7-fold higher, whereas midlight phase levels (1200) were low in both groups. Food and water intakes, body growth rate, and total fatty acid content of major metabolic tissues were markedly lower, whereas protein content was higher, in the LED group compared with CWF group. Circadian rhythms of arterial plasma levels of total fatty acids, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were generally lower in LED-exposed rats. Therefore, daytime exposure of rats to LED light with high blue emissions has a marked positive effect on the circadian regulation of neuroendocrine, metabolic, and physiologic parameters associated with the promotion of animal health and wellbeing and thus may influence scientific outcomes.

  7. 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

  8. Enhanced ability of TRPV1 channels in regulating glutamatergic transmission after repeated morphine exposure in the nucleus accumbens of rat.

    PubMed

    Zhang, Haitao; Jia, Dong; Wang, Yuan; Qu, Liang; Wang, Xuelian; Song, Jian; Heng, Lijun; Gao, Guodong

    2017-04-01

    Glutamatergic projections to nucleus accumbens (NAc) drive drug-seeking behaviors during opioids withdrawal. Modulating glutamatergic neurotransmission provides a novel pharmacotherapeutic avenue for treatment of opioids dependence. Great deals of researches have verified that transient receptor potential vanilloid 1 (TRPV1) channels alters synaptic transmitter release and regulate neural plasticity. In the present study, whole-cell patch clamp recordings were adopted to examine the activity of TRPV1 Channels in regulating glutamate-mediated excitatory postsynaptic currents (EPSCs) in NAc of rat during morphine withdrawal for 3days and 3weeks. The data showed that the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and the amplitudes of evoked excitatory postsynaptic currents (eEPSCs) were increased during morphine withdrawal after applied with capsaicin (TRPV1 agonist). Capsaicin decreased the paired pulse ratio (PPR) and increased sEPSCs frequency but not their amplitudes suggesting a presynaptic locus of action during morphine withdrawal. All these effects were fully blocked by the TRPV1 antagonist Capsazepine. Additionally, In the presence of AM251 (CB1 receptor antagonist), depolarization-induced release of endogenous cannabinoids activated TRPV1 channels to enhance glutamatergic neurotransmission during morphine withdrawal. The functional enhancement of TRPV1 Channels in facilitating glutamatergic transmission was not recorded in dorsal striatum. Our findings demonstrate the ability of TRPV1 in regulating excitatory glutamatergic transmission is enhanced during morphine withdrawal in NAc, which would deepen our understanding of glutamatergic modulation during opioids withdrawal.

  9. 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

  10. 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

  11. Cellular crosstalk between airway epithelial and endothelial cells regulates barrier functions during exposure to double‐stranded RNA

    PubMed Central

    Reale, Riccardo; Held, Marie; Loxham, Matthew; Millar, Timothy M.; Collins, Jane E.; Swindle, Emily J.; Morgan, Hywel; Davies, Donna E.

    2017-01-01

    Abstract Introduction The epithelial and endothelial barriers of the airway mucosa are critical for regulation of tissue homeostasis and protection against pathogens or other tissue damaging agents. In response to a viral infection, epithelial cells must signal to the endothelium to initiate immune cell recruitment. This is a highly temporal regulated process; however, the mechanisms of this cross‐talk are not fully understood. Methods In a close‐contact co‐culture model of human airway epithelial and endothelial cells, cellular crosstalk was analyzed using transepithelial electrical resistance (TER) measurements, immunofluorescence, electron microscopy, and ELISA. Viral infections were simulated by exposing airway epithelial cells apically to double‐stranded RNA (Poly(I:C)). Using a microfluidic culture system, the temporal release of mediators was analyzed in the co‐culture model. Results Within 4 h of challenge, double‐stranded RNA induced the release of TNF‐α by epithelial cells. This activated endothelial cells by triggering the release of the chemoattractant CX3CL1 (fractalkine) by 8 h post‐challenge and expression of adhesion molecules E‐selectin and ICAM‐1. These responses were significantly reduced by neutralising TNF‐α. Conclusion By facilitating kinetic profiling, the microfluidic co‐culture system has enabled identification of a key signaling mechanism between the epithelial and endothelial barriers. Better understanding of cell–cell cross‐talk and its regulatory mechanisms has the potential to identify new therapeutic strategies to control airway inflammation. PMID:28250924

  12. Embryonic exposure to ethanol disturbs regulation of mitotic spindle orientation via GABA(A) receptors in neural progenitors in ventricular zone of developing neocortex.

    PubMed

    Tochitani, Shiro; Sakata-Haga, Hiromi; Fukui, Yoshihiro

    2010-03-19

    Neural progenitors in the ventricular zone of the developing neocortex divide oriented either parallel or perpendicular to the ventricular surface based on their mitotic spindle orientation. It has been shown that the cleavage plane orientation is developmentally regulated and plays a crucial role in cell fate determination of neural progenitors or the maintenance of the proliferative ventricular zone during neocortical development. We tested if fetal exposure to ethanol, the most widely used psychoactive agent and a potent teratogen that may cause malformation in the central nervous system, alters mitotic cleavage orientation of the neural progenitors at the apical surface of the ventricular zone in the developing neocortex. Fetal exposure to ethanol on E10.5 and 11.5 increased the occurrence frequency of a horizontal cleavage plane that is parallel to the ventricular surface on E 12.5. Administration of picrotoxin, a GABA(A) receptor antagonist, prior to ethanol administration canceled the effect of ethanol with the frequency of horizontal division similar to the control level, although picrotoxin itself did not show any effect on cleavage plane orientation. Phenobarbital, a GABA(A) receptor agonist, induced horizontal cleavage to an extent similar to that induced by ethanol administration. (+)MK801, an antagonist of NMDA receptor that is another major target of ethanol in neural cells, did not affect the cleavage plane of dividing progenitors. These results suggest that fetal ethanol exposure induced alterations in the cleavage plane orientation of neural progenitors in the ventricular zone of the neocortex via the enhancement of the function of GABA(A) receptors.

  13. Alteration of cytochrome P450 1 regulation and HSP 70 level in brain of juvenile common carp (Cyprinus carpio) after chronic exposure to tributyltin.

    PubMed

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

    2016-02-01

    Tributyltin (TBT), a toxic contaminant in aquatic environments, has bio-accumulated in aquatic food webs throughout the world and can be found at toxic levels in some biota. However, the molecular mechanisms and effects of TBT are not fully understood. The aim of the present study was to investigate the effect of long-term exposure of TBT on cytochrome P450 (CYP450) 1 regulation and heat-shock proteins (HSPs) profiling in brain of freshwater teleost. The effects of long-term exposure to TBT on mRNA expression of cytochrome P450 (CYP450) 1 family genes and ethoxyresorufin O-deethylase (EROD) activity in the brain of common carp were evaluated, as well as HSP 70 level. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L) for 15, 30, and 60 days. Based on the results, long-term exposure (more than 15 days) to TBT could lead to obvious physiological-biochemical responses (based on EROD activity, HSP 70 level and CYP450 1 family genes expression). The mRNA expression of CYP450 1 family genes (CYP1A, CYP1B, CYP1C1 and CYP1C2) suggested that CYP1A was to accommodate most EROD activity in fish, but other CYP450 forms also involved in this proceeding. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity and could be used as potential biomarkers for monitoring the TBT pollution in the field.

  14. Combustion smoke exposure induces up-regulated expression of vascular endothelial growth factor, aquaporin 4, nitric oxide synthases and vascular permeability in the retina of adult rats.

    PubMed

    Zou, Y Y; Lu, J; Poon, D J F; Kaur, C; Cao, Q; Teo, A L; Ling, E A

    2009-05-19

    Retinal cells respond to various experimental stimuli including hypoxia, yet it remains to be investigated whether they react to smoke inhalation. We show here that retinal cells in rats, notably the ganglion cells, Müller cells, astrocytes and blood vessels responded vigorously to a smoke challenge. The major changes included up-regulated expression of vascular endothelial growth factor (VEGF), aquaporin 4 (AQP4) and nitric oxide synthase (NOS). VEGF expression was localized in the ganglion cells, Müller cells, astrocytes and associated blood vessels. AQP4 was markedly enhanced in both astrocytes and Müller cells. Increase in vascular permeability after smoke exposure was evidenced by extravasation of serum derived rhodamine isothiocyanate which was internalized by Müller cells and ganglion cells. The tracer leakage was attenuated by aminoguanidine and N(G)-nitro-L-arginine methyl ester (L-NAME) treatment which suppressed retinal tissue NOS and nitric oxide (NO) levels concomitantly. It is suggested that VEGF, AQP4 and NO are involved in increased vascular permeability following acute smoke exposure in which hypoxia was ultimately implicated as shown by blood gases analysis. NOS inhibitors effectively reduced the vascular leakage and hence may ameliorate possible retinal edema in smoke inhalation.

  15. Prenatal ethanol exposure persistently impairs N-methyl-D-aspartate receptor-dependent activation of extracellular signal-regulated kinase in the mouse dentate gyrus

    PubMed Central

    Samudio-Ruiz, Sabrina L.; Allan, Andrea M.; Valenzuela, C. Fernando; Perrone-Bizzozero, Nora I.; Caldwell, Kevin K.

    2009-01-01

    The dentate gyrus (DG) is the central input region to the hippocampus and is known to play an important role in learning and memory. Previous studies have shown that prenatal alcohol is associated with hippocampal-dependent learning deficits and a decreased ability to elicit long term potentiation (LTP) in the DG in adult animals. Given that activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling cascade by N-methyl-D-aspartate (NMDA) receptors is required for various forms of learning and memory, as well as LTP, in hippocampal regions, including the DG, we hypothesized that fetal alcohol-exposed (FAE) adult animals would have deficits in hippocampal NMDA receptor-dependent ERK1/2 activation. We used immunoblotting and immunohistochemistry techniques to detect NMDA-stimulated ERK1/2 activation in acute hippocampal slices prepared from adult FAE mice. We present the first evidence linking prenatal alcohol exposure to deficits in NMDA receptor-dependent ERK1/2 activation specifically in the DG of adult offspring. This deficit may account for the LTP deficits previously observed in the DG, as well as the life-long cognitive deficits, associated with prenatal alcohol exposure. PMID:19317851

  16. Perinatal exposure to bisphenol A modifies the transcriptional regulation of the β-Casein gene during secretory activation of the rat mammary gland.

    PubMed

    Altamirano, Gabriela A; Ramos, Jorge G; Gomez, Ayelen L; Luque, Enrique H; Muñoz-de-Toro, Monica; Kass, Laura

    2017-01-05

    With the aim to analyze whether bisphenol A (BPA) modifies β-Casein (β-Cas) synthesis and transcriptional regulation in perinatally exposed animals, here, pregnant F0 rats were orally exposed to 0, 0.6 or 52 μg BPA/kg/day from gestation day 9 until weaning. Then, F1 females were bred and mammary glands were obtained on lactation day 2. Perinatal BPA exposure decreased β-Cas expression without modifying the activation of prolactin receptor. It also decreased the expression of glucocorticoid receptor in BPA52-exposed dams and β1 and α6 integrins as well as dystroglycan in both BPA groups. In addition, BPA exposure altered the expression of histone-modifying enzymes and induced histone modifications and DNA methylation in the promoter, enhancer and exon VII of the β-Cas gene. An impaired crosstalk between the extracellular matrix and lactogenic hormone signaling pathways and epigenetic modifications of the β-Cas gene could be the molecular mechanisms by which BPA decreased β-Cas expression.

  17. Post-veraison sunlight exposure induces MYB-mediated transcriptional regulation of anthocyanin and flavonol synthesis in berry skins of Vitis vinifera

    PubMed Central

    Matus, José Tomás; Loyola, Rodrigo; Vega, Andrea; Peña-Neira, Alvaro; Bordeu, Edmundo; Arce-Johnson, Patricio; Alcalde, José Antonio

    2009-01-01

    Anthocyanins, flavan-3-ols, and flavonols are the three major classes of flavonoid compounds found in grape berry tissues. Several viticultural practices increase flavonoid content in the fruit, but the underlying genetic mechanisms responsible for these changes have not been completely deciphered. The impact of post-veraison sunlight exposure on anthocyanin and flavonol accumulation in grape berry skin and its relation to the expression of different transcriptional regulators known to be involved in flavonoid synthesis was studied. Treatments consisting of removing or moving aside the basal leaves which shade berry clusters were applied. Shading did not affect sugar accumulation or gene expression of HEXOSE TRANSPORTER 1, although in the leaf removal treatment, these events were retarded during the first weeks of ripening. Flavonols were the most drastically reduced flavonoids following shading and leaf removal treatments, related to the reduced expression of FLAVONOL SYNTHASE 4 and its putative transcriptional regulator MYB12. Anthocyanin accumulation and the expression of CHS2, LDOX, OMT, UFGT, MYBA1, and MYB5a genes were also affected. Other regulatory genes were less affected or not affected at all by these treatments. Non-transcriptional control mechanisms for flavonoid synthesis are also suggested, especially during the initial stages of ripening. Although berries from the leaf removal treatment received more light than shaded fruits, malvidin-3-glucoside and total flavonol content was reduced compared with the treatment without leaf removal. This work reveals that flavonol-related gene expression responds rapidly to field changes in light levels, as shown by the treatment in which shaded fruits were exposed to light in the late stages of ripening. Taken together, this study establishes MYB-specific responsiveness for the effect of sun exposure and sugar transport on flavonoid synthesis. PMID:19129169

  18. Expression pattern of potential biomarker genes related to growth, ion regulation and stress in response to ammonia exposure, food deprivation and exercise in common carp (Cyprinus carpio).

    PubMed

    Sinha, Amit Kumar; Diricx, Marjan; Chan, Lai Pong; Liew, Hon Jung; Kumar, Vikas; Blust, Ronny; De Boeck, Gudrun

    2012-10-15

    Waterborne ammonia has become a persistent pollutant of aquatic habitats. During certain periods (e.g. winter), food deprivation may occur simultaneously in natural water. Additionally, under such stressful circumstances, fish may be enforced to swim at a high speed in order to catch prey, avoid predators and so on. Consequently, fish need to cope with all these stressors by altering physiological processes which in turn are controlled by their genes. In this present study, toxicogenomic analyses using real time PCR was used to characterize expression patterns of potential biomarker genes controlling growth, ion regulation and stress responses in common carp subjected to elevated ammonia (1 mg/L; Flemish water quality guideline for surface water) following periods of feeding (2% body weight) and fasting (unfed for 7 days prior to sampling). Both feeding groups of fish were exposed to high environment ammonia (HEA) for 0 h (control), 3h, 12h, 1 day, 4 days, 10 days, 21 days and 28 days, and were sampled after performing swimming at different speeds (routine versus exhaustive). Results show that the activity and expression of Na(+)/K(+)-ATPase, an important branchial ion regulatory enzyme, was increased after 4-10 days of exposure. Effect of HEA was also evident on expression patterns of other ion-regulatory hormone and receptor genes; prolactin and cortisol receptor mRNA level(s) were down-regulated and up-regulated respectively after 4, 10 and 21 days. Starvation and exhaustive swimming, the additional challenges in present study significantly further enhanced the HEA effect on the expression of these two genes. mRNA transcript of growth regulating hormone and receptor genes such as Insulin-like growth factor I, growth hormone receptor, and the thyroid hormone receptor were reduced in response to HEA and the effect of ammonia was exacerbated in starved fish, with levels that were remarkably reduced compared to fed exposed fish. However, the expression of the growth

  19. Federal Supervisors and Poor Performers

    DTIC Science & Technology

    1999-07-01

    This report looks at the prevalence of poor performance in the Federal workplace from the perspective of employees and supervisors. The report also...examines what supervisors do about poor performers, the effects of supervisors’ actions, and the factors that influence supervisors’ decisions about how they will handle inadequate performance.

  20. The Etiology of Poor Neighborhoods.

    ERIC Educational Resources Information Center

    Greenberg, Stanley B.

    The inner city aggregations of blacks, Appalachian whites, and Mexicans are not simply the focal points for short-term instability or remedial governmental programs: they are the first native American urban poor. The poor neighborhoods of America's inner city are a result of three great population movements. One originated in the Atlantic Coastal…

  1. 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

  2. Turkish Final Year Medical Students’ Exposure to and Attitudes Concerning Drug Company Interactions: A Perspective from a Minimally Regulated Environment for Medical Students

    PubMed Central

    Beyhun, Nazim Ercument; Kolayli, Cevriye Ceyda; Can, Gamze; Topbas, Murat

    2016-01-01

    Interactions between drug companies and medical students may affect evidence-based medical practice and patient safety. The aim of this study was to assess drug company–medical student interactions in a medical faculty where limited specific national or institutional regulations apply between drug companies and medical students. The objectives of the study were to determine the exposure and attitudes of final year medical students in terms of drug company–medical student and physician interactions, to identify factors affecting those attitudes and to provide data for policymakers working on the regulation of interactions between drug companies and medical students. This anonymous questionnaire-based study of 154 medical final year medical students at the Karadeniz Technical University Medical Faculty, Trabzon, Turkey, in April and May 2015 attracted a response rate of 92.2% (n/N, 154/164). Exposure to interaction with a pharmaceutical representative was reported by 90.3% (139/154) of students, and 68.8% (106/154) reported experiencing such interaction alongside a resident. In addition, 83.7% (128/153) of students reported an interaction during internship. Furthermore, 69.9% (107/153) of students agreed that interactions influence physicians’ prescription preferences, while 33.1% (51/154) thought that a medical student should never accept a gift from a drug company and 24.7% (38/154) agreed with the proposition that “drug companies should not hold activities in medical faculties”. Students with rational prescription training expressed greater agreement with the statement “I am skeptical concerning the information provided by drug companies during interactions” than those who had not received such training, and this finding was supported by logistic regression [O.R.(C.I), p -3.7(1.2–11.5), p = 0.022]. Acceptance of advertisement brochures was found to significantly reduce the level of agreement with the proposition that “A physician should not

  3. Turkish Final Year Medical Students' Exposure to and Attitudes Concerning Drug Company Interactions: A Perspective from a Minimally Regulated Environment for Medical Students.

    PubMed

    Beyhun, Nazim Ercument; Kolayli, Cevriye Ceyda; Can, Gamze; Topbas, Murat

    2016-01-01

    Interactions between drug companies and medical students may affect evidence-based medical practice and patient safety. The aim of this study was to assess drug company-medical student interactions in a medical faculty where limited specific national or institutional regulations apply between drug companies and medical students. The objectives of the study were to determine the exposure and attitudes of final year medical students in terms of drug company-medical student and physician interactions, to identify factors affecting those attitudes and to provide data for policymakers working on the regulation of interactions between drug companies and medical students. This anonymous questionnaire-based study of 154 medical final year medical students at the Karadeniz Technical University Medical Faculty, Trabzon, Turkey, in April and May 2015 attracted a response rate of 92.2% (n/N, 154/164). Exposure to interaction with a pharmaceutical representative was reported by 90.3% (139/154) of students, and 68.8% (106/154) reported experiencing such interaction alongside a resident. In addition, 83.7% (128/153) of students reported an interaction during internship. Furthermore, 69.9% (107/153) of students agreed that interactions influence physicians' prescription preferences, while 33.1% (51/154) thought that a medical student should never accept a gift from a drug company and 24.7% (38/154) agreed with the proposition that "drug companies should not hold activities in medical faculties". Students with rational prescription training expressed greater agreement with the statement "I am skeptical concerning the information provided by drug companies during interactions" than those who had not received such training, and this finding was supported by logistic regression [O.R.(C.I), p -3.7(1.2-11.5), p = 0.022]. Acceptance of advertisement brochures was found to significantly reduce the level of agreement with the proposition that "A physician should not accept any gift from a

  4. Regulation of Sirt1/Nrf2/TNF-α signaling pathway by luteolin is critical to attenuate acute mercuric chloride exposure induced hepatotoxicity

    PubMed Central

    Yang, Daqian; Tan, Xiao; Lv, Zhanjun; Liu, Biying; Baiyun, Ruiqi; Lu, Jingjing; Zhang, Zhigang

    2016-01-01

    Inorganic mercury, though a key component of pediatric vaccines, is an environmental toxicant threatening human health via accumulating oxidative stress in part. Luteolin has been of great interest because of its antiinflammatory, anticarcinogenic and antioxidative effects. Here we hypothesized that luteolin would attenuate hepatotoxicity induced by acute inorganic mercury exposure. Kunming mice were treated with luteolin (100 mg/kg) 24 h after administration of 4 mg/kg mercuric chloride (HgCl2). The results showed that luteolin ameliorated HgCl2 induced anemia and hepatotoxicity, regulating radical oxygen species (ROS) production and hepatocyte viability in vitro and oxidative stress and apoptosis in vivo. Furthermore, luteolin reversed the changes in levels of inflammation- and apoptosis-related proteins involving NF-κB, TNF-α, Sirt1, mTOR, Bax, p53, and Bcl-2, and inhibited p38 MAPK activation. Luteolin enhanced antioxidant defense system based on Keap1, Nrf2, HO-1, NQO1, and KLF9. Moreover, luteolin did not affect miRNA-146a expression. Collectively, our findings, for the first time, elucidate a precise mechanism for attenuation of HgCl2-induced liver dysfunction by dietary luteolin via regulating Sirt1/Nrf2/TNF-α signaling pathway, and provide a foundation for further study of luteolin as a novel therapeutic agent against inorganic mercury poisoning. PMID:27853236

  5. Proteomic analysis of a model unicellular green alga, Chlamydomonas reinhardtii, during short-term exposure to irradiance stress reveals significant down regulation of several heat-shock proteins.

    PubMed

    Mahong, Bancha; Roytrakul, Suttiruk; Phaonaklop, Narumon; Wongratana, Janewit; Yokthongwattana, Kittisak

    2012-03-01

    Oxygenic photosynthetic organisms often suffer from excessive irradiance, which cause harmful effects to the chloroplast proteins and lipids. Photoprotection and the photosystem II repair processes are the mechanisms that plants deploy to counteract the drastic effects from irradiance stress. Although the protective and repair mechanisms seemed to be similar in most plants, many species do confer different level of tolerance toward high light. Such diversity may originate from differences at the molecular level, i.e., perception of the light stress, signal transduction and expression of stress responsive genes. Comprehensive analysis of overall changes in the total pool of proteins in an organism can be performed using a proteomic approach. In this study, we employed 2-DE/LC-MS/MS-based comparative proteomic approach to analyze total proteins of the light sensitive model unicellular green alga Chlamydomonas reinhardtii in response to excessive irradiance. Results showed that among all the differentially expressed proteins, several heat-shock proteins and molecular chaperones were surprisingly down-regulated after 3-6 h of high light exposure. Discussions were made on the possible involvement of such down regulation and the light sensitive nature of this model alga.

  6. 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

  7. 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.

  8. 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

  9. Educational attainment in poor comprehenders

    PubMed Central

    Ricketts, Jessie; Sperring, Rachael; Nation, Kate

    2014-01-01

    To date, only one study has investigated educational attainment in poor (reading) comprehenders, providing evidence of poor performance on national UK school tests at age 11 years relative to peers (Cain and Oakhill, 2006). In the present study, we adopted a longitudinal approach, tracking attainment on such tests from 11 years to the end of compulsory schooling in the UK (age 16 years). We aimed to investigate the proposal that educational weaknesses (defined as poor performance on national assessments) might become more pronounced over time, as the curriculum places increasing demands on reading comprehension. Participants comprised 15 poor comprehenders and 15 controls; groups were matched for chronological age, nonverbal reasoning ability and decoding skill. Children were identified at age 9 years using standardized measures of nonverbal reasoning, decoding and reading comprehension. These measures, along with a measure of oral vocabulary knowledge, were repeated at age 11 years. Data on educational attainment were collected from all participants (n = 30) at age 11 and from a subgroup (n = 21) at 16 years. Compared to controls, educational attainment in poor comprehenders was lower at ages 11 and 16 years, an effect that was significant at 11 years. When poor comprehenders were compared to national performance levels, they showed significantly lower performance at both time points. Low educational attainment was not evident for all poor comprehenders. Nonetheless, our findings point to a link between reading comprehension difficulties in mid to late childhood and poor educational outcomes at ages 11 and 16 years. At these ages, pupils in the UK are making key transitions: they move from primary to secondary schools at 11, and out of compulsory schooling at 16. PMID:24904464

  10. Expression of genes involved in mouse lung cell differentiation/regulation after acute exposure to photons and protons with or without low-dose preirradiation.

    PubMed

    Tian, Jian; Zhao, WeiLing; Tian, Sisi; Slater, James M; Deng, Zhiyong; Gridley, Daila S

    2011-11-01

    The goal of this study was to compare the effects of acute 2 Gy irradiation with photons (0.8 Gy/min) or protons (0.9 Gy/min), both with and without pre-exposure to low-dose/low-dose-rate γ rays (0.01 Gy at 0.03 cGy/h), on 84 genes involved in stem cell differentiation or regulation in mouse lungs on days 21 and 56. Genes with a ≥1.5-fold difference in expression and P < 0.05 compared to 0 Gy controls are emphasized. Two proteins specific for lung stem cells/progenitors responsible for local tissue repair were also compared. Overall, striking differences were present between protons and photons in modulating the genes. More genes were affected by protons than by photons (22 compared to 2 and 6 compared to 2 on day 21 and day 56, respectively) compared to 0 Gy. Preirradiation with low-dose-rate γ rays enhanced the acute photon-induced gene modulation on day 21 (11 compared to 2), and all 11 genes were significantly downregulated on day 56. On day 21, seven genes (aldh2, bmp2, cdc2a, col1a1, dll1, foxa2 and notch1) were upregulated in response to most of the radiation regimens. Immunoreactivity of Clara cell secretory protein was enhanced by all radiation regimens. The number of alveolar type 2 cells positive for prosurfactant protein C in irradiated groups was higher on day 56 (12.4-14.6 cells/100) than on day 21 (8.5-11.2 cells/100) (P < 0.05). Taken together, these results showed that acute photons and protons induced different gene expression profiles in the lungs and that pre-exposure to low-dose-rate γ rays sometimes had modulatory effects. In addition, proteins associated with lung-specific stem cells/progenitors were highly sensitive to radiation.

  11. Introduction, audit and review of guidelines for delegated authorization of nuclear medicine investigations in compliance with the Ionising Radiation (Medical Exposure) Regulations 2000.

    PubMed

    Harris, A M; Greaves, C D; Taylor, C M; Taylor, C; Segasby, C A; Tindale, W B

    2003-08-01

    The introduction of the Ionising Radiation (Medical Exposure) Regulations 2000 in Great Britain required every nuclear medicine investigation to be justified by a practitioner holding an appropriate Administration of Radioactive Substances Committee (ARSAC) certificate. The task of authorizing the radiation exposure may be performed by the practitioner (direct authorization) or delegated to an appropriately trained operator working to written guidelines approved by the practitioner (delegated authorization). In this study, we look at the process of implementation, audit and review of a set of Delegated Authorization Guidelines (DAG). The process of drafting the DAG is outlined. Following the introduction of the DAG, an audit of nuclear medicine referrals was performed at two sites for a period of 3 months. Each referral was compared with the DAG to determine whether it matched the criteria set out. If it did not match, it was further categorized as being due to: (1) insufficient referral information; or (2) clinical indication not included in the DAG. All non-matching requests were reviewed by the practitioner. Four hundred and thirty-seven of 632 (69%) referrals fitted the DAG, 12% (n=75) required clarification from the referrer before fitting with the criteria and 19% (n=120) were directly authorized by the practitioner. From those referrals that were directly authorized, some additional indications were identified and the DAG were subsequently revised. In conclusion, a delegated authorization procedure for nuclear medicine investigations can be implemented successfully. Regular audit is essential. This study identified the need to improve the format of the request card and to obtain additional referral information from the referrer.

  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. Transcriptional regulation of three EIN3-like genes of carnation (Dianthus caryophyllus L. cv. Improved White Sim) during flower development and upon wounding, pollination, and ethylene exposure.

    PubMed

    Iordachescu, Mihaela; Verlinden, Sven

    2005-08-01

    Using a combination of approaches, three EIN3-like (EIL) genes DC-EIL1/2 (AY728191), DC-EIL3 (AY728192), and DC-EIL4 (AY728193) were isolated from carnation (Dianthus caryophyllus) petals. DC-EIL1/2 deduced amino acid sequence shares 98% identity with the previously cloned and characterized carnation DC-EIL1 (AF261654), 62% identity with DC-EIL3, and 60% identity with DC-EIL4. DC-EIL3 deduced amino acid sequence shares 100% identity with a previously cloned carnation gene fragment, Dc106 (CF259543), 61% identity with Dianthus caryophyllus DC-EIL1 (AF261654), and 59% identity with DC-EIL4. DC-EIL4 shared 60% identity with DC-EIL1 (AF261654). Expression analyses performed on vegetative and flower tissues (petals, ovaries, and styles) during growth and development and senescence (natural and ethylene-induced) indicated that the mRNA accumulation of the DC-EIL family of genes in carnation is regulated developmentally and by ethylene. DC-EIL3 mRNA showed significant accumulation upon ethylene exposure, during flower development, and upon pollination in petals and styles. Interestingly, decreasing levels of DC-EIL3 mRNA were found in wounded leaves and ovaries of senescing flowers whenever ethylene levels increased. Flowers treated with sucrose showed a 2 d delay in the accumulation of DC-EIL3 transcripts when compared with control flowers. These observations suggest an important role for DC-EIL3 during growth and development. Changes in DC-EIL1/2 and DC-EIL4 mRNA levels during flower development, and upon ethylene exposure and pollination were very similar. mRNA levels of the DC-EILs in styles of pollinated flowers showed a positive correlation with ethylene production after pollination. The cloning and characterization of the EIN3-like genes in the present study showed their transcriptional regulation not previously observed for EILs.

  14. A Culture in Transition: Poor Reading and Writing Ability among Children in South African Townships.

    ERIC Educational Resources Information Center

    Pretorius, E.; Naude, H.

    2002-01-01

    This study examined factors contributing to poor literacy and numeracy development among black South African children ages 5.5 to 7 years. Findings pointed to a conglomerate of factors, namely inadequate visual-motor integration, poor visual analysis and synthesis, poor fine motor development, and inadequate exposure to mediated reading and…

  15. Rb silencing mediated by the down-regulation of MeCP2 is involved in cell transformation induced by long-term exposure to hydroquinone.

    PubMed

    Liu, Linhua; Ling, Xiaoxuan; Wu, Minhua; Chen, Jialong; Chen, Shaoqiao; Tan, Qiang; Chen, Jiansong; Liu, Jiaxian; Zou, Fei

    2017-02-01

    Hydroquinone (HQ), a metabolite of benzene, is a well-known human carcinogen; however, its molecular mechanisms of action remain unclear. MeCP2 has been traditionally described as a transcriptional repressor, though growing evidence indicates that it also activates gene expression. Here, we investigated whether some epigenetic machinery genes are aberrantly expressed as target tumor suppressor genes in HQ-transformed TK6 lymphoblastoid cells. Our results showed that treatment with 5-Aza-2'-deoxycytidine or trichostatin A enhanced the expression of Rb, resulting in cell arrest in G1-phase, and subsequently, an increase in apoptosis and a decrease in cell growth. Moreover, we hypothesised that Rb was silenced by the down-regulation of MeCP2 in HQ-transformed cells, resulting in the dynamic expression of Rb and epigenetic machinery proteins in HQ-transformed cells at different time points. The expression of Rb and MeCP2 in patients with B-cell non-Hodgkin's lymphoma (B-NHL) showed that positive staining for MeCP2 or Rb was significantly lower in B-NHL tumor tissues, and these changes were significantly and negatively correlated with the grade of B-NHL. The restoration of MeCP2 in HQ-transformed cells enhanced the expression of Rb, promoted cell apoptosis, and inhibited cell growth. The changes in the expression patterns of MeCP2 and Rb were inversely correlated with the degree of DNA methylation. A ChiP assay revealed that MeCP2 proteins were recruited to the Rb promoter with lower 5'-methylcytosine levels. In conclusion, we demonstrated that the down-regulation of MeCP2 silences Rb, a process involved in cell transformation resulting from long-term exposure to HQ. © 2016 Wiley Periodicals, Inc.

  16. 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.

  17. 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 ...

  18. Characterization of hydra type IV collagen. Type IV collagen is essential for head regeneration and its expression is up-regulated upon exposure to glucose.

    PubMed

    Fowler, S J; Jose, S; Zhang, X; Deutzmann, R; Sarras, M P; Boot-Handford, R P

    2000-12-15

    Hydra vulgaris mesoglea is a primitive basement membrane that also exhibits some features of an interstitial matrix. We have characterized cDNAs that encode the full-length hydra alpha1(IV) chain. The 5169-base pair transcript encodes a protein of 1723 amino acids, including an interrupted 1455-residue collagenous domain and a 228-residue C-terminal noncollagenous domain. N-terminal sequence analyses of collagen IV peptides suggest the molecule is homotrimeric. Denatured hydra type IV collagen protein occurs as dimers and higher order aggregates held together by nonreducible cross-links. Hydra collagen IV exhibits no functional evidence for the presence of a 7 S domain. Type IV collagen is expressed by the ectoderm along the entire longitudinal axis of the animal but is most intense at the base of the tentacles at the site of battery cell transdifferentiation. Antisense studies show that inhibition of collagen IV translation causes a blockage in head regeneration, indicating its importance in normal hydra development. Exposure of adult hydra to 15 mm glucose resulted in up-regulation of type IV collagen mRNA levels within 48 h and significant thickening of the mesoglea within 14 days, suggesting that basement membrane thickening seen in diabetes may be, in evolutionary terms, an ancient glucose-mediated response.

  19. 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

  20. Ammonia inhibits cAMP-regulated intestinal Cl- transport. Asymmetric effects of apical and basolateral exposure and implications for epithelial barrier function.

    PubMed Central

    Prasad, M; Smith, J A; Resnick, A; Awtrey, C S; Hrnjez, B J; Matthews, J B

    1995-01-01

    The colon, unlike most organs, is normally exposed to high concentrations of ammonia, a weak base which exerts profound and diverse biological effects on mammalian cells. The impact of ammonia on intestinal cell function is largely unknown despite its concentration of 4-70 mM in the colonic lumen. The human intestinal epithelial cell line T84 was used to model electrogenic Cl- secretion, the transport event which hydrates mucosal surfaces and accounts for secretory diarrhea. Transepithelial transport and isotopic flux analysis indicated that physiologically-relevant concentrations of ammonia (as NH4Cl) markedly inhibit cyclic nucleotide-regulated Cl- secretion but not the response to the Ca2+ agonist carbachol. Inhibition by ammonia was 25-fold more potent with basolateral compared to apical exposure. Ion substitution indicated that the effect of NH4Cl was not due to altered cation composition or membrane potential. The site of action of ammonia is distal to cAMP generation and is not due simply to cytoplasmic alkalization. The results support a novel role for ammonia as an inhibitory modulator of intestinal epithelial Cl- secretion. Secretory responsiveness may be dampened in pathological conditions associated with increased mucosal permeability due to enhanced access of lumenal ammonia to the basolateral epithelial compartment. Images PMID:7593599

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

    PubMed

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

    2013-10-01

    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 (DA) 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 DA activity. However, effects of PAE on the interaction between HPA and DA systems have not been investigated. The present study examined PAE effects on basal regulation of central stress and DA 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 24h 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 mRNA throughout the hippocampus, and an attenuated decrease in DA-R expression throughout the nucleus accumbens and striatum compared to CVS-exposed control

  2. 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

  3. 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

  4. Blue metal-poor stars

    NASA Astrophysics Data System (ADS)

    Preston, George W.; Sneden, Christopher

    2004-12-01

    We review the discovery of blue metal-poor (BMP) stars and the resolution of this population into blue stragglers and intermediate-age Main-Sequence stars by use of binary fractions. We show that the specific frequencies of blue stragglers in the halo field and in globular clusters differ by an order of magnitude. We attribute this difference to the different modes of production of these two populations. We report carbon and s-process enrichment among very metal-poor field blue stragglers and discuss how this result can be used to further resolve field blue stragglers into groups formed during RGB and AGB evolution of their erstwhile primary companions.

  5. The Power of Poor Communications

    ERIC Educational Resources Information Center

    Schaub, Alfred R.

    1975-01-01

    Most breakdowns in communications are the result of the quest for power on behalf of organization members, not the result of poor communications training. Organizational power may be accrued by withholding information, sabotaging communications, refusing to communicate bad news to superiors, and avoiding confrontations by not communicating at all.…

  6. Standard and Poor's Rich Website

    ERIC Educational Resources Information Center

    DiMaria, Frank

    2006-01-01

    To help parents investigate and locate quality school districts and to help policy-makers, principals, and superintendents to make well-informed decisions about education, Standard and Poor's has launched a website called SchoolMatters.com. It is recognized by the U.S. Department of Education and featured on its website (www.ed.gov/parents).…

  7. 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)

  8. Educating Canada's Urban Poor Children.

    ERIC Educational Resources Information Center

    Maynes, Bill; Foster, Rosemary

    2000-01-01

    Presents six critical thoughts and questions about educating poor urban children in Canada. These thoughts were derived from the development of a directory of Canadian educational poverty programs. Findings from that study emphasize the increasing diversity of the student population, the importance of temporary and large-scale funding, and the…

  9. 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.

  10. Allergen-specific regulation of allergic rhinitis in mice by intranasal exposure to IgG1 monoclonal antibody Fab fragments against pathogenic allergen.

    PubMed

    Matsuoka, Daiko; Mizutani, Nobuaki; Sae-Wong, Chutha; Yoshino, Shin

    2014-09-01

    Fab fragments (Fabs) have the ability to bind to specific antigens but lack the Fc portion for binding to receptors on immune and inflammatory cells that play a critical role in allergic diseases. In the present study, we investigated whether Fabs of an allergen-specific IgG1 monoclonal antibody (mAb) inhibited allergic rhinitis in mice. BALB/c mice sensitized by intraperitoneal injections of ovalbumin (OVA) plus alum on days 0 and 14 were intranasally challenged with OVA on days 28-30, and 35. Fabs prepared by the digestion of an anti-OVA IgG1 mAb (O1-10) with papain were also intranasally administered 15min before each OVA challenge. The results showed that treatment with O1-10 Fabs significantly suppressed the sneezing frequency, associated with decrease of OVA-specific IgE in the serum and infiltration by mast cells in the nasal mucosa seen following the fourth antigenic challenge; additionally, the level of mouse mast cell protease-1, a marker of mast cell activation, in serum was decreased. Furthermore, infiltration of eosinophils and goblet cell hyperplasia in the nasal mucosa at the fourth challenge were inhibited by treatment with O1-10 Fabs. In conclusion, these results suggest that intranasal exposure to Fabs of a pathogenic antigen-specific IgG1 mAb may be effective in regulating allergic rhinitis through allergen capture by Fabs in the nasal mucosa before the interaction of the intact antibody and allergen.

  11. Health solutions for the poor.

    PubMed

    Castro, J L; Fujiwara, P I; Bhambal, P; Emaille-Léotard, N; Harries, A D

    2014-03-21

    The International Union Against Tuberculosis and Lung Disease (The Union) is the oldest international non-governmental organisation involved in the fight against tuberculosis. In 2008, the Institute of The Union was challenged to think boldly about the future and to develop a diverse work portfolio covering a wide spectrum of lung health and other disease-related problems. The vision adopted by The Union at that time was 'Health solutions for the poor'. More recently, there has been lengthy debate about the need for the Union to concentrate just on its core mandate of tuberculosis and lung health and for the Union's vision to reflect this narrower spectrum of activity as 'Lung health solutions for the poor'. In this viewpoint article we outline our reasons for believing that this narrower vision is incompatible with The Union's mission statement, and we argue that making such a change would be a mistake.

  12. IFPA Meeting 2012 Workshop Report II: epigenetics and imprinting in the placenta, growth factors and villous trophoblast differentiation, role of the placenta in regulating fetal exposure to xenobiotics during pregnancy, infection and the placenta.

    PubMed

    Ahmed, M S; Aleksunes, L M; Boeuf, P; Chung, M K; Daoud, G; Desoye, G; Díaz, P; Golos, T G; Illsley, N P; Kikuchi, K; Komatsu, R; Lao, T; Morales-Prieto, D M; Nanovskaya, T; Nobuzane, T; Roberts, C T; Saffery, R; Tamura, I; Tamura, K; Than, N G; Tomi, M; Umbers, A; Wang, B; Weedon-Fekjaer, M S; Yamada, S; Yamazaki, K; Yoshie, M; Lash, G E

    2013-03-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2012 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology: 1) epigenetics and imprinting in the placenta; 2) growth factors and villous trophoblast differentiation; 3) role of the placenta in regulating fetal exposure to xenobiotics during pregnancy; 4) infection and the placenta.

  13. IFPA Meeting 2012 Workshop Report II: Epigenetics and imprinting in the placenta, growth factors and villous trophoblast differentiation, role of the placenta in regulating fetal exposure to xenobiotics during pregnancy, infection and the placenta

    PubMed Central

    Ahmed, M.S.; Aleksunes, L.M.; Boeuf, P.; Chung, M.K.; Daoud, G.; Desoye, G.; Díaz, P.; Golos, T.G.; Illsley, N.P.; Kikuchi, K.; Komatsu, R.; Lao, T.; Morales-Prieto, D.M.; Nanovskaya, T.; Nobuzane, T.; Roberts, C.T.; Saffery, R.; Tamura, I.; Tamura, K.; Than, N.G.; Tomi, M.; Umbers, A.; Wang, B.; Weedon-Fekjaer, M.S.; Yamada, S.; Yamazaki, K.; Yoshie, M.; Lash, G.E.

    2015-01-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2012 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology: 1) epigenetics and imprinting in the placenta; 2) growth factors and villous trophoblast differentiation; 3) role of the placenta in regulating fetal exposure to xenobiotics during pregnancy; 4) infection and the placenta. PMID:23253784

  14. 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.

  15. 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

  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.

  17. [Drug access in poor countries].

    PubMed

    Sebbag, Robert

    2007-11-01

    As a responsible player in the global pharmaceutical industry, Sanofi-Aventis recognizes its special responsibility to provide poor countries with access to drugs and vaccines. This is a key component of the Group's approach to sustainable development. As such, the Access to Medicines department draws on Sanofi-Aventis' expertise in order to address major public health issues, starting with the treatment of malaria, tuberculosis, sleeping sickness, leishmaniasis and epilepsy, as well as access to vaccines. The department has four main activities: research and development of new drugs; improvement of existing treatments; information, communication and education of patients and healthcare professionals; and development of a differential pricing and distribution policy adapted to patients' income, with a "no profit-no loss" equilibrium.

  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.

  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

    2015-08-07

    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.

  20. Exposure of drugs for hypertension, diabetes, and autoimmune disease during pregnancy and perinatal outcomes: an investigation of the regulator in Japan.

    PubMed

    Sato, Ryosuke; Ikuma, Mutsuhiro; Takagi, Kazunori; Yamagishi, Yoshiaki; Asano, Junichi; Matsunaga, Yusuke; Watanabe, Hiroshi

    2015-01-01

    Assessment of perinatal effects of drug exposure during pregnancy after approval is an important issue for regulatory agencies. The study aimed to explore associations between perinatal outcomes and maternal exposure to drugs for chronic diseases, including hypertension, diabetes, and autoimmune disease.We reviewed 521 cases of adverse reactions due to drug exposure during pregnancy who were reported to the Pharmaceuticals and Medical Devices Agency, a regulatory authority in Japan. The primary outcomes were fetal and neonatal death and malformation of infants. Associations between perinatal outcomes and exposure to each drug category for hypertension, diabetes, and autoimmune disease were evaluated using logistic regression analysis.Of the 521 cases (maternal age: 15-47 years; mean 32.3 ± 5.5), fetal and neonatal deaths were reported in 159 cases (130 miscarriage; 12 stillbirth; 4, neonatal death; and 13 abortion due to medical reasons), and malformations of infants were observed in 124 cases. In contrast to the trend of association between diabetes with or without medication and fetal and neonatal death (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.17-1.36), exposure to oral antidiabetics tended to be associated with fetal and neonatal death (OR, 4.86; 95% CI, 0.81-29.2). Malformation tended to be correlated with exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (OR, 2.98; 95% CI, 0.76-11.7). This association showed trends opposite to that of the association with hypertension itself (OR, 0.42; 95% CI, 0.18-1.02) or overall antihypertensives (OR, 0.42; 95% CI, 0.15-1.13). Occurrence of multiple malformations was associated with exposure to biologics (OR, 8.46; 95% CI, 1.40-51.1), whereas there was no significant association between multiple malformations and autoimmune disease with or without medication (OR 1.07; 95% CI, 0.37-3.06).These findings suggest that drugs of different categories may have undesirable

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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

  6. 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…

  7. Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress

    PubMed Central

    Loseva, Olga; Shubbar, Emman; Haghdoost, Siamak; Evers, Bastiaan; Helleday, Thomas; Harms-Ringdahl, Mats

    2014-01-01

    The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR) exposure (5 or 15 mGy/h) of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS). We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS) is mechanistically involved. PMID:28250385

  8. 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.

  9. 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...

  10. Exposure Nomographs

    NASA Astrophysics Data System (ADS)

    Zissell, Ronald E.

    Correct exposure times may be determined from nomographs relating signal-to-noise ratio, exposure time, color, seeing, and magnitude. The equations needed to construct the nomographs are developed. Calibration techniques are discussed.

  11. 64 FR 34625 - Occupational Exposure to Tuberculosis

    Federal Register 2010, 2011, 2012, 2013, 2014

    1999-06-28

    ... Tuberculosis AGENCY: Occupational Safety and Health Administration (OSHA), Department of Labor. ACTION: Notice..., 1997, OSHA published its proposed standard to regulate occupational exposure to tuberculosis (TB) (62... preliminary risk assessment for occupational exposure to tuberculosis. DATES: Comments and data...

  12. 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.

  13. 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

  14. 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.

  15. 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...

  16. Military Exposures

    MedlinePlus

    ... Chemicals (Agent Orange, contaminated water…) Radiation (nuclear weapons, X-rays…) Air Pollutants (burn pit smoke, dust…) Occupational Hazards (asbestos, lead…) Warfare Agents (chemical and biological weapons) Exposure ...

  17. The bioethics of medical research in very poor countries.

    PubMed

    Tausig, Mark; Subedi, Sree; Subedi, Janardan

    2007-04-01

    Sociologists have had only a marginal effect on the development of bioethical principles for medical research despite their interest in the effects of social and economic inequality on health and its implications for issues of social and individual justice. In this article we review existing bioethical standards for conducting medical research in very poor countries. Given the substantial differences in individual exposure to health risks and the availability of health protective resources as well as differences in the disease burden and mortality and morbidity at the population level, it is clear that illness in poor countries can be better understood using a social causation of illness perspective. In turn we suggest that such a perspective can be useful for identifying bioethical standards that better apply in this context.

  18. Family Structure and Employment Characteristics Differentiate Poor from Near-Poor Workers.

    ERIC Educational Resources Information Center

    Dagata, Elizabeth M.

    1997-01-01

    Current Population Survey data indicate that rural workers were more likely than urban workers to be poor or near-poor. Poor and near-poor rural workers were more likely than other workers to be southern, young, and in a minority group. Barriers to livable-wage employment included low educational attainment, being a single mother, and having young…

  19. 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…

  20. EXPOSURE ANALYSIS

    EPA Science Inventory

    This proceedings chapter presents the state of the science regarding the evaluation of exposure as it relates to WQC, SQGs, and wildlife criteria (WC). . . . In summary, the exposure workgroup concluded the following: There should be greater use of mechanistic models to predict b...

  1. 7 CFR 51.779 - Poorly colored.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 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... green color....

  2. 7 CFR 51.779 - Poorly colored.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 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... green color....

  3. Maternal poly I:C exposure during pregnancy regulates TNF alpha, BDNF, and NGF expression in neonatal brain and the maternal-fetal unit of the rat.

    PubMed

    Gilmore, John H; Jarskog, L Fredrik; Vadlamudi, Swarooparani

    2005-02-01

    Maternal infection during pregnancy is associated with increased risk for neurodevelopmental disorders. Polyriboinosinic-polyribocytidilic acid (poly I:C) or saline was administered to rats to model maternal infection; levels of TNFalpha, brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) were determined by ELISA. TNFalpha was significantly increased in maternal plasma, placenta, and amniotic fluid, while it was significantly decreased in fetal liver/spleen and neonatal brain. NGF and BDNF were significantly decreased in the placenta and fetal liver/spleen. There was no change in BDNF or NGF in the fetal or neonatal brain. Changes in TNFalpha, BDNF, and NGF after maternal exposure to poly I:C represent a potential mechanism through which maternal infection increases risk for neurodevelopmental disorders.

  4. 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

  5. BIRTH CONTROL, CULTURE AND THE POOR.

    ERIC Educational Resources Information Center

    RIESSMAN, CATHERINE KOHLER

    EVIDENCE FROM STUDIES INDICATE THAT THE POOR DESIRE TO CONTROL THEIR FAMILY SIZE AND PREFER TO USE BIRTH CONTROL DEVICES (PILLS OR INTERUTERINE DEVICES) WHICH ARE NOT COITUS-CONNECTED AND ANTITHETICAL TO THEIR SEXUAL ATTITUDES AND TRADITIONS. CONTRARY TO THE BELIEF THAT THE POOR ARE LESS LIKELY TO UTILIZE EXISTING HEALTH FACILITIES OR TO TAKE PART…

  6. 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…

  7. RADAR OBSERVATION CONDITIONS OF POOR VISIBILITY,

    DTIC Science & Technology

    Ship navigational radar is an effective means for revealing above-water objects in conditions of poor visibility. A radar image of the surrounding...radar observation and with the competent operation of the set, radar is a reliable means of detection of encountered vessels in conditions of poor

  8. The Chronically Poor: Breaking the Cycle.

    ERIC Educational Resources Information Center

    Morris-Bilotti, Sharon

    This question-and-answer format paper looks at some of the basic issues surrounding the chronically poor and initiatives and services designed to break the poverty cycle. A first section explores some of the myths and realities surrounding the characteristics of the chronically poor population and notes that this population is comprised of…

  9. Cognitive Profiles of Korean Poor Readers

    ERIC Educational Resources Information Center

    Cho, Jeung-Ryeul; Ji, Yu-Kyong

    2011-01-01

    This study compared the performance of 30 poor readers in the third grade with those of 30 average readers of the same age and 30 younger readers matched with the same reading level on phonological, visuo-perceptual, orthographic, and naming speed tasks. Individual data revealed heterogeneous profiles for the poor readers: six (20%) exhibited…

  10. The Crisis of the Near Poor

    ERIC Educational Resources Information Center

    Newman, Katherine S.; Tan Chen, Victor

    2007-01-01

    This article focuses on the "missing class," the near poor whose incomes place them above the poverty line, but well below the middle class. Near-poor families with two parents and two children subsist on $20,000 to $40,000 a year, which disqualifies them for virtually all public subsidies, but is a far cry from what they need to be…

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

    PubMed

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

    2016-11-30

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

  12. Copper toxicity in the crab, Scylla serrata, copper levels in tissues and regulation after exposure to a copper-rich medium

    SciTech Connect

    Arumugam, M.; Ravindranath, M.H.

    1987-10-01

    In the decapod crustaceans copper is distributed in various tissues. In these animals the tissue copper generally exists in four forms; ionic, bound to proteins, lipids and membrane. In the estuarine crab Scylla serrata, the haemolymph copper exists only in association with proteins, whereas in the hepatopancreas it exists in all the four forms and in gills it exists in all the forms except in combination with lipids. Although food is the major source of copper in decapod crustaceans evidence indicate that copper may be directly obtained from the environment. It was postulated earlier that in Scylla serrata the haemolymph and hepatopancreas may be involved in copper regulation. In the present work the authors have studied the nature and levels of copper in different tissues after exposing the crabs to copper-rich medium. The results indicate the relative importance of various tissues in accumulation an the possible mechanisms of regulation of the environmental copper. Besides, as a pre-requisite for studies of this kind, the toxic levels for different forms of copper were estimated since the form of toxicant is known to influence the toxicity to the decapod crustaceans.

  13. 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

    2014-01-23

    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.

  14. 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

  15. Energy and minorities, women, and the poor

    SciTech Connect

    Perry, H.L.; Perry, E.B.

    1980-01-01

    A comprehensive, up-to-date (1975 to 1980) bibliography of articles, books and other publications is presented dealing with the subject of energy and minorities, women and the poor. Included are academic, popular, and government publications as well as publications by private groups and organizations. It is intended for political scientists, sociologists, economists, home economists, energy planners, energy managers and others interested in the interface of minorities, women, and the poor with energy. Following a brief introduction, there is a general listing. Also included are references dealing with energy and black Americans, native Americans (Indians), the poor, and women. (MJJ)

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

    PubMed

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

    2014-12-01

    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.

  17. Overexpression of miR-26b-5p regulates the cell cycle by targeting CCND2 in GC-2 cells under exposure to extremely low frequency electromagnetic fields.

    PubMed

    Liu, Yong; Liu, Wen-Bin; Liu, Kai-Jun; Ao, Lin; Cao, Jia; Zhong, Julia Li; Liu, Jin-Yi

    2016-01-01

    The increasing prevalence of extremely low frequency electromagnetic fields (ELF-EMFs) exposure has raised considerable public concern regarding the potential hazardous effects of ELF-EMFs on male reproductive function. Increasing evidence indicates that miRNAs are necessary for spermatogenesis and male fertility. However, the regulation of miRNA expression and the roles of miRNAs in response to ELF-EMFs remain unclear. In our study, mouse spermatocyte-derived GC-2 cells were intermittently exposed to a 50 Hz ELF-EMF for 72 h (5 min on/10 min off) at magnetic field intensities of 1 mT, 2 mT and 3 mT. MiR-26b-5p was differentially expressed in response to different magnetic field intensities of ELF-EMFs. The host gene CTDSP1 showed an unmethylation status in GC-2 cells at different magnetic field intensities of ELF-EMF exposure. MiR-26b-5p had no significant, obvious influence on the cell viability, apoptosis or cell cycle of GC-2 cells. However, the overexpression of miR-26b-5p significantly decreased the percentage of G0/G1 phase cells and slightly increased the percentage of S phase cells compared to the sham group that was exposed to a 50 Hz ELF-EMF. Computational algorithms identified Cyclin D2 (CCND2) as a direct target of miR-26b-5p. MiR-26b-5p and a 50 Hz ELF-EMF altered the expression of CCND2 at both the mRNA and protein levels. Overexpressed miR-26b-5p in GC-2 cells can change the mRNA expression of CCND2 following 50 Hz ELF-EMF at 3 mT. These findings demonstrate that miR-26b-5p could serve as a potential biomarker following 50 Hz ELF-EMF exposure, and miR-26b-5p-CCND2-mediated cell cycle regulation might play a pivotal role in the biological effects of ELF-EMFs.

  18. Overexpression of miR-26b-5p regulates the cell cycle by targeting CCND2 in GC-2 cells under exposure to extremely low frequency electromagnetic fields

    PubMed Central

    Liu, Yong; Liu, Wen-bin; Liu, Kai-jun; Ao, Lin; Cao, Jia; Zhong, Julia Li; Liu, Jin-yi

    2016-01-01

    ABSTRACT The increasing prevalence of extremely low frequency electromagnetic fields (ELF-EMFs) exposure has raised considerable public concern regarding the potential hazardous effects of ELF-EMFs on male reproductive function. Increasing evidence indicates that miRNAs are necessary for spermatogenesis and male fertility. However, the regulation of miRNA expression and the roles of miRNAs in response to ELF-EMFs remain unclear. In our study, mouse spermatocyte-derived GC-2 cells were intermittently exposed to a 50 Hz ELF-EMF for 72 h (5 min on/10 min off) at magnetic field intensities of 1 mT, 2 mT and 3 mT. MiR-26b-5p was differentially expressed in response to different magnetic field intensities of ELF-EMFs. The host gene CTDSP1 showed an unmethylation status in GC-2 cells at different magnetic field intensities of ELF-EMF exposure. MiR-26b-5p had no significant, obvious influence on the cell viability, apoptosis or cell cycle of GC-2 cells. However, the overexpression of miR-26b-5p significantly decreased the percentage of G0/G1 phase cells and slightly increased the percentage of S phase cells compared to the sham group that was exposed to a 50 Hz ELF-EMF. Computational algorithms identified Cyclin D2 (CCND2) as a direct target of miR-26b-5p. MiR-26b-5p and a 50 Hz ELF-EMF altered the expression of CCND2 at both the mRNA and protein levels. Overexpressed miR-26b-5p in GC-2 cells can change the mRNA expression of CCND2 following 50 Hz ELF-EMF at 3 mT. These findings demonstrate that miR-26b-5p could serve as a potential biomarker following 50 Hz ELF-EMF exposure, and miR-26b-5p-CCND2-mediated cell cycle regulation might play a pivotal role in the biological effects of ELF-EMFs. PMID:26637059

  19. 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.

  20. 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.

  1. 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.

  2. Market Discrimination Against the Poor and the Impact of Consumer Disclosure Laws: The Used Car Industry. Discussion Paper No. 486-78.

    ERIC Educational Resources Information Center

    McNeil, Kenneth; And Others

    The poor pay more than the non-poor for similar products in many consumer goods markets. This disparity seems not to be addressed by consumer protection regulations like disclosure laws. Several lines of argument suggest that the poor will not benefit from disclosure regulation either because they lack the ability to use information effectively…

  3. Lead exposure and heat shock inhibit cell proliferation in human HeLa and K562 cells by inducing expression and activity of the heme-regulated eIF-2alpha kinase.

    PubMed

    Sarkar, Angshuman; Chattopadhyay, Samit; Kaul, Ruchika; Pal, Jayanta K

    2002-12-01

    We have used human cell lines, namely, K562 and HeLa cells as model systems in understanding the mechanism of lead toxicity and heat shock, that may be mediated by the heme-regulated eIF-2alpha kinase which is also called the heme-regulated inhibitor (HRI). RT-PCR analysis using HRI-specific primers indicated a two- to three-fold increase in HRI expression in K562 and HeLa cells exposed to lead acetate and heat shock, respectively. Further, in vitro eIF-2alpha kinase assay indicated a two- to three-fold increase in HRI kinase activity during lead toxicity in K562 cells. This increase in HRI expression and its activity was accompanied by a significant decrease in cell proliferation and cell viability. This is therefore, the first report indicating that both heavy metal exposure and heat shock cause inhibition of protein synthesis not by activation of HRI alone but by its over-expression as well as activation. Our data indicate further that lead-induced inhibition of cell proliferation may be caused due to inhibition of protein synthesis resulted due to induced expression and activity of HRI.

  4. Acute sarin exposure causes differential regulation of choline acetyltransferase, acetylcholinesterase, and acetylcholine receptors in the central nervous system of the rat.

    PubMed

    Khan, W A; Dechkovskaia, A M; Herrick, E A; Jones, K H; Abou-Donia, M B

    2000-09-01

    Acute neurotoxic effects of sarin (O:-isopropylmethylphosphonoflouridate) in male Sprague-Dawley rats were studied. The animals were treated with intramuscular (im) injections of either 1 x LD(50) (100 microg/kg), and sacrificed at 0. 5, 1, 3, 6, 15, or 20 h after treatment, or with im injections of either 0.01, 0.1, 0.5, or 1 x LD(50) and sacrificed 15 h after treatment. Plasma butyrylcholinesterase (BChE) and brain regional acetylcholinesterase (AChE) were inhibited (45-55%) by 30 min after the LD(50) dose. BChE in the plasma and AChE in cortex, brainstem, midbrain, and cerebellum remained inhibited for up to 20 h following a single LD(50) treatment. No inhibition in plasma BChE activity was observed 20 h after treatment with doses lower than the LD(50) dose. Midbrain and brainstem seem to be most responsive to sarin treatment at lower doses, as these regions exhibited inhibition (approximately 49% and 10%, respectively) in AChE activity following 0.1 x LD(50) treatment, after 20 h. Choline acetyltransferase (ChAT) activity was increased in cortex, brainstem, and midbrain 6 h after LD(50) treatment, and the elevated enzyme activity persisted up to 20 h after treatment. Cortex ChAT activity was significantly increased following a 0.1 x LD(50) dose, whereas brainstem and midbrain did not show any effect at lower doses. Treatment with an LD(50) dose caused a biphasic response in cortical nicotinic acetylcholine receptor (nAChR) and muscarinic acetylcholine receptor (m2-mAChR) ligand binding, using [(3)H]cytisine and [(3)H]AFDX-384 as ligands for nAChR and mAChR, respectively. Decreases at 1 and 3 h and consistent increases at 6, 15, and 20 h in nAChR and m2-mAChR were observed following a single LD(50) dose. The increase in nAChR ligand binding densities was much more pronounced than in mAChR. These results suggest that a single exposure of sarin, ranging from 0.1 to 1 x LD(50), modulates the cholinergic pathways differently and thereby causes dysregulation in

  5. Pregnancy loss and eye malformations in offspring of F344 rats following gestational exposure to mixtures of regulated trihalomethanes and haloacetic acids.

    PubMed

    Narotsky, Michael G; Best, Deborah S; McDonald, Anthony; Godin, Elizabeth A; Hunter, E Sidney; Simmons, Jane Ellen

    2011-01-01

    Chlorination of drinking water yields hundreds of disinfection by-products (DBPs). Among the DBPs, four trihalomethanes (THMs; chloroform, bromodichloromethane, chlorodibromomethane, bromoform) and five haloacetic acids (HAAs; chloroacetic, dichloroacetic, trichloroacetic, bromoacetic, and dibromoacetic acid) are U.S. EPA regulated. We assessed the combined toxicity of these DBPs. F344 rats were treated with mixtures of the four THMs (THM4), the five HAAs (HAA5), or nine DBPs (DBP9; THM4+HAA5). Mixtures were administered in 10% Alkamuls(®) EL-620 daily by gavage on gestation days 6-20. Litters were examined postnatally. All three mixtures caused pregnancy loss at ≥ 613 μmol/kg/day. In surviving litters, resorption rates were increased in groups receiving HAA5 at 615 μmol/kg/day and DBP9 at 307 μmol/kg/day. HAA5 caused eye malformations (anophthalmia, microphthalmia) at ≥ 308 μmol/kg/day. Thus, both HAAs and THMs contributed to DBP9-induced pregnancy loss. The presence of THMs in the full mixture, however, appeared to reduce the incidence of HAA-induced eye defects.

  6. 7 CFR 51.1166 - Poorly colored.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 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... percent of the surface may be solid dark green color....

  7. 7 CFR 51.1166 - Poorly colored.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 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... percent of the surface may be solid dark green color....

  8. Exposure to bushfire smoke during prescribed burns and wildfires: firefighters' exposure risks and options.

    PubMed

    Reisen, Fabienne; Hansen, Dane; Meyer, C P Mick

    2011-02-01

    Firefighters are exposed to known health-damaging air pollutants present in bushfire smoke and poorly managed exposure can result in serious health issues. A better understanding of exposure levels and the major factors influencing exposures is crucial for the development of mitigation strategies to minimise exposure risks and adverse health impacts. This study monitored air toxics within the breathing zone of firefighters at prescribed burns and at wildfires in Australia. The results showed that exposure levels were highly variable, with higher exposures (sometimes exceeding occupational exposure standards) associated with particular work tasks (such as patrol and suppression) and with certain burn conditions. The majority of firefighter's exposures were at low and moderate levels (~60%), however considerable attention should be given to the high (~30%) and very high (6%) exposure risk situations for which acute and chronic health risks are very likely and for which control strategies should be developed and implemented to minimise health risks.

  9. Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators.

    PubMed

    Ramírez-López, María T; Arco, Rocío; Decara, Juan; Vázquez, Mariam; Rivera, Patricia; Blanco, Rosario Noemi; Alén, Francisco; Gómez de Heras, Raquel; Suárez, Juan; Rodríguez de Fonseca, Fernando

    2016-01-01

    Maternal malnutrition causes long-lasting alterations in feeding behavior and energy homeostasis in offspring. It is still unknown whether both, the endocannabinoid (eCB) machinery and the lipid metabolism are implicated in long-term adaptive responses to fetal reprogramming caused by maternal undernutrition. We investigated the long-term effects of maternal exposure to a 20% standard diet restriction during preconceptional and gestational periods on the metabolically-relevant tissues hypothalamus, liver, and perirenal fat (PAT) of male and female offspring at adulthood. The adult male offspring from calorie-restricted dams (RC males) exhibited a differential response to the CB1 antagonist AM251 in a chocolate preference test as well as increased body weight, perirenal adiposity, and plasma levels of triglycerides, LDL, VLDL, bilirubin, and leptin. The gene expression of the cannabinoid receptors Cnr1 and Cnr2 was increased in RC male hypothalamus, but a down-expression of most eCBs-metabolizing enzymes (Faah, Daglα, Daglβ, Mgll) and several key regulators of fatty-acid β-oxidation (Cpt1b, Acox1), mitochondrial respiration (Cox4i1), and lipid flux (Pparγ) was found in their PAT. The female offspring from calorie-restricted dams exhibited higher plasma levels of LDL and glucose as well as a reduction in chocolate and caloric intake at post-weaning periods in the feeding tests. Their liver showed a decreased gene expression of Cnr1, Pparα, Pparγ, the eCBs-degrading enzymes Faah and Mgll, the de novo lipogenic enzymes Acaca and Fasn, and the liver-specific cholesterol biosynthesis regulators Insig1 and Hmgcr. Our results suggest that the long-lasting adaptive responses to maternal caloric restriction affected cannabinoid-regulated mechanisms involved in feeding behavior, adipose β-oxidation, and hepatic lipid and cholesterol biosynthesis in a sex-dependent manner.

  10. Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators

    PubMed Central

    Ramírez-López, María T.; Arco, Rocío; Decara, Juan; Vázquez, Mariam; Rivera, Patricia; Blanco, Rosario Noemi; Alén, Francisco; Gómez de Heras, Raquel; Suárez, Juan; Rodríguez de Fonseca, Fernando

    2016-01-01

    Maternal malnutrition causes long-lasting alterations in feeding behavior and energy homeostasis in offspring. It is still unknown whether both, the endocannabinoid (eCB) machinery and the lipid metabolism are implicated in long-term adaptive responses to fetal reprogramming caused by maternal undernutrition. We investigated the long-term effects of maternal exposure to a 20% standard diet restriction during preconceptional and gestational periods on the metabolically-relevant tissues hypothalamus, liver, and perirenal fat (PAT) of male and female offspring at adulthood. The adult male offspring from calorie-restricted dams (RC males) exhibited a differential response to the CB1 antagonist AM251 in a chocolate preference test as well as increased body weight, perirenal adiposity, and plasma levels of triglycerides, LDL, VLDL, bilirubin, and leptin. The gene expression of the cannabinoid receptors Cnr1 and Cnr2 was increased in RC male hypothalamus, but a down-expression of most eCBs-metabolizing enzymes (Faah, Daglα, Daglβ, Mgll) and several key regulators of fatty-acid β-oxidation (Cpt1b, Acox1), mitochondrial respiration (Cox4i1), and lipid flux (Pparγ) was found in their PAT. The female offspring from calorie-restricted dams exhibited higher plasma levels of LDL and glucose as well as a reduction in chocolate and caloric intake at post-weaning periods in the feeding tests. Their liver showed a decreased gene expression of Cnr1, Pparα, Pparγ, the eCBs-degrading enzymes Faah and Mgll, the de novo lipogenic enzymes Acaca and Fasn, and the liver-specific cholesterol biosynthesis regulators Insig1 and Hmgcr. Our results suggest that the long-lasting adaptive responses to maternal caloric restriction affected cannabinoid-regulated mechanisms involved in feeding behavior, adipose β-oxidation, and hepatic lipid and cholesterol biosynthesis in a sex-dependent manner. PMID:28082878

  11. Transcriptional regulation of two RTE-like genes of carnation during flower senescence and upon ethylene exposure, wounding treatment and sucrose supply.

    PubMed

    Yu, Y; Wang, H; Liu, J; Fu, Z; Wang, J; Liu, J

    2011-09-01

    RTE1 (REVERSION-TO-ETHYLENE SENSITIVITY1) was identified as a positive regulator of ETR1 (ethylene resistant1) function in Arabidopsis; RTEs are a small gene family. Ethylene plays a crucial role in the senescence of carnation (Dianthus caryophyllus L.) flowers. Two cDNA clones encoding putative RTE-like protein (DCRTE1 and DCRTH1) were obtained from total RNA isolated from senescing carnation petals using RT-PCR and RACE techniques. The predicted proteins of DCRTE1 and DCRTH1 consist of 228 and 233 amino acids, respectively. Interestingly, the deduced DCRTE1 protein, like most other RTEs, includes two putative transmembrane domains, while the deduced DCRTH1 protein includes five putative transmembrane domains, according to the TMHMM database. Northern blots showed that the level of DCRTE1 mRNA in petals first decreased then increased remarkably after ethylene production started, and DCRTE1 expression showed an increasing trend in ovaries during natural flower senescence. The amount of DCRTH1 transcripts increased gradually in both petals and ovaries during natural senescence. Exogenous ethylene increased transcript abundance of DCRTE1 and DCRTH1 to various degrees in both petals and ovaries. STS treatment decreased the level of DCRTH1 mRNA in petals and ovaries compared with the control. DCRTE1 and DCRTH1 showed a rapid increase and then a decrease in mRNA accumulation in leaves after wounding. These results suggest that both DCRTE1 and DCRTH1 could play important roles in flower senescence-related signalling. Sucrose treatment did not remarkably affect the amount of DCRTE1 and DCRTH1 mRNAs.

  12. Cyclic diGMP regulates production of sortase substrates of Clostridium difficile and their surface exposure through ZmpI protease-mediated cleavage.

    PubMed

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

    2015-10-02

    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.

  13. 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…

  14. 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 ...

  15. Is American business working for the poor?

    PubMed

    Bane, M J; Ellwood, D T

    1991-01-01

    At first glance, poverty seems to have little to do with business. When most people--managers included--think about poverty, they assume that people are poor because they are isolated from the mainstream economy, not productive participants in it. But according to Harvard University professors Mary Jo Bane and David Ellwood, this is a misleading image of the true face of poverty in the United States today. Most poor adults--and a full 90% of poor children--live in families where work is the norm, not the exception. Poor people often work or want to work. But at the low-wage end of the American economy, having a job is no guarantee of avoiding poverty. Poverty is a business issue, then, because the American poor are part of the American work force. And this poses a problem for managers. In a more competitive and fast-changing economic environment, the performance of companies increasingly depends on the capabilities of their employees. In response to this human-resource challenge, more and more managers are embracing the language of "empowerment". And yet how can low-wage employees believe empowerment when their experience of work is, quite literally, impoverishment? It is unlikely that American companies can create the work force of the future with the poverty policies of the past. Fortunately, there are some simple policy mechanisms that can assist the working poor without putting an undue burden on business. Enacting them, however, requires managers to see poverty policy as one part of a national human-resource strategy that links the strategic concerns of companies to a broad social agenda.

  16. 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…

  17. 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.

  18. NCAM regulates cell motility.

    PubMed

    Prag, Søren; Lepekhin, Eugene A; Kolkova, Kateryna; Hartmann-Petersen, Rasmus; Kawa, Anna; Walmod, Peter S; Belman, Vadym; Gallagher, Helen C; Berezin, Vladimir; Bock, Elisabeth; Pedersen, Nina

    2002-01-15

    Cell migration is required during development of the nervous system. The regulatory mechanisms for this process, however, are poorly elucidated. We show here that expression of or exposure to the neural cell adhesion molecule (NCAM) strongly affected the motile behaviour of glioma cells independently of homophilic NCAM interactions. Expression of the transmembrane 140 kDa isoform of NCAM (NCAM-140) caused a significant reduction in cellular motility, probably through interference with factors regulating cellular attachment, as NCAM-140-expressing cells exhibited a decreased attachment to a fibronectin substratum compared with NCAM-negative cells. Ectopic expression of the cytoplasmic part of NCAM-140 also inhibited cell motility, presumably via the non-receptor tyrosine kinase p59(fyn) with which NCAM-140 interacts. Furthermore, we showed that the extracellular part of NCAM acted as a paracrine inhibitor of NCAM-negative cell locomotion through a heterophilic interaction with a cell-surface receptor. As we showed that the two N-terminal immunoglobulin modules of NCAM, which are known to bind to heparin, were responsible for this inhibition, we presume that this receptor is a heparan sulfate proteoglycan. A model for the inhibitory effect of NCAM is proposed, which involves competition between NCAM and extracellular components for the binding to membrane-associated heparan sulfate proteoglycan.

  19. Issues in medical exposures.

    PubMed

    Elliott, Alex

    2009-06-01

    Medical exposures account, on average, for some 14% of the background ionising radiation exposure in the UK and form the great majority of the non-natural component. In the United States of America, medical exposures comprised over 50% of the total in 2006. This is due primarily to an increase in x-ray computed tomography (CT) and positron emission tomography (PET) procedures. This paper highlights the potential problems in the use of CT scanning to investigate the asymptomatic individual, where the traditional risk/benefit considerations are less clear-cut than in conventional clinical situations. It draws on a recent COMARE report which examined the use of CT for whole body, heart, lung and colon studies. The number of PET facilities is increasing rapidly in the UK and, in addition to considerations of radiation dose to subjects, careful planning is necessary to limit doses to staff. In non-ionising radiation, a topic of keen interest at present is the use of increasingly powerful sunbeds, particularly by those aged under 18. Legislation and regulation vary widely across Europe and the Scottish Parliament has recently introduced the first UK regulation. It is suggested that further research is required into the effects of current UV systems and the reasons why tanning is thought so desirable by Caucasians. Lastly, a number of issues requiring radiobiological and epidemiological input are considered and actions to satisfy these identified.

  20. Coping with poor water supplies: empirical evidence from Kathmandu, Nepal.

    PubMed

    Katuwal, Hari; Bohara, Alok K

    2011-03-01

    The authors examined the demand for clean drinking water using treatment behaviors in Kathmandu, Nepal. Water supply is inadequate, unreliable and low quality. Households engage in several strategies to cope with the unreliable and poor quality of water supplies. Some of the major coping strategies are hauling, storing, and point-of-use treatment. Boiling, filtering, and use of Uro-guard are some of the major treatment methods. Using Water Survey of Kathmandu, the authors estimated the effect of wealth, education, information, gender, caste/ethnicity and opinion about water quality on drinking water treatment behaviors. The results show that people tend to increase boiling and then filtering instead of only one method if they are wealthier. In addition, people boil and then filter instead of boiling only and filtering only if they think that water delivered to the tap is dirty. Exposure to information has the strongest effect in general for the selection of all available treatment modes.

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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…

  6. COMPREHENSIVE HEALTH SERVICES FOR THE RURAL POOR.

    ERIC Educational Resources Information Center

    LOGSDON, DONALD N.

    SEVERAL WRITERS HAVE DEPICTED AGRICULTURAL MIGRANTS AS BEING ONE OF THE MOST DEPRIVED GROUPS IN OUR COUNTRY. HOWEVER, THE NON-MIGRANT AGRICULTURAL WORKERS, WHO FAR OUTNUMBER THE MIGRANTS, ALSO LIVE IN EXTREMELY POOR CIRCUMSTANCES AND ARE VIRTUALLY UNNOTICED BECAUSE THEY DO NOT DRAW ATTENTION THROUGH MIGRATION. BOTH OF THESE GROUPS ARE IN DIRE NEED…

  7. 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.

  8. Resilient Learners in Schools Serving Poor Communities

    ERIC Educational Resources Information Center

    Frempong, G.; Visser, M.; Feza, Nosisi; Winnaar, L.; Nuamah, S.

    2016-01-01

    Introduction: Through the education for all initiative, a number of education systems have been able to provide access to their students at the basic education level. The major challenge is that most of these learners, especially, those from poor families who attend schools with limited resources are often not successful. However, in South Africa,…

  9. 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…

  10. 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…

  11. 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…

  12. 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.

    PubMed

    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™). In both systems, administration of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide (CEES, 100-1000μM) 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-β-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.

  13. 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.

  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

    PubMed Central

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

    2012-01-01

    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-FTTM). In both systems, administration of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide (CEES, 100–1000 µM) 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-β-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. PMID:21457723

  15. 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

  16. 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...

  17. 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...

  18. 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...

  19. 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... 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...

  20. 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...

  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. 12 CFR 217.53 - Equity exposures to investment funds.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... (3) If an equity exposure to an investment fund is part of a hedge pair and the Board-regulated... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Equity exposures to investment funds. 217.53... Assets for Equity Exposures § 217.53 Equity exposures to investment funds. (a) Available approaches....

  3. 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.

  4. 7 CFR 51.1166 - Poorly colored.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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... applied to common oranges means that not more than 25 percent of the surface may be solid dark green color....

  5. 7 CFR 51.779 - Poorly colored.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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....

  6. 7 CFR 51.779 - Poorly colored.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 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....

  7. 7 CFR 51.1166 - Poorly colored.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 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... applied to common oranges means that not more than 25 percent of the surface may be solid dark green color....

  8. 7 CFR 51.1166 - 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... applied to common oranges means that not more than 25 percent of the surface may be solid dark green color....

  9. 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....

  10. 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

  11. 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…

  12. 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…

  13. Online and offline inferential and textual processing of poor comprehenders: Evidence from a probing method.

    PubMed

    Yeari, Menahem; Elentok, Shiri; Schiff, Rachel

    2017-03-01

    Numerous studies have demonstrated that poor inferential processing underlies the specific deficit of poor comprehenders. However, it is still not clear why poor comprehenders have difficulties in generating inferences while reading and whether this impairment is general or specific to one or more types of inferences. The current study employed an online probing method to examine the spontaneous immediate activation of two inference types-forward-predictive inferences and backward-explanatory inferences-during reading. In addition, we examined the ability of poor comprehenders to retain, suppress, and reactivate text information (relevant for inferencing) in working memory. The participants, 10- to 12-year-old good and poor comprehenders, read short narratives and name inference or text word probes following a predictive, intervening, or bridging sentence. Comparing the size of probe-naming facilitations revealed that poor comprehenders generate predictive inferences, albeit more slowly than good comprehenders, and generate explanatory inferences to a lesser extent than good comprehenders. Moreover, we found that this inferior inferential processing is presumably a result of poor retention and reactivation of inference-evoking text information during reading. Finally, poorer reading comprehension was associated with higher activation of information when it was less relevant following the intervening sentences. Taken together, the current findings demonstrate the manner in which poor regulation of relevant and less relevant information during reading underlies the specific comprehension difficulties experienced by poor comprehenders.

  14. Prenatal cigarette exposure and infant learning stimulation as predictors of cognitive control in childhood

    PubMed Central

    Mezzacappa, Enrico; Buckner, John C.; Earls, Felton

    2010-01-01

    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 if not greater in magnitude to 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

  15. Dilemma continues for resource-poor women.

    PubMed

    Denoon, D J

    1999-09-06

    This article presents the resource-poor women facing a difficult dilemma of making choices regarding breast-feeding. Findings showed that there were 1600 perinatal HIV infections in resource-poor settings such as sub-Saharan Africa. Even prior to zidovudine interventions, a doubling HIV infection risk was found in both HIV-exposed and breast-fed infants, particularly in the first 5 months after birth. Because of these findings, the WHO recommends voluntary HIV testing and counseling for all pregnant women. A study documents that a neonate with nevirapine treatment was found to reduce transmission to about 50%. Further research is needed on infectious unit in breast milk, role of host immunity and genetics, identification of protective factors in breast milk and factors affecting HIV viral load, breast conditions and breast milk substitutes.

  16. Enhancement of imagery in poor visibility conditions

    NASA Astrophysics Data System (ADS)

    Woodell, Glenn; Jobson, Daniel J.; Rahman, Zia-ur; Hines, Glenn

    2005-05-01

    Current still image and video systems are typically of limited use in poor visibility conditions such as in rain, fog, smoke, and haze. These conditions severely limit the range and effectiveness of imaging systems because of the severe reduction in contrast. The NASA Langley Research Center"s Visual Information Processing Group has developed an image enhancement technology based on the concept of a visual servo that has direct applications to the problem of poor visibility conditions. This technology has been used in cases of severe image turbidity in air as well as underwater with dramatic results. Use of this technology could result in greatly improved performance of perimeter surveillance systems, military, security, and law enforcement operations, port security, both on land and below water, and air and sea rescue services, resulting in improved public safety.

  17. 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…

  18. Health practices of the elderly poor.

    PubMed Central

    Lubben, J E; Weiler, P G; Chi, I

    1989-01-01

    The purpose of the present study was to describe the health practices of the elderly poor and to examine the association between specific health practices and subsequent hospital use. Data came from a sample of 931 Medicaid elderly living in California. Smoking, limited social networks, and lack of regular exercise significantly increased the odds of subsequent hospital utilization. Implications of these findings, which could benefit health promotion intervention and treatment programs for the elderly, were discussed. PMID:2658629

  19. Poorly differentiated (anaplastic) seminoma of the testis.

    PubMed

    Cockburn, A G; Vugrin, D; Batata, M; Hajdu, S; Whitmore, W F

    1984-05-01

    Anaplastic seminoma constitutes approximately 17% of total experience with seminoma at Memorial Sloan-Kettering Cancer Center. Among 25 previously untreated patients, 11 (44%) were clinical Stage I, and 14 (56%) were clinical Stage II or III. Treatment of these 25 patients with the same regimens employed for classical seminoma yielded an overall 80% 5-year apparent cure rate. Survival rates were poor in eight previously treated patients referred with recurrence.

  20. Criminal exposure.

    PubMed

    1999-09-03

    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.

  1. Occupational exposure to wood dust in the british woodworking industry in 1999/2000.

    PubMed

    Black, Nigel; Dilworth, Martin; Summers, Nick

    2007-04-01

    Exposure to inhalable wood dust and compliance with the British Control of Substances Hazardous to Health (COSHH) Regulations 1999 were assessed at a representative cross-section of the British woodworking industry. Median exposures ranged from 1.5 to 2.8 mg/m(3) across the selected industry groups, the lowest being in sawmilling and planing of wood. Overall, 27% of values exceeded the maximum exposure limit (MEL) at that time of 5 mg/m(3). These results showed that the percentage of exposures above the MEL was less than in a survey carried out 10 years earlier. A wide variation of exposures was identified at different machines and tasks. At least 90% at bandsawing and cross-cut sawing were <5 mg/m(3). In contrast, dust emission at circular sawing, sanding, cleaning and a miscellaneous group of activities was poorly controlled. Between 32 and 50% of results from these categories exceeded 5 mg/m(3). The lower exposures in sawmills were largely attributable to the low usage of sanders and a group of circular saws, to the high use of bandsaws and moulders and to coarser dust from undried timber. Compliance with the COSHH Regulations was inadequate. Companies that claimed to have some form of written COSHH assessment were generally no more effective at controlling exposure to dust than those without an assessment. Similarly the ability of premises that provided information, instruction and training on the risks to health from wood dust and on measures to prevent or control those risks was not generally greater than in those that did not. Maintenance of local exhaust ventilation systems emerged as essential for achieving good control. Companies that followed both the statutory 14-monthly thorough examination and testing schedule and a weekly check system were more successful in this respect than those that did not. In spite of this, local exhaust ventilation alone provided insufficient dust control at several woodworking activities.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. A 'Scottish Poor Law of Lunacy'? Poor Law, Lunacy Law and Scotland's parochial asylums.

    PubMed

    Farquharson, Lauren

    2017-03-01

    Scotland's parochial asylums are unfamiliar institutional spaces. Representing the concrete manifestation of the collision between two spheres of legislation, the Poor Law and the Lunacy Law, six such asylums were constructed in the latter half of the nineteenth century. These sites expressed the enduring mandate of the Scottish Poor Law 1845 over the domain of 'madness'. They were institutions whose very existence was fashioned at the directive of the local arm of the Poor Law, the parochial board, and they constituted a continuing 'Scottish Poor Law of Lunacy'. Their origins and operation significantly subverted the intentions and objectives of the Lunacy Act 1857, the aim of which had been to institute a public district asylum network with nationwide coverage.

  7. 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

  8. 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.

  9. 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

  10. Associations among plasma metabolite levels and short-term exposure to PM2.5 and ozone in a cardiac catheterization cohort.

    EPA Science Inventory

    RATIONALE: Exposure to ambient particulate matter (PM) and ozone has been associated with cardiovascular disease (CVD). However, the mechanisms linking PM and ozone exposure to CVD remain poorly understood .OBJECTIVE: This study explored associations between short-term exposures ...

  11. Oxygen Abundances in Metal-Poor Stars

    NASA Astrophysics Data System (ADS)

    Fulbright, J. P.

    1999-05-01

    The oxygen abundances of metal-poor late-type stars can be obtained by one four methods: 1) the [O I] forbidden lines at 6300 and 6363 Angstroms, 2) the O I triplet at 7774 Angstroms, 3) OH lines at 3100-3150 Angstroms, and 4) IR CO and OH bands. Each of these methods have their strengths and weaknesses, and finding common agreement between the methods has sometimes been elusive. Recently two groups (Israelian et al, 1998, ApJ, 507, 805 and Boesgaard et al, 1999, AJ, 117, 492) have presented results from the UV OH lines and the O I triplet that suggest that the [O/Fe]-ratio continues to increase as [Fe/H] decreases. This differs from the 'traditional' result that held that [O/Fe] plateaus at +0.5 as [Fe/H] decreases. Conversely, Fulbright and Kraft (AJ, July 1999) show that in two very metal-poor stars the [O I] 6300 Angstroms line gives abundances 0.5 dex lower than obtained in the above studies. In this talk, I hope to discuss these papers and speculate on potental causes to the discrepency.

  12. Melt extrusion with poorly soluble drugs.

    PubMed

    Shah, Sejal; Maddineni, Sindhuri; Lu, Jiannan; Repka, Michael A

    2013-08-30

    Melt extrusion (ME) over recent years has found widespread application as a viable drug delivery option in the drug development process. ME applications include taste masking, solid-state stability enhancement, sustained drug release and solubility enhancement. While ME can result in amorphous or crystalline solid dispersions depending upon several factors, solubility enhancement applications are centered around generating amorphous dispersions, primarily because of the free energy benefits they offer. In line with the purview of the current issue, this review assesses the utility of ME as a means of enhancing solubility of poorly soluble drugs/chemicals. The review describes major processing aspects of ME technology, definition and understanding of the amorphous state, manufacturability, analytical characterization and biopharmaceutical performance testing to better understand the strength and weakness of this formulation strategy for poorly soluble drugs. In addition, this paper highlights the potential advantages of employing a fusion of techniques, including pharmaceutical co-crystals and spray drying/solvent evaporation, facilitating the design of formulations of API exhibiting specific physico-chemical characteristics. Finally, the review presents some successful case studies of commercialized ME based products.

  13. How poor are women in rural India?

    PubMed

    Rajuladevi, A K

    1992-07-01

    The assessment of poor women in India as dependent and exploited regardless of poverty focused strategies is reflected in this review of relevant literature. The scholarly approaches to the problems of poor women involve redirection and expansion of resources to women (increase bank credit) through policy and institutional changes, and involve improving women's welfare through changes in class and gender hierarchies; both pertain to restructuring power groups. A little ascribed to belief is that the organization of women's numbers will empower women; the constraints are stated. There is also some argument over whether to design women-specific programs or integrate women into existing programs; some examples are given of successes and difficulties. The regionalization of poverty in eastern and central India is discussed. The growth of the poor has been among the landless, wage-dependent households. 9.6% of households (7.5 million) are headed by women. Women work fewer hours and at lower wage scales and have fewer employment opportunities. Lower earnings are coupled with differentials in demand for female and male labor in agriculture and a crowded labor market. There is a concentration of women in less visible, nonmonetary subsistence production and domestic work. Women are undercounted in employment studies. Women predominate in agricultural activity. Women's status is influenced by economic status, caste, and ethnic background. Domestic work increases status for women and households. The poorer households have greater labor force participation, particularly as wage laborers rather than unpaid family workers. Regional factors affecting rural household strategies are factors affecting the economy (topography, rainfall, climate) and the degree of development, plus sociocultural variables (kinship and religious beliefs which affect the social domain of women), and the degree of dependence on hired vs. family labor. There are sharp contrasts in the value and survival

  14. 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.

  15. 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.

  16. Periodontal disease and poor obstetrical outcome.

    PubMed

    Carta, G; Persia, G; Falciglia, K; Iovenitti, P

    2004-01-01

    Maternal infective processes sustained especially by Gram-negative anaerobic bacteria like periodontal disease, during pregnancy, have been demonstrated to perturb the physiologic course of parturition through inflammatory cytokine production, sometimes resulting in preterm labor, preterm premature rupture of membranes and preterm low birth weight. In a matched case-control study, the hypothesis that poor oral health of pregnant women is a risk factor for low birth weight (LBW) was evaluated. Gingival crevicular fluid levels of PGE2 and IL-1beta were measured in order to determine whether mediator levels were related to current pregnancy outcome. Results indicate that GCF-PGE2 and GCF-IL-1beta levels are significantly higher in preterm low birth weight (PLBW) mothers as compared with normal birth weight controls. The data confirm that there is a possible correlation between periodontal problems typical of pregnancy and the occurrence of complications such as preterm low birth weight.

  17. Pfizer donates drug to South Africa's poor.

    PubMed

    This article reports on Pfizer's AIDS drug donation to South Africa. The donated drug, Diflucan, treats cryptococcal meningitis, a lethal brain infection that occurs in one out of 10 HIV patients. Its daily dose in South Africa costs about US$15, far more than poor people can afford. The HIV and AIDS Treatment Action Campaign, an advocacy group, had lobbied New York-based Pfizer for a year to reduce the drug's price. The donation offered hope among activists that other pharmaceutical companies would follow suit and offer HIV- and AIDS-related drugs at a discount or for free. After the announcement of the donation, the group is now lobbying Glaxo Wellcome, maker of Zidovudine. The group is asking to make the drug available for free to reduce the risk of vertical transmission. Glaxo Wellcome, however, has no plans of offering Zidovudine for free, although the drug was offered 75% cheaper in developing nations.

  18. "Managing" the poor: neoliberalism, Medicaid HMOs and the triumph of consumerism among the poor.

    PubMed

    Maskovsky, J

    2000-10-01

    In order to explore the contradictions of neoliberal health policy, this article examines Medicaid managed care in Philadelphia. At the federal and state levels, government is increasingly promoting private-sector market-based strategies over policies formerly associated with the welfare state, arguing that the former are the most effective means of achieving economic growth and guaranteeing social welfare. A prime example of this shift, Medicaid managed care is a policy by which states contract with private-sector health maintenance organizations to provide health coverage to the poor. Drawing on ethnographic and historical data, this paper shows how Pennsylvania's Medicaid managed care program has created access barriers for poor Philadelphians. It also illustrates how ideologies that justify this policy shift serve to mask its detrimental effects on the poor. By contrasting the state's consumerist model with one group's protest efforts, this article calls into question the neoliberal ideology that undergirds health and welfare "reform."

  19. 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.

  20. A global perspective on the influence of environmental exposures on the nervous system

    PubMed Central

    Tshala-Katumbay, Desire; Mwanza, Jean-Claude; Rohlman, Diane S.; Maestre, Gladys; Oriá, Reinaldo B.

    2016-01-01

    Economic and social 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 both 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 such as 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

  1. 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.

  2. Environmental source of arsenic exposure.

    PubMed

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-09-01

    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.

  3. 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

  4. RNASeq in C. elegans following manganese exposure

    PubMed Central

    Parmalee, Nancy L.; Maqbool, Shahina B.; Ye, Bin; Calder, Brent; Bowman, Aaron B.; Aschner, Michael

    2015-01-01

    Manganese is a metal that is required for optimal biological functioning of organisms. Absorption, cellular import and export, and excretion of manganese are all tightly regulated. While some genes involved in regulation, such as DMT-1 and ferroportin are known, it is presumed that many more are involved and as yet unknown. Excessive exposure to manganese, usually in industrial settings, such as mining or welding, can lead to neurotoxicity and a condition known as manganism that closely resembles Parkinson's disease. Elucidating transcriptional changes following manganese exposure could lead to the development of biomarkers for exposure. This unit presents a protocol for RNA sequencing in the worm Caenorhabditis elegans to assay for transcriptional changes following exposure to manganese. This protocol is adaptable to any environmental exposure in C. elegans. The protocol results in counts of gene transcripts in control versus exposed conditions, and a ranked list of differentially expressed genes for further study. PMID:26250396

  5. 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

  6. Pulsating Blue Metal-poor Stars

    NASA Astrophysics Data System (ADS)

    Preston, George W.; Landolt, Arlo U.

    1999-12-01

    The blue metal-poor (BMP) star CS 22966-043 is an SX Phoenicis star and the primary of a spectroscopic binary with a provisional orbital period of ~430 days. Radial velocity and UBV photometric observations of this star made in 1998 require downward revision of the orbital period to 319 days. The BMP star CS 29499-057 also appears to be an SX Phoenicis star with small amplitude (ΔV~0.04 mag) and short period (P=0.0417 days), on the basis of photometric and radial velocity observations obtained in 1998. There is some indication that it too may be the primary of a spectroscopic binary. Three other BMP stars have radial velocity standard deviations greater than those of 17 BMP radial velocity standards. We suggest that they may be small-amplitude SX Phoenicis stars. Finally, the BMP star CS 29497-017 is shown to be a short-period velocity variable (P=0.302 days) on the basis of observations accumulated over an interval of 2200 days, but we were unable to detect a light variation in 1998 July. Therefore, the nature of the velocity variation of this object remains uncertain.

  7. Poor oral health and coronary heart disease.

    PubMed

    Joshipura, K J; Rimm, E B; Douglass, C W; Trichopoulos, D; Ascherio, A; Willett, W C

    1996-09-01

    A few recent studies have shown associations between poor oral health and coronary heart disease (CHD). The objective of this study was to examine the incidence of CHD in relation to number of teeth present and periodontal disease, and to explore potential mediators of this association, in a prospective cohort study. This study is a part of the ongoing Health Professionals Follow-Up Study (HPFS). Participants included a US national sample of 44,119 male health professionals (58% of whom were dentists), from 40 to 75 years of age, who reported no diagnosed CHD, cancer, or diabetes at baseline. We recorded 757 incident cases of CHD, including fatal and non-fatal myocardial infarction and sudden death, in six years of follow-up. Among men who reported pre-existing periodontal disease, those with 10 or fewer teeth were at increased risk of CHD compared with men with 25 or more teeth (relative risk = 1.67; 95% confidence interval, 1.03 to 2.71), after adjustment for standard CHD risk factors. Among men without pre-existing periodontal disease, no relationship was found (relative risk = 1.11; 95% confidence interval, 0.74 to 1.68). The associations were only slightly attenuated after we controlled for dietary factors. No overall associations were found between periodontal disease and coronary heart disease. Tooth loss may be associated with increased risk of CHD, primarily among those with a positive periodontal disease history; diet was only a small mediator of this association.

  8. [Infant botulism after honey exposure].

    PubMed

    Godart, V; Dan, B; Mascart, G; Fikri, Y; Dierick, K; Lepage, P

    2014-06-01

    Infant botulism is a rare neuroparalytic disease caused by the neurotoxin of Clostridium botulinum. Initial clinical features are constipation, poor feeding, descending hypotonia, drooling, irritability, weak crying and cranial nerve dysfunctions. We describe the clinical progression and the epidemiological investigation carried out in a 3-month-old infant. Better knowledge of the disease should allow faster diagnosis and adequate management. We emphasize the risks associated with honey exposure in children less than one year old and that honey should not be fed to infants under 12 months of age.

  9. Cardiovascular responses to cold exposure.

    PubMed

    Sun, Zhongjie

    2010-01-01

    The prevalence of hypertension is increased in winter and in cold regions of the world. Cold temperatures make hypertension worse and trigger cardiovascular complications (stroke, myocardial infarction, heart failure, etc.). Chronic or intermittent exposure to cold causes hypertension and cardiac hypertrophy in animals. The purpose of this review is to provide the recent advances in the mechanistic investigation of cold-induced hypertension (CIH). Cold temperatures increase the activities of the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS). The SNS initiates CIH via the RAS. Cold exposure suppresses the expression of eNOS and formation of NO, increases the production of endothelin-1 (ET-1), up-regulates ETA receptors, but down-regulates ETB receptors. The roles of these factors and their relations in CIH will be reviewed.

  10. Cardiovascular responses to cold exposure

    PubMed Central

    Sun, Zhongjie

    2010-01-01

    The prevalence of hypertension is increased in winter and in cold regions of the world. Cold temperatures make hypertension worse and trigger cardiovascular complications (stroke, myocardial infarction, heart failure, etc.). Chronic or intermittent exposure to cold causes hypertension and cardiac hypertrophy in animals. The purpose of this review is to provide the recent advances in the mechanistic investigation of cold-induced hypertension (CIH). Cold temperatures increase the activities of the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS). The SNS initiates CIH via the RAS. Cold exposure suppresses the expression of eNOS and formation of NO, increases the production of endothelin-1 (ET-1), up-regulates ETA receptors, but down-regulates ETB receptors. The roles of these factors and their relations in CIH will be reviewed. PMID:20036896

  11. 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

  12. 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...

  13. 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...

  14. Electromagnetic irradiation exposure and its bioindication--an overview.

    PubMed

    Hänninen, Osmo; Huttunen, Paavo; Ekman, Reijo

    2011-01-01

    Man made electromagnetic irradiation and fields cover now the globe due to the recent extensive propagation of mobile telephony. The increased load affects animals and also plants. Especially birds have been studied. Humans are also sensitive. They are good bioindicators as epidemiological methods are available. Humans can also report symptoms which cannot be directly measured with presently available technologies. The nonionizing irradiation can as the ionizing one break the DNA, damage proteins, even increase the blood brain barrier permeability, disturb the night rest, cause fatigue and hormonal disturbances. An increase of the tumours of human head has been described in correlation with the long-term mobile phone use and on that side more exposed. The regulations covering mobile telephony are already about two decades old and need re-evaluation. The multitude of irradiation and the interaction of the different wavelength exposures, i.e., frequency sensitivity is poorly known at present. We should not forget the comparative studies of different species especially those which rely in their lives on electromagnetic orientation physiology. Some countries have issued warnings on the exposures of children. The producers of mobile technology have recently warned the users not to keep those devices in active stage in skin contact.

  15. Testing Metal-Poor Stellar Models and Isochrones with HST Parallaxes of Metal-Poor Stars

    NASA Astrophysics Data System (ADS)

    Chaboyer, B.; McArthur, B. E.; O’Malley, E.; Benedict, G. F.; Feiden, G. A.; Harrison, T. E.; McWilliam, A.; Nelan, E. P.; Patterson, R. J.; Sarajedini, A.

    2017-02-01

    Hubble Space Telescope (HST) fine guidance sensor observations were used to obtain parallaxes of eight metal-poor ([Fe/H] < ‑1.4) stars. The parallaxes of these stars determined by the new Hipparcos reduction average 17% accuracy, in contrast to our new HST parallaxes, which average 1% accuracy and have errors on the individual parallaxes ranging from 85 to 144 μas. These parallax data were combined with HST Advanced Camera for Surveys photometry in the F606W and F814W filters to obtain the absolute magnitudes of the stars with an accuracy of 0.02–0.03 mag. Six of these stars are on the main sequence (MS) (with ‑2.7 < [Fe/H] < ‑1.8) and are suitable for testing metal-poor stellar evolution models and determining the distances to metal-poor globular clusters (GCs). Using the abundances obtained by O’Malley et al., we find that standard stellar models using the VandenBerg & Clem color transformation do a reasonable job of matching five of the MS stars, with HD 54639 ([Fe/H] = ‑2.5) being anomalous in its location in the color–magnitude diagram. Stellar models and isochrones were generated using a Monte Carlo analysis to take into account uncertainties in the models. Isochrones that fit the parallax stars were used to determine the distances and ages of nine GCs (with ‑2.4 ≤ [Fe/H] ≤ ‑1.9). Averaging together the age of all nine clusters led to an absolute age of the oldest, most metal-poor GCs of 12.7 ± 1.0 Gyr, where the quoted uncertainty takes into account the known uncertainties in the stellar models and isochrones, along with the uncertainty in the distance and reddening of the clusters.

  16. Chronic Pain More Likely for Poor, Less Educated

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_163650.html Chronic Pain More Likely for Poor, Less Educated: Study Researchers ... 17, 2017 FRIDAY, Feb. 17, 2017 (HealthDay News) -- Chronic pain is much more common among poor, less educated ...

  17. Factors predicting poor prognosis in ischemic colitis

    PubMed Central

    Añón, Ramón; Boscá, Marta Maia; Sanchiz, Vicente; Tosca, Joan; Almela, Pedro; Amorós, Cirilo; Benages, Adolfo

    2006-01-01

    ). Stenosis was the only endoscopic finding that appeared more frequently in seriously ill patients than in slightly ill patients (66.6% vs 17.3%, P = 0.017). CONCLUSION: The factors that can predict poor prognosis of IC are the absence of hematochezia, tachycardia and peritonism, anemia and hyponatremia and stenosis. PMID:16937472

  18. Biomarkers of tobacco smoke exposure.

    PubMed

    Mattes, William; Yang, Xi; Orr, Michael S; Richter, Patricia; Mendrick, Donna L

    2014-01-01

    Diseases and death caused by exposure to tobacco smoke have become the single most serious preventable public health concern. Thus, biomarkers that can monitor tobacco exposure and health effects can play a critical role in tobacco product regulation and public health policy. Biomarkers of exposure to tobacco toxicants are well established and have been used in population studies to establish public policy regarding exposure to second-hand smoke, an example being the nicotine metabolite cotinine, which can be measured in urine. Biomarkers of biological response to tobacco smoking range from those indicative of inflammation to mRNA and microRNA patterns related to tobacco use and/or disease state. Biomarkers identifying individuals with an increased risk for a pathological response to tobacco have also been described. The challenge for any novel technology or biomarker is its translation to clinical and/or regulatory application, a process that requires first technical validation of the assay and then careful consideration of the context the biomarker assay may be used in the regulatory setting. Nonetheless, the current efforts to investigate new biomarker of tobacco smoke exposure promise to offer powerful new tools in addressing the health hazards of tobacco product use. This review will examine such biomarkers, albeit with a focus on those related to cigarette smoking.

  19. Ethanol exposure induces a delay in the reacquisition of function during head regeneration in Schmidtea mediterranea.

    PubMed

    Lowe, Jesse R; Mahool, Tyler D; Staehle, Mary M

    2015-01-01

    Prenatal exposure to ethanol affects neurodevelopmental processes, leading to a variety of physical and cognitive impairments collectively termed Fetal Alcohol Spectrum Disorders (FASD). The molecular level ethanol-induced alterations that underlie FASD are poorly understood and are difficult to study in mammals. Ethanol exposure has been shown to affect regulation and differentiation of embryonic stem cells in vitro, suggesting that in vivo effects such as FASD could arise from similar alterations of stem cells. In this study, we hypothesize that ethanol exposure affects head regeneration and neuroregeneration in the Schmidtea mediterranea planarian. S. mediterranea freshwater flatworms have remarkable regenerative abilities arising from an abundant population of pluripotent adult somatic stem cells known as neoblasts. Here, we evaluated the mobility-normalized photophobic behavior of ethanol-exposed planaria as an indicator of cognitive function in intact and head-regenerating worms. Our studies show that exposure to 1% ethanol induces a delay in the reacquisition of behavior during head regeneration that cannot be attributed to the effect of ethanol on intact worms. This suggests that the S. mediterranea planarian could provide insight into conserved neurodevelopmental processes that are affected by ethanol and that lead to FASD in humans.

  20. Advertising and the Poor. Journalism Monographs Number Seventy-Five.

    ERIC Educational Resources Information Center

    Bowen, Lawrence

    This monograph examines the impact of media advertising on the poor. The first half of the report discusses research on the conceptual styles of the poor, mass communication among the poor, and advertising and the low-income consumer. The second half describes the methodology and results of a study of the advertising evaluation capacity and…

  1. 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…

  2. 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…

  3. 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

  4. Developmental Alcohol Exposure Impairs Activity-Dependent S-Nitrosylation of NDEL1 for Neuronal Maturation.

    PubMed

    Saito, Atsushi; Taniguchi, Yu; Kim, Sun-Hong; Selvakumar, Balakrishnan; Perez, Gabriel; Ballinger, Michael D; Zhu, Xiaolei; Sabra, James; Jallow, Mariama; Yan, Priscilla; Ito, Koki; Rajendran, Shreenath; Hirotsune, Shinji; Wynshaw-Boris, Anthony; Snyder, Solomon H; Sawa, Akira; Kamiya, Atsushi

    2016-07-01

    Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.

  5. Inhalation exposure of animals.

    PubMed Central

    Phalen, R F

    1976-01-01

    Relative advantages and disadvantages and important design criteria for various exposure methods are presented. Five types of exposures are discussed: whole-body chambers, head-only exposures, nose or mouth-only methods, lung-only exposures, and partial-lung exposures. Design considerations covered include: air cleaning and conditioning; construction materials; losses of exposure materials; evenness of exposure; sampling biases; animal observation and care; noise and vibration control, safe exhausts, chamber loading, reliability, pressure fluctuations; neck seals, masks, animal restraint methods; and animal comfort. Ethical considerations in use of animals in inhalation experiments are also discussed. PMID:1017420

  6. 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

  7. 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

  8. 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

  9. 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.

  10. Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development.

    PubMed

    Gopalakrishnan, Kalpana; Teitelbaum, Susan L; Lambertini, Luca; Wetmur, James; Manservisi, Fabiana; Falcioni, Laura; Panzacchi, Simona; Belpoggi, Fiorella; Chen, Jia

    2017-01-01

    Exposure to environmental chemicals has been linked to altered mammary development and cancer risk at high doses using animal models. Effects at low doses comparable to human exposure remain poorly understood, especially during critical developmental windows. We investigated the effects of two environmental phenols commonly used in personal care products - methyl paraben (MPB) and triclosan (TCS) - on the histology and transcriptome of normal mammary glands at low doses mimicking human exposure during critical windows of development. Sprague-Dawley rats were exposed during perinatal, prepubertal and pubertal windows, as well as from birth to lactation. Low-dose exposure to MPB and TCS induced measurable changes in both mammary histology (by Masson's Trichrome Stain) and transcriptome (by microarrays) in a window-specific fashion. Puberty represented a window of heightened sensitivity to MPB, with increased glandular tissue and changes of expression in 295 genes with significant enrichment in functions such as DNA replication and cell cycle regulation. Long-term exposure to TCS from birth to lactation was associated with increased adipose and reduced glandular and secretory tissue, with expression alterations in 993 genes enriched in pathways such as cholesterol synthesis and adipogenesis. Finally, enrichment analyses revealed that genes modified by MPB and TCS were over-represented in human breast cancer gene signatures, suggesting possible links with breast carcinogenesis. These findings highlight the issues of critical windows of susceptibility that may confer heightened sensitivity to environmental insults and implicate the potential health effects of these ubiquitous environmental chemicals in breast cancer.

  11. Biological effects from electromagnetic field exposure and public exposure standards.

    PubMed

    Hardell, Lennart; Sage, Cindy

    2008-02-01

    During recent years there has been increasing public concern on potential health risks from power-frequency fields (extremely low frequency electromagnetic fields; ELF) and from radiofrequency/microwave radiation emissions (RF) from wireless communications. Non-thermal (low-intensity) biological effects have not been considered for regulation of microwave exposure, although numerous scientific reports indicate such effects. The BioInitiative Report is based on an international research and public policy initiative to give an overview of what is known of biological effects that occur at low-intensity electromagnetic fields (EMFs) exposure. Health endpoints reported to be associated with ELF and/or RF include childhood leukaemia, brain tumours, genotoxic effects, neurological effects and neurodegenerative diseases, immune system deregulation, allergic and inflammatory responses, breast cancer, miscarriage and some cardiovascular effects. The BioInitiative Report concluded that a reasonable suspicion of risk exists based on clear evidence of bioeffects at environmentally relevant levels, which, with prolonged exposures may reasonably be presumed to result in health impacts. Regarding ELF a new lower public safety limit for habitable space adjacent to all new or upgraded power lines and for all other new constructions should be applied. A new lower limit should also be used for existing habitable space for children and/or women who are pregnant. A precautionary limit should be adopted for outdoor, cumulative RF exposure and for cumulative indoor RF fields with considerably lower limits than existing guidelines, see the BioInitiative Report. The current guidelines for the US and European microwave exposure from mobile phones, for the brain are 1.6 W/Kg and 2 W/Kg, respectively. Since use of mobile phones is associated with an increased risk for brain tumour after 10 years, a new biologically based guideline is warranted. Other health impacts associated with exposure to

  12. 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

  13. [A study on thermal regulation disturbance in severely handicapped patients].

    PubMed

    Nishimura, M; Nishimura, S

    1991-05-01

    Forty-five severely handicapped patients were investigated on body temperature regulation. Poor regulation cases had CT scans showing severe third and lateral ventricle dilatation. Furthermore, in almost all poor regulation cases of perinatal and postnatal onset, CT scans showed extensive low density areas involving the frontal lobe. Electrophysiological studies (sSEP, ABR and blink reflex) could not show definite differences between poor regulation cases and good regulation cases. These findings suggest that hypothalamus, medial forebrain bundle and frontal lobe play important roles in body temperature regulation. On the other hand, perinatal or postnatal onset cases frequently had small body surface areas and low serum creatinine.

  14. 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.

  15. 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...

  16. 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.

  17. 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.

  18. Poor Performers: Supervisors’ and Subordinates’ Responses

    DTIC Science & Technology

    1981-06-01

    Technical Report 517 POOR PERFORMERS: SUPERVISORS’ AND SUBORDINATES’ RESPONSES t--4 )0~ Daniel R. Ilgen Purdue University Terrence R. Mitchell and...NUMBER Technical Report 517 !’,- 4. TITLE (and Subtitle) 5. TYPE OF REPORT & PERIOD COVERED POOR PERFORMERS: SUPERVISORS’ AND Technical Report...Continue on reverese aide if neceeeary and Identify by block number) Job performance Power Poor performers Performance feedback * Job interdependence

  19. Effects of poor hygiene on cytokine phenotypes in children in the tropics.

    PubMed

    Figueiredo, C A; Amorim, L D; Vaca, M; Chico, M E; Campos, A C; Barreto, M L; Cooper, P J

    2016-01-01

    We describe immune phenotypes (innate and adaptive cytokines) according to environmental exposure using latent class analysis. A total of 310 schoolchildren living in Ecuador were assayed for spontaneous cytokine production as well as mitogen (SEB)-stimulated cytokines in whole blood cultures. We collected data on environmental exposures by questionnaire and on intestinal parasites by examination of stool samples. Latent class analysis (LCA) was used to group children according to their innate (IL-6, IL-8, IL-10 and TNF-α) and adaptive (IL-5, IL-13, IL-17, IFN-γ and IL-10) cytokine profile. We also conducted multiple-group LCA and LCA with covariates to evaluate the effect of predictors on profile membership. We identified both hyporesponsive and Th2-modified immune phenotypes produced by peripheral blood leukocytes (PBLs) that were associated with intestinal worms and birth order, providing insights into how poor hygiene mediates immunologic effects on immune-mediated diseases.

  20. Dioxin Exposure Initiative

    EPA Pesticide Factsheets

    The Dioxin Exposure Initiative (DEI) is no longer active. This page contains a summary of the dioxin exposure initiative with illustrations, contact and background information.Originally supported by scientist Matthew Lorber, who retired in Mar 2017.

  1. National Exposure Research Laboratory

    EPA Pesticide Factsheets

    The Ecosystems Research Division of EPA’s National Exposure Research Laboratory, conducts research on organic and inorganic chemicals, greenhouse gas biogeochemical cycles, and land use perturbations that create stressor exposures and potentia risk

  2. 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 ...

  3. 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)

  4. 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...

  5. Occupational Noise Exposure

    MedlinePlus

    ... is pervasive. It is also preventable. More Exposure & Controls Exposure to loud noise kills the nerve endings ... endorse, takes no responsibility for, and exercises no control over the linked organization or its views, or ...

  6. 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...

  7. Breath testing and personal exposure--SIFT-MS detection of breath acetonitrile for exposure monitoring.

    PubMed

    Storer, Malina; Curry, Kirsty; Squire, Marie; Kingham, Simon; Epton, Michael

    2015-05-26

    Breath testing has potential for the rapid assessment of the source and impact of exposure to air pollutants. During the development of a breath test for acetonitrile using selected ion flow tube mass spectrometry (SIFT-MS) raised acetonitrile concentrations in the breath of volunteers were observed that could not be explained by known sources of exposure. Workplace/laboratory exposure to acetonitrile was proposed since this was common to the volunteers with increased breath concentrations. SIFT-MS measurements of acetonitrile in breath and air were used to confirm that an academic chemistry laboratory was the source of exposure to acetonitrile, and quantify the changes that occurred to exhaled acetonitrile after exposure. High concentrations of acetonitrile were detected in the air of the chemistry laboratory. However, concentrations in the offices were not significantly different across the campus. There was a significant difference in the exhaled acetonitrile concentrations of people who worked in the chemistry laboratories (exposed) and those who did not (non-exposed). SIFT-MS testing of air and breath made it possible to determine that occupational exposure to acetonitrile in the chemistry laboratory was the cause of increased exhaled acetonitrile. Additionally, the sensitivity was adequate to measure the changes to exhaled amounts and found that breath concentrations increased quickly with short exposure and remained increased even after periods of non-exposure. There is potential to add acetonitrile to a suite of VOCs to investigate source and impact of poor air quality.

  8. Second-degree bachelor of science in nursing students' preconceived attitudes toward the homeless and poor: a pilot study.

    PubMed

    Boylston, Mary T; O'Rourke, Rosemarie

    2013-01-01

    The current economic climate of the United States has contributed to the crisis in health care delivery services. As a result, an increasing number of individuals present as poor and vulnerable. Currently, poverty rates in the United States are climbing, with literature clearly reflecting an association between poverty and ill health. With a number of economic barriers to health care, it has been suggested that health care providers' attitudes and subtle prejudices have also contributed to access. These preconceived negative attitudes can shame and embarrass vulnerable, homeless, immigrant, and poor individuals from attempting to access care. This research attempted to identify preconceived attitudes that second-degree baccalaureate nursing students possess prior to clinical exposure to poor and homeless populations through qualitative and quantitative investigative methods. Senior-level community health students preparing to deliver health care at a suburban homeless day shelter were asked to describe their experiences and opinions relative to homeless and poor persons before and after their actual contact with this population. Collected data suggest that there are subtle stereotyping and negative attitudes regarding the plight of overtly impoverished individuals before rendering care. After an 8-hour clinical experience with the aforementioned population, attitudes toward the vulnerable slightly improved, suggesting that clinical and didactic exposure to the plight of poor populations may assist to sensitize student nurses to exude compassion through a holistic therapeutic nurse-client relationship.

  9. 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…

  10. 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.

  11. Gestational and lactational exposure to low-dose bisphenol A increases Th17 cells in mice offspring.

    PubMed

    Luo, Shimeng; Li, Yun; Li, Yingpei; Zhu, Qixing; Jiang, Jianhua; Wu, Changhao; Shen, Tong

    2016-10-01

    Increasing evidence demonstrates that perinatal exposure to Bisphenol A (BPA) can cause immune disorders throughout the life span. However, the biological basis for these immune disorders is poorly understood and the effects of exposure to BPA on Th17 development are unknown. The present study sought to characterize alterations of Th17 cells in childhood and adulthood following gestational and lactational exposure to environmentally relevant low-dose of BPA and the underlying mechanisms. Pregnant dams were exposed to BPA (10, 100 or 1000nM) via drinking water from gestational day (GD) 0 to postnatal day (PND) 21. At PNDs 21 and 42, offspring mice were anesthetized, blood was obtained for cytokine assay and spleens were collected for Th17 cell frequency and RORγt mRNA expression analysis. Perinatal exposure to low-dose BPA resulted in a dose-dependent and gender-specific persistent rise in Th17 cells accompanied by an increase of RORγt mRNA expression in the offsprings. The contents of major Th17 cell-derived cytokines (IL-17 and IL-21) and those essential for Th17 cell differentiation (IL-6 and IL-23) were also increased compared to those in controls. These changes were more pronounced in female than in male offsprings. However, perinatal exposure to low-dose BPA had little effect on serum TGF-β, another key regulator for Th17 cell development. Our results suggest that gestational and lactational exposure to a low-dose of BPA can affect Th17 cell development via an action on its transcription factor and the regulatory cytokines. These findings provide novel insight into sustained immune disorders by BPA exposure during development.

  12. Environmental exposure to lead (Pb) and variations in its susceptibility.

    PubMed

    Kim, Jina; Lee, Youngeun; Yang, Mihi

    2014-01-01

    Based on exposure frequency and intrinsic toxicity, lead (Pb) ranks one of the highest priority toxic materials. Continuous regulation of environmental Pb exposure has contributed to dramatically diminished exposure levels of Pb, for example, blood level of Pb. However, the safety level of Pb is not established, as low-level exposure to Pb still shows severe toxicity in high susceptible population and late onset of some diseases from early exposure. In the present study, we focused on food-borne Pb exposure and found broad variations in Pb exposure levels via food among countries. In addition, there are genetic or ethnical variations in Pb-targeted and protective genes. Moreover, various epigenetic alterations were induced by Pb poisoning. Therefore, we suggest a systemic approach including governmental (public) and individual prevention from Pb exposure with continuous biological monitoring and genetic or epigenetic consideration.

  13. Drywall construction and asbestos exposure.

    PubMed

    Fischbein, A; Rohl, A N; Langer, A M; Selikoff, I J

    1979-05-01

    The rapid development of the drywall construction trade in the United States is described. It is estimated that some 75,000 U.S. construction workers are currently employed in this trade. The use of a variety of spackle and taping compounds is shown to be associated with significant asbestos exposure; air samples taken in the breathing zone by drywall tapers during sanding of taping compounds show fiber concentrations exceeding, by several times, the maximum level permitted by United States Government regulations. These findings are given together with the result of a clinical field survey of drywall construction workers demonstrating that asbestos disease may be an important health hazard in this trade.

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. Metropolitan Influences on Migration into Poor and Nonpoor Neighborhoods*

    PubMed Central

    South, Scott J.; Pais, Jeremy; Crowder, Kyle

    2011-01-01

    Data from the Panel Study of Income Dynamics and three decennial U.S. censuses are used to examine the influence of metropolitan-area characteristics on black and white households' propensity to move into poor versus nonpoor neighborhoods. We find that a nontrivial portion of the variance in the odds of moving to a poor rather to a nonpoor neighborhood exists between metropolitan areas. Net of established individual-level predictors of inter-neighborhood migration, black and white households are more likely to move to a poor or extremely poor tract rather than to a nonpoor tract in metropolitan areas containing many poor neighborhoods and a paucity of recently-built housing in nonpoor areas. Blacks are especially likely to move to a poor tract in metropolitan areas characterized by high levels of racial residential segregation and in which poor tracts have a sizeable concentration of blacks. White households are more likely to move to a poor than to a nonpoor tract in metropolitan areas that have comparatively few African Americans. PMID:21625368

  19. Addressing Classism, Extending Multicultural Competence, and Serving the Poor: Reply

    ERIC Educational Resources Information Center

    Smith, Laura

    2006-01-01

    Replies to comments on "Psychotherapy, classism, and the poor: Conspicuous by their absence" (see record 2005-11834-002). In this article, the current author outlined what psychologists over the past four decades have had to say about the field's neglect of the poor in its research, practice, and theory. Characterizing this exclusion of the poor…

  20. 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…

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. The Prevalence of Poor Reading in Dutch Special Elementary Education

    ERIC Educational Resources Information Center

    van Bon, Wim H. J.; Bouwmans, Mieke; Broeders, Ivy N. L. D. C.

    2006-01-01

    The relative frequency of poor readers in Dutch general elementary education (GEE) and special elementary education (SEE) and the characteristics of their reading performance were investigated using a lexical decision procedure. According to the same norms that identified 9% of students as poor readers in GEE, no less than 73% of the students in…

  6. Exposure Factors Handbook Chapter 16

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  7. Exposure Factors Handbook Chapter 18

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  8. Exposure Factors Handbook Chapter 14

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  9. Exposure Factors Handbook Chapter 15

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  10. Exposure Factors Handbook Chapter 6

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  11. Exposure Factors Handbook Chapter 10

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  12. Exposure Factors Handbook Chapter 9

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  13. Exposure Factors Handbook Chapter 13

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  14. Exposure Factors Handbook (2011 Edition)

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  15. Exposure Factors Handbook Chapter 8

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  16. Exposure Factors Handbook Chapter 5

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  17. Exposure Factors Handbook Chapter 3

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  18. Exposure Factors Handbook Chapter 17

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  19. Exposure Factors Handbook Chapter 2

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  20. Exposure Factors Handbook Chapter 12

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  1. Exposure Factors Handbook Chapter 11

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  2. Exposure Factors Handbook Chapter 7

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  3. Exposure Factors Handbook Chapter 19

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  4. Exposure Factors Handbook Chapter 1

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  5. Exposure Factors Handbook Chapter 4

    EPA Pesticide Factsheets

    Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

  6. Transgenerational latent early-life associated regulation unites environment and genetics across generations.

    PubMed

    Lahiri, Debomoy K; Maloney, Bryan; Bayon, Baindu L; Chopra, Nipun; White, Fletcher A; Greig, Nigel H; Nurnberger, John I

    2016-03-01

    The origin of idiopathic diseases is still poorly understood. The latent early-life associated regulation (LEARn) model unites environmental exposures and gene expression while providing a mechanistic underpinning for later-occurring disorders. We propose that this process can occur across generations via transgenerational LEARn (tLEARn). In tLEARn, each person is a 'unit' accumulating preclinical or subclinical 'hits' as in the original LEARn model. These changes can then be epigenomically passed along to offspring. Transgenerational accumulation of 'hits' determines a sporadic disease state. Few significant transgenerational hits would accompany conception or gestation of most people, but these may suffice to 'prime' someone to respond to later-life hits. Hits need not produce symptoms or microphenotypes to have a transgenerational effect. Testing tLEARn requires longitudinal approaches. A recently proposed longitudinal epigenome/envirome-wide association study would unite genetic sequence, epigenomic markers, environmental exposures, patient personal history taken at multiple time points and family history.

  7. [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.

  8. Low vagal tone magnifies the association between psychosocial stress exposure and internalizing psychopathology in adolescents.

    PubMed

    McLaughlin, Katie A; Rith-Najarian, Leslie; Dirks, Melanie A; Sheridan, Margaret A

    2015-01-01

    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.

  9. Virtual reality exposure therapy.

    PubMed

    Rothbaum, B O; Hodges, L; Kooper, R

    1997-01-01

    It has been proposed that virtual reality (VR) exposure may be an alternative to standard in vivo exposure. Virtual reality integrates real-time computer graphics, body tracking devices, visual displays, and other sensory input devices to immerse a participant in a computer-generated virtual environment. Virtual reality exposure is potentially an efficient and cost-effective treatment of anxiety disorders. VR exposure therapy reduced the fear of heights in the first controlled study of virtual reality in treatment of a psychiatric disorder. A case study supported the efficacy of VR exposure therapy for the fear of flying. The potential for virtual reality exposure treatment for these and other disorders is explored, and therapeutic issues surrounding the delivery of VR exposure are discussed.

  10. 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

  11. 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.

  12. Sound Exposure During Outdoor Music Festivals

    PubMed Central

    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

  13. 64 FR 32447 - Occupational Exposure to Tuberculosis

    Federal Register 2010, 2011, 2012, 2013, 2014

    1999-06-17

    ... Tuberculosis AGENCY: Occupational Safety and Health Administration (OSHA), Department of Labor. ACTION: Notice... standard to regulate occupational exposure to tuberculosis (TB). Public hearings on the proposal were held... Tuberculosis'' (Ex. 179-3); ``Laboratory Performance Evaluation of N95 Filtering Facepiece Respirators,...

  14. 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...

  15. Exposure scenarios for workers.

    PubMed

    Marquart, Hans; Northage, Christine; Money, Chris

    2007-12-01

    The new European chemicals legislation REACH (Registration, Evaluation, Authorisation and restriction of Chemicals) requires the development of Exposure Scenarios describing the conditions and risk management measures needed for the safe use of chemicals. Such Exposure Scenarios should integrate considerations of both human health and the environment. Specific aspects are relevant for worker exposure. Gathering information on the uses of the chemical is an important step in developing an Exposure Scenario. In-house information at manufacturers is an important source. Downstream users can contribute information through direct contact or through their associations. Relatively simple approaches (Tier 1 tools, such as the ECETOC Targeted Risk Assessment and the model EASE) can be used to develop broad Exposure Scenarios that cover many use situations. These approaches rely on the categorisation of just a few determinants, including only a small number of risk management measures. Such approaches have a limited discriminatory power and are rather conservative. When the hazard of the substance or the complexity of the exposure situation require a more in-depth approach, further development of the Exposure Scenarios with Tier 2 approaches is needed. Measured data sets of worker exposure are very valuable in a Tier 2 approach. Some downstream user associations have attempted to build Exposure Scenarios based on measured data sets. Generic Tier 2 tools for developing Exposure Scenarios do not exist yet. To enable efficient development of the worker exposure part of Exposure Scenarios a further development of Tier 1 and Tier 2 tools is needed. Special attention should be given to user friendliness and to the validity (boundaries) of the approaches. The development of standard worker exposure descriptions or full Exposure Scenarios by downstream user branches in cooperation with manufacturers and importers is recommended.

  16. [Occupational exposure to nanoparticles. Assessment of workplace exposure].

    PubMed

    Bujak-Pietrek, Stella

    2010-01-01

    Nanotechnology is currently one of the most popular branch of science. It is a technology that enables designing, manufacturing and application of materials and structures of very small dimensions, and its products are applied in almost every field of life. Nanoparticles are the structures having one or more dimensions of the order of 100 nm or less. They are used in precise mechanics, electronics, optics, medicine, pharmacy, cosmetics and many other spheres. Due to their very small size, nanostructures have completely different and specific properties, unknown for the bulk of materials. Fast-growing nanotechnology provides a wide spectrum of applications, but it also brings about new and unknown danger to human health. Nanotechnology is the branch that has developed rather recently, and much information about health risk and its influence on the environment is beyond our knowledge. Nanoparticles, released in many technological processes, as well as manufactured nanoparticles can induce occupational hazards to workers. The lack of regulations and standards, compulsory in the manufacture and use ofnanoparticles is a fundamental problem faced in the evaluation of exposure. Another problem is the choice of proper measurement equipment for surveying of very small particles - their number, mass and surface area in the workpost air. In this article, the possibility and scope of exposure assessment is discussed and a brief specification of available instrumentation for counting and assessing the parameters essential for classifying the exposure to nanoparticles is presented.

  17. 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…

  18. [Adaptive changes in the body upon exposure to electromagnetic radiation].

    PubMed

    Zubkova, S M

    1996-01-01

    The chance to use electromagnetic exposures as active adaptogen and the detecting of adaptive changes following them were objects of our studies. The data of experimental and clinical studies significative the dependence of changes on the functional state of organism were seen. Particular attention is paid to the site of exposure and to the advantages in the action of electromagnetic exposures on areas overlaying the endocrine glands and control centers of central nerve system. In these conditions electromagnetic exposures play a part of trigger initiated natural processes of homeostatic regulation in the organism functional systems. It is shown that the course of electromagnetic exposures in wide frequency range until laser radiation (infrared and red) arises adaptive changes of the regulator systems, of the bioenergetic and the biosynthetic processes in myocardium, liver, brain, thymus and other tissues predetermined genetically and secured the power of the adaptive systems. The cross-adaptation effects underlie the electromagnetic exposures medical action.

  19. 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.

  20. Exposure to double-stranded RNA mediated by tobacco rattle virus leads to transcription up-regulation of effector gene Mi-vap-2 from Meloidogyne incognita and promotion of pathogenicity in progeny.

    PubMed

    Chi, Yuankai; Wang, Xuan; Le, Xiuhu; Ju, Yuliang; Guan, Tinglong; Li, Hongmei

    2016-02-01

    Meloidogyne spp. are economically important plant parasites and cause enormous damage to agriculture world-wide. These nematodes use secreted effectors which modify host cells, allowing them to obtain the nutrients required for growth and development. A better understanding of the roles of effectors in nematode parasitism is critical for understanding the mechanisms of nematode-host interactions. In this study, Mi-vap-2 of Meloidogyne incognita, a gene encoding a venom allergen-like protein, was targeted by RNA interference mediated by the tobacco rattle virus. Unexpectedly, compared with a wild type line, a substantial up-regulation of Mi-vap-2 transcript was observed in juveniles collected at 7 days p.i. from Nicotiana benthamiana agroinfiltrated with TRV::vap-2. This up-regulation of the targeted transcript did not impact development of females or the production of galls, nor the number of females on the TRV::vap-2 line. In a positive control line, the transcript of Mi16D10 was knocked down in juveniles from the TRV::16D10 line at 7 days p.i., resulting in a significant inhibition of nematode development. The up-regulation of Mi-vap-2 triggered by TRV-RNAi was inherited by the progeny of the nematodes exposed to double-stranded RNA. Meanwhile, a substantial increase in Mi-VAP-2 expression in those juvenile progeny was revealed by ELISA. This caused an increase in the number of galls (71.2%) and females (84.6%) produced on seedlings of N. benthamiana compared with the numbers produced by control nematodes. Up-regulation of Mi-vap-2 and its encoded protein therefore enhanced pathogenicity of the nematodes, suggesting that Mi-vap-2 may be required for successful parasitism during the early parasitic stage of M. incognita.