Science.gov

Sample records for poorly regulated exposure

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

    PubMed

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

    1992-12-01

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

  2. Household instability and self-regulation among poor children

    PubMed Central

    McCoy, Dana Charles; Raver, C. Cybele

    2015-01-01

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

  3. Calcineurin: a poorly understood regulator of muscle mass.

    PubMed

    Hudson, Matthew B; Price, S Russ

    2013-10-01

    This review will discuss the existing literature that has examined the role of calcineurin (CnA) in the regulation of skeletal muscle mass in conditions associated with hypertrophic growth or atrophy. Muscle mass is determined by the balance between protein synthesis and degradation which is controlled by a number of intracellular signaling pathways, most notably the insulin/IGF/phosphatidylinositol 3-kinase (PI3K)/Akt system. Despite being activated by IGF-1 and having well-described functions in the determination of muscle fiber phenotypes, calcineurin (CnA), a Ca(2+)-activated serine/threonine phosphatase, and its downstream signaling partners have garnered little attention as a regulator of muscle mass. Compared to other signaling pathways, the relatively few studies that have examined the role of CnA in the regulation of muscle size have produced discordant results. The reasons for these differences is not obvious but may be due to the selective nature of the genetic models studied, fluctuations in the endogenous level of CnA activity in various muscles, and the variable use of CnA inhibitors to inhibit CnA signaling. Despite the inconsistent nature of the outcomes, there is sufficient direct and indirect evidence to conclude that CnA plays a role in the regulation of skeletal muscle mass. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. PMID:23838168

  4. Genome exposure and regulation in mammalian cells.

    PubMed

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

    1998-09-01

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

  5. 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.

  6. Rat lung tumors induced by exposure to selected poorly soluble nonfibrous particles.

    PubMed

    Nikula, K J

    2000-01-01

    Rodent bioassays have been used to assess the carcinogenicity of several inhaled, poorly soluble, nonfibrous particles that vary in toxicity and carcinogenic potency. There is substantial published information from chronic inhalation bioassays of diesel exhaust, carbon black, titanium dioxide, talc, and coal dust. This review summarizes data from studies with exposures for 2 yr or more using these 5 materials. The review has four objectives: (1) to summarize the current information available from these bioassays concerning exposure-dose-carcinogenic response in rats, (2) to summarize the pathologic and phenotypic features of the neoplastic response in rats, (3) to examine possible strain- and gender-related differences, and (4) to compare the neoplastic responses of rat to those of other species exposed to these materials.

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

    PubMed Central

    Lepore, Stephen J.; Kliewer, Wendy

    2013-01-01

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

  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. 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

  10. 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. PMID:25214512

  11. Neurohumoral blood pressure regulation in lead exposure

    SciTech Connect

    Boscolo, P.; Carmignani, M.

    1988-06-01

    Previous human studies demonstrated that lead exposure may modify the metabolism of catecholamines and of hormones controlled by the hypothalamo-pituitary axis and may affect the kallikrein-kinin system. This paper reports unpublished data on the plasma renin activity of lead-exposed workers; these results are in agreement with those of previous human and experimental studies suggesting that the synthesis or release of renin is increased after short and moderate exposure to inorganic lead and reduced whenever the exposure is prolonged. Previous experimental investigations demonstrated that lead may act on the cardiovascular system, with effects on the renin-angiotensin system, on the reactivity to stimulation of peripheral catecholaminergic receptors, on sympathetic and vagal tone, and on reactivity to the stimulation of baroreceptors. This paper reports the results of a study on male Sprague-Dawley rats that received 0, 15, 30, and 60 ..mu..g/mL of lead in drinking water for 18 months. Blood pressure was increased in the rats receiving 30 and 60 ppm of lead; cardiac inotropism was augmented only in those receiving the higher dose of the metal, and heart rate was not modified. Cardiovascular responses to agonists indicated that lead exposure affects the renin-angiotensin system and induces sympathetic hyperactivity be acting on central and peripheral sympathetic junctions increasing the responsiveness to stimulation of ..cap alpha../sub 2/-adrenoreceptors and by increasing the reactivity to stimulation of cardiac and vascular ..beta..-adrenergic and dopaminergic receptors.

  12. Chloride channel-3 promotes tumor metastasis by regulating membrane ruffling and is associated with poor survival

    PubMed Central

    Li, Qin; Deng, Lulu; Wu, Hui; Lin, Guixian; Chen, Lixin; Zhang, Haifeng; Li, Chunmei; Wang, Liwei; Zhu, Jiayong; Wang, Weizhang; Chu, Fujiang; Shen, Juan; Li, Hongzhi; Mao, Jianwen

    2015-01-01

    The chloride channel-3 (ClC-3) protein is known to be a component of Cl− channels involved in cell volume regulation or acidification of intracellular vesicles. Here, we report that ClC-3 was highly expressed in the cytoplasm of metastatic carcinomatous cells and accelerated cell migration in vitro and tumor metastasis in vivo. High-grade expression of cytoplasmic ClC-3 predicted poor survival in cancer patients. We found that independent of its volume-activated Cl− channel properties, ClC-3 was able to promote cell membrane ruffling, required for tumor metastasis. ClC-3 mediated membrane ruffling by regulating keratin 18 phosphorylation to control β1 Integrin recycling. Therefore, cytoplasmic ClC-3 plays an active and key role in tumor metastasis and may be a valuable prognostic biomarker and a therapeutic target to prevent tumor spread. PMID:25537517

  13. Effects of prenatal cocaine exposure on infant reactivity and regulation

    PubMed Central

    Eiden, Rina D.; McAuliffe, Shannon; Kachadourian, Lorig; Coles, Claire; Colder, Craig; Schuetze, Pamela

    2009-01-01

    The purpose of this study was to examine the role of prenatal cocaine exposure and associated risk factors on infant reactivity and regulation at 7 months of infant age. Participants consisted of 167 mother-infant dyads participating in an ongoing longitudinal study of prenatal cocaine exposure, who completed the arm-restraint procedure at the 7-month assessment (87 cocaine exposed, 80 non-cocaine exposed). We hypothesized that cocaine exposed infants would display higher arousal or reactivity and lower regulation during a procedure designed to arouse anger/frustration. Results indicated that cocaine exposed infants were more reactive to increases in the level of stress from trial 1 to trial 2 but exhibited no change in the number of regulatory strategies as stress increased, unlike the control group infants. Infant birth weight moderated the association between cocaine exposure and infant regulation. Among cocaine exposed infants, those with lower birth weight displayed higher reactivity compared to those with higher birth weight. Contrary to expectations, there were no indirect effects between cocaine exposure and infant reactivity/regulation via environmental risk, parenting, or birth weight. Results are supportive of a teratological model of prenatal cocaine exposure for infant reactivity/regulation in infancy. PMID:18822371

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  15. Poor psychometric scores of children living in isolated riverine and agrarian communities and fish-methylmercury exposure.

    PubMed

    Fonseca, Márlon de F; Dórea, José G; Bastos, Wanderley R; Marques, Rejane C; Torres, João P M; Malm, Olaf

    2008-11-01

    Because of heavy dependence on fish, Amazonian riparian communities are chronically exposed to high levels of methylmercury (MeHg). We studied fish-MeHg exposure (total hair-Hg, HHg) as a determinant of neurocognitive scores of children living in two geographically distant, culturally distinct and isolated poor communities of non-urban environments: Amazonian riverines (Riparians, n=38) of the Puruzinho Lake community in the Rio Madeira Basin and rural agrarians from Iúna, Espírito Santo (Agrarians, n=32). Nutritional status was estimated by anthropometry (Z-scores) and individual cognitive abilities were assessed by the Wechsler Intelligence Scale for Children-III (WISC-III) and the Human Figure Drawings (HFD), both validated versions for Brazilian children. Anthropometric assessment showed slightly elevated Z-scores for the Agrarian children (not statistically significant) but median HHg concentrations were 14.4 and 0.25microgg(-1) respectively for Riparian and Agrarian children (p=0.000). Despite paradoxical MeHg exposures, both groups showed comparable HFD scores but very poor performance in WISC-III test battery; median of sum of WISC-III subtests scores (SigmaTOT) were 17.9 and 28.6 (p<0.000) for Riparian and Agrarian children, respectively (percentage scale). Spearman correlation between nutritional status (attained growth) and psychometric scores were statistically significant between height-for-age Z-score and Object Assembly subtest (r=0.269; p=0.043), SigmaTOT (r=0.319; p=0.016), Performance-IQ (r=0.311; p=0.019) and Perceptual Organization Index scores (r=0.302; p=0.023). In these isolated communities there are stronger determinants of neurocognitive poor performance than MeHg exposure. Global strategies for reducing human exposure to MeHg by curtailing fish consumption are unrealistic options for riverine subsistence populations and are not justifiable to prevent low cognitive scores.

  16. 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…

  17. CUEDC2 down-regulation is associated with tumor growth and poor prognosis in lung adenocarcinoma

    PubMed Central

    Wang, Ran; Liu, Yangli; Cai, Jinghuang; Guo, Yubiao; Zhu, Zhiwen; Xie, Canmao

    2015-01-01

    CUE domain-containing 2 (CUEDC2) is a multi-functional protein, which regulates cell cycle, growth factor signaling and inflammation. We found that CUEDC2 was low in lung adenocarcinoma cell lines and lung adenocarcinoma tissues at both mRNA and protein levels. Low levels of CUEDC2 were correlated with a shorter survival time in patients with lung adenocarcinoma (p = 0.004). CUEDC2 expression was correlated with tumor T classification (P = 0.001) at clinical stage (P = 0.001) and tumor size (P = 0.033). Multivariate analysis suggested that CUEDC2 expression is an independent prognostic indicator for patients with lung adenocarcinoma. Ectopic expression of CUEDC2 decreased cell proliferation in vitro and inhibited tumor growth in nude mice in vivo. Knockdown of endogenous CUEDC2 by short hairpin RNAs (shRNAs) increased tumor growth. Inhibition of proliferation by CUEDC2 was associated with inactivation of the PI3K/Akt pathway, induction of p21 and down-regulation of cyclin D1. Our results suggest that decreased expression of CUEDC2 contributes to tumor growth in lung adenocarcinoma, leading to a poor clinical outcome. PMID:26023733

  18. CUEDC2 down-regulation is associated with tumor growth and poor prognosis in lung adenocarcinoma.

    PubMed

    Sun, Longhua; Bai, Lihong; Lin, Gengpeng; Wang, Ran; Liu, Yangli; Cai, Jinghuang; Guo, Yubiao; Zhu, Zhiwen; Xie, Canmao

    2015-08-21

    CUE domain-containing 2 (CUEDC2) is a multi-functional protein, which regulates cell cycle, growth factor signaling and inflammation. We found that CUEDC2 was low in lung adenocarcinoma cell lines and lung adenocarcinoma tissues at both mRNA and protein levels. Low levels of CUEDC2 were correlated with a shorter survival time in patients with lung adenocarcinoma (p = 0.004). CUEDC2 expression was correlated with tumor T classification (P = 0.001) at clinical stage (P = 0.001) and tumor size (P = 0.033). Multivariate analysis suggested that CUEDC2 expression is an independent prognostic indicator for patients with lung adenocarcinoma. Ectopic expression of CUEDC2 decreased cell proliferation in vitro and inhibited tumor growth in nude mice in vivo. Knockdown of endogenous CUEDC2 by short hairpin RNAs (shRNAs) increased tumor growth. Inhibition of proliferation by CUEDC2 was associated with inactivation of the PI3K/Akt pathway, induction of p21 and down-regulation of cyclin D1. Our results suggest that decreased expression of CUEDC2 contributes to tumor growth in lung adenocarcinoma, leading to a poor clinical outcome.

  19. Cumulative Anticholinergic Exposure Is Associated with Poor Memory and Executive Function in Older Men

    PubMed Central

    Han, Ling; Agostini, Joseph V.; Allore, Heather G.

    2014-01-01

    OBJECTIVES To examine the longitudinal relationship between cumulative exposure to anticholinergic medications and memory and executive function in older men. DESIGN Prospective cohort study. SETTING A Department of Veterans Affairs primary care clinic. PARTICIPANTS Five hundred forty-four community-dwelling men aged 65 and older with diagnosed hypertension. MEASUREMENTS The outcomes were measured using the Hopkins Verbal Recall Test (HVRT) for short-term memory and the instrumental activity of daily living (IADL) scale for executive function at baseline and during follow-up. Anticholinergic medication use was ascertained using participants' primary care visit records and quantified as total anticholinergic burden using a clinician-rated anti-cholinergic score. RESULTS Cumulative exposure to anticholinergic medications over the preceding 12 months was associated with poorer performance on the HVRT and IADLs. On average, a 1-unit increase in the total anticholinergic burden per 3 months was associated with a 0.32-point (95% confidence interval (CI) = 0.05–0.58) and 0.10-point (95% CI = 0.04–0.17) decrease in the HVRT and IADLs, respectively, independent of other potential risk factors for cognitive impairment, including age, education, cognitive and physical function, comorbidities, and severity of hypertension. The association was attenuated but remained statistically significant with memory (0.29, 95% CI = 0.01–0.56) and executive function (0.08, 95% CI = 0.02–0.15) after further adjustment for concomitant non-anticholinergic medications. CONCLUSION Cumulative anticholinergic exposure across multiple medications over 1 year may negatively affect verbal memory and executive function in older men. Prescription of drugs with anticholinergic effects in older persons deserves continued attention to avoid deleterious adverse effects. PMID:19093918

  20. 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

  1. Prevalence of subjective poor health symptoms associated with exposure to electromagnetic fields among university students.

    PubMed

    Mortazavi, S M J; Ahmadi, J; Shariati, M

    2007-05-01

    The number of people complaining about different symptoms that may be associated with exposure to electromagnetic fields (EMF) has increased rapidly during past years. Students use both mobile phones and video display terminals frequently. The purpose of this study was to investigate the association of mobile phone use and EMF health hazards. Basic demographic data and self-reported symptoms were sought using a questionnaire administered to all apparently healthy students at Rafsanjan University of Medical Sciences (RUMS) and Vali-e-Asr University (VAU). Questions about some major confounding factors such as age, gender, amount of video display terminal work were also included. Exact Fischer Test was used for data analysis. Among self-reported symptoms, headache (53.5%), fatigue (35.6%), difficulties in concentration (32.5%), vertigo/dizziness (30.4%), attention disorders (28.8%), nervousness (28.1%), palpitation (14.7%), low back pain (14.3%), myalgia (12.4%), and tinnitus (9.9%) were the main self-reported symptoms. No significant differences in the prevalence of these symptoms were found between CRT users and those who did not use CRTs. A significant association was found between cordless phone use and difficulties in concentration (P < .05) or attention disorders (P < .05). However, after correction of the gender role, these differences were not significant. No association was found between mobile phone use and the above-mentioned symptoms. No significantly higher prevalence of self-reported symptoms was found in individuals who had used mobile phones, video display terminals or cordless phones more frequently than others. Mass-media's lack of interest in the possible hazards of exposure to EMF in developing countries can explain the difference observed between the results of this study and those of other researchers in some developed countries who have shown an association between EMF exposure and the prevalence of self-reported subjective symptoms. This

  2. Regulation of TB vaccine-induced airway luminal T cells by respiratory exposure to endotoxin.

    PubMed

    Chen, Xuerong; Xiu, Fangming; Horvath, Carly N; Damjanovic, Daniela; Thanthrige-Don, Niroshan; Jeyanathan, Mangalakumari; Xing, Zhou

    2012-01-01

    Tuberculosis (TB) vaccine-induced airway luminal T cells (ALT) have recently been shown to be critical to host defense against pulmonary TB. However, the mechanisms that maintain memory ALT remain poorly understood. In particular, whether respiratory mucosal exposure to environmental agents such as endotoxin may regulate the size of vaccine-induced ALT population is still unclear. Using a murine model of respiratory genetic TB vaccination and respiratory LPS exposure, we have addressed this issue in the current study. We have found that single or repeated LPS exposure increases the number of antigen-specific ALT which are capable of robust secondary responses to pulmonary mycobacterial challenge. To investigate the potential mechanisms by which LPS exposure modulates the ALT population, we have examined the role of ALT proliferation and peripheral T cell recruitment. We have found that LPS exposure-increased ALT is not dependent on increased ALT proliferation as respiratory LPS exposure does not significantly increase the rate of proliferation of ALT. But rather, we find it to be dependent upon the recruitment of peripheral T cells into the airway lumen as blockade of peripheral T cell supplies markedly reduces the initially increased ALT. Thus, our data suggest that environmental exposure to airborne agents such as endotoxin has a profound modulatory effect on TB vaccine-elicited T cells within the respiratory tract. Our study provides a new, M.tb antigen-independent mechanism by which the respiratory mucosal anti-TB memory T cells may be maintained.

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

    PubMed

    Kolosov, Dennis; Kelly, Scott P

    2016-08-01

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

  4. 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

  5. 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.

  6. 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.

  7. 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

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

    PubMed

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

    2015-12-07

    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.

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

    PubMed Central

    2014-01-01

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

  10. 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

  11. Chronic exposure to hexachlorobenzene results in down-regulation of connexin43 in the breast.

    PubMed

    Delisle, Ariane; Ferraris, Emanuelle; Plante, Isabelle

    2015-11-01

    Decreased expression of connexins has been associated with cancer, but the underlying mechanisms are poorly understood. We have previously shown that a 5 day exposure to hexachlorobenzene (HCB) resulted in decreased connexins expression in hepatocytes 45 days later, and that this down-regulation was linked to activation of Akt through the ILK pathway. Because HCB promotes cancer in both the liver and breast, the present study aimed to determine if the mechanisms are similar in both tissues. MCF-12A breast cells were thus transfected with vectors coding for either Akt or a constitutively active form of Akt. In those cells, activation of Akt was correlated with decreased Cx43 levels. Female rats were then exposed to HCB by gavage either following the same protocol used previously for the liver or through a chronic exposure. While no changes were observed after the 5 days exposure protocol, chronic exposure to HCB resulted in increased Akt levels and decreased Cx43 levels in breast cells. In vitro, Akt was activated in MCF-12A cells exposed to HCB either for 7 days or chronically, but no changes were observed in junctional proteins. Together, these results suggested that, while activation of Akt can decrease Cx43 expression in breast cells in vitro, other mechanisms are involved during HCB exposure, leading to a decrease in Cx43 levels in a model- and duration-dependent manner. Finally, we showed that HCB effects are tissue specific, as we did not observe the same results in breast and liver tissues.

  12. 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.

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

    PubMed Central

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

    2011-01-01

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

  14. 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.

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2016-02-29

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

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

    PubMed

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

    2016-02-29

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

  18. 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

  19. 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…

  20. 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.

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

    PubMed

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

    2015-06-01

    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.

  2. Myofibrillogenesis regulator-1 overexpression is associated with poor prognosis of gastric cancer patients

    PubMed Central

    Guo, Jing; Dong, Bin; Ji, Jia-Fu; Wu, Ai-Wen

    2012-01-01

    AIM: To investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer. METHODS: In our previous study of human whole-genome gene expression profiling, the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa. We found that MR-1 was associated with the location and differentiation of tumors. In this study, MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients. A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized, fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA. The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients. A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records. RESULTS: MR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues. MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238, P < 0.001) and protein levels (34.2% vs 13.2%, P = 0.003) in gastric cancer tissues. Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P = 0.034). Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group, and the difference was statistically significant (P = 0.002). Among all the patients with stage I-IV carcinoma, the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%, respectively, with respective median survival times

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

    PubMed

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

    2016-01-01

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

  4. 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

  5. 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.

  6. Current issues in human lead exposure and regulation of lead.

    PubMed

    Davis, J M; Elias, R W; Grant, L D

    1993-01-01

    Concern about lead as a significant public health problem has increased as epidemiological and experimental evidence has mounted regarding adverse health effects at successively lower levels of lead exposure. This concern has led to downward revision of criteria for acceptable blood lead concentrations to the 10 micrograms/dL mark now designated by EPA as a target level for regulatory development and enforcement/clean-up purposes. Much progress has been made in reducing lead exposures during the past 10-15 years, with marked declines evident both in air lead and blood lead concentrations in parallel to the phase-down of lead in gasoline and notable decreases in food lead exposure due to elimination of lead soldered cans by U.S. food processors. With the lessening of exposure from these sources, the importance of other components of multimedia exposure pathways has grown and stimulated increasing regulatory attention and abatement efforts to reduce health risks associated with lead exposure from drinking water, from lead-based paint, and from household dust and soil contaminated by deteriorating paint, smelter emissions, or various other sources. Increasing attention is also being accorded to reduction of occupational lead exposures (including those related to lead abatement activities), with particular concern for protection of men and women during their reproductive years.

  7. 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

  8. 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.

  9. 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.

  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. 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.

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

    PubMed

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

    2014-10-01

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

  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. ALARA and de minimis concepts in regulation of personnel exposure

    SciTech Connect

    Baum, J.W.

    1987-01-01

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

  15. Influence of environmental exposure on human epigenetic regulation

    PubMed Central

    Marsit, Carmen J.

    2015-01-01

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

  16. 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

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

    PubMed

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

    2016-04-01

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

  18. A proposed framework for consistent regulation of public exposures to radionuclides and other carcinogens

    SciTech Connect

    Kocher, D.C.; Hoffman, F.O.

    1991-01-01

    This paper discusses a proposed framework for consistent regulation of carcinogenic risks to the public based on establishing de manifestis (i.e., unacceptable) and de minimis (i.e., trivial) lifetime risks from exposure to any carcinogens at levels of about 10{sup {minus}1}--10{sup {minus}3} and 10{sup {minus}4}--10{sup {minus}6}, respectively, and reduction of risks above de minimis levels as low as reasonably achievable (ALARA). We then discuss certain differences in the way risks from exposure to radionuclides and other carcinogens currently are regulated or assessed which would need to be considered in implementing the proposed regulatory framework for all carcinogens.

  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. 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…

  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. 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.

  3. 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.

  4. Improved pH-dependent drug release and oral exposure of telmisartan, a poorly soluble drug through the formation of drug-aminoclay complex.

    PubMed

    Yang, Liang; Shao, Yating; Han, Hyo-Kyung

    2014-08-25

    Telmisartan (TEL) belongs to BCS class II (low solubility/high permeability) and exhibits the pH-dependent drug release. Since 3-aminopropyl functionalized magnesium phyllosilicate (aminoclay) can intercalate or adsorb the negatively charged molecules via the electrostatic interaction, TEL-aminoclay complex was synthesized to improve the pH dependent drug release and the oral exposure of TEL. Co-precipitation method was adopted to incorporate TEL into aminoclay with the variation of drug/aminoclay ratios, and then dissolution profiles of TEL from TEL-aminoclay complex were evaluated at different pHs. Structural characterization was performed by XRD, ATR-FTIR, and TEM, indicating the electrostatic interaction between TEL and the surface of the aminoclay lamellae. Furthermore, drug crystallinity was changed to an amorphous form via the molecular interactions between TEL and aminoclay. TEL exhibited rapid and complete dissolution at pH 1.2 within 15 min from all the tested formulations. However, while the untreated powder indicated negligible dissolution at pH 4 and pH 6.8, the formation of drug-clay complex significantly improved the dissolution rate as well as the extent of drug release at the higher pHs. In addition, following an oral administration of TEL-aminoclay, Cmax and AUC of TEL increased by about 8 and 5 fold respectively, while Tmax was shorten. The results suggest that formation of aminoclay complex should be promising to enhance the bioavailability of a poorly soluble drug, TEL.

  5. An empirical analysis of exposure-based regulation to abate toxic air pollution

    SciTech Connect

    Marakovits, D.M.; Considine, T.J.

    1996-11-01

    Title III of the 1990 Clean Air Act Amendments requires the Environmental Protection Agency to regulate 189 air toxics, including emissions from by-product coke ovens. Economists criticize the inefficiency of uniform standards, but Title III makes no provision for flexible regulatory instruments. Environmental health scientists suggest that population exposure, not necessarily ambient air quality, should motivate environmental air pollution policies. Using an engineering-economic model of the United States steel industry, we estimate that an exposure-based policy can achieve the same level of public health as coke oven emissions standards and can reduce compliance costs by up to 60.0%. 18 refs., 3 figs., 1 tab.

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

    PubMed

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

    2013-11-01

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

  7. 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

  8. 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.

  9. Met-regulated expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and aggressive phenotype

    PubMed Central

    Kaposi-Novak, Pal; Lee, Ju-Seog; Gòmez-Quiroz, Luis; Coulouarn, Cédric; Factor, Valentina M.; Thorgeirsson, Snorri S.

    2006-01-01

    Identification of specific gene expression signatures characteristic of oncogenic pathways is an important step toward molecular classification of human malignancies. Aberrant activation of the Met signaling pathway is frequently associated with tumor progression and metastasis. In this study, we defined the Met-dependent gene expression signature using global gene expression profiling of WT and Met-deficient primary mouse hepatocytes. Newly identified transcriptional targets of the Met pathway included genes involved in the regulation of oxidative stress responses as well as cell motility, cytoskeletal organization, and angiogenesis. To assess the importance of a Met-regulated gene expression signature, a comparative functional genomic approach was applied to 242 human hepatocellular carcinomas (HCCs) and 7 metastatic liver lesions. Cluster analysis revealed that a subset of human HCCs and all liver metastases shared the Met-induced expression signature. Furthermore, the presence of the Met signature showed significant correlation with increased vascular invasion rate and microvessel density as well as with decreased mean survival time of HCC patients. We conclude that the genetically defined gene expression signatures in combination with comparative functional genomics constitute an attractive paradigm for defining both the function of oncogenic pathways and the clinically relevant subgroups of human cancers. PMID:16710476

  10. 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

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

    PubMed

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

    2016-01-01

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

  12. 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

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

    PubMed Central

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

    2010-01-01

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

  15. Evolution of particulate regulation in China--prospects and challenges of exposure-based control.

    PubMed

    Florig, H Keith; Sun, Guodong; Song, Guojun

    2002-12-01

    China's urban and rural populations face very serious health risks from combustion particles. Major sources of exposure to inhalable particulates include the burning solid fuels (biomass and coal) for household cooking and heating, coal-fired industrial and residential boilers, tobacco smoking, and diesel motor vehicles. China began to address particulate pollution problems over 25 years ago and has implemented a series of progressively more aggressive policies. This paper reviews the successes and limitations of past and existing policies for particulate controls, as well as the effects of China's economic reforms and energy policies on particulate exposure and pollution management. We examine the challenge of emissions reporting, required as part of both China's pollution levy system and emerging system for "total emissions control." Finally, we discuss practical steps toward exposure-based regulation of particulates, which would take advantage of the high cost-effectiveness for lifesaving of controlling particulate exposure from household and neighborhood sources relative to that of controlling exposure from industrial sources.

  16. Exposure to fluorescent light triggers down regulation of genes involved with mitotic progression in Xiphophorus skin.

    PubMed

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

    2015-12-01

    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, and arntl1a) 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, and cdca7a) and chromosome segregation (e.g., cenpe, cenpf, cenpi, cenpk, cenpo, cenpp, and cenpu; cep70; knstrm, kntc, mcm2, mcm5; smc2). In addition, several DNA replication and recombination repair genes (e.g., pola1, pole, rec52, rad54l, rpa1, and parpbp) 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, and xrcc4). 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.

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

    PubMed

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

    2016-10-15

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

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

    PubMed Central

    Connell, Lauren E.; Francis, Lori A.

    2014-01-01

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

  19. Down-Regulated Phosphoglycerate Kinase 1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Cancer.

    PubMed

    Lu, Wei; Gao, Jian; Yang, Jingyun; Cao, Yang; Jiang, Lin; Li, Maolan; Zhang, Yijian; Zhou, Jian; Liu, Yingbin

    2015-12-01

    To evaluate prognostic significance of phosphoglycerate kinase 1 (PGK1) protein expression in patients with gallbladder cancer (GBC).Ninety-five patients who underwent surgical resection for GBC between January 2004 and December 2010 were enrolled. Overall survival (OS) and disease-free survival (DFS) were evaluated over a 10-year follow-up. PGK1 expression was assessed by tissue microarray and immunohistochemistry. Prognostic significance was analyzed using multivariate Cox regression.PGK1 was highly expressed in all gallbladder mucosa. Decreased PGK1 expression was detected in 54.7% (52/95) of patients with GBC. It was significantly down-regulated in GBC samples compared with that in gallbladder mucosa (P < 0.0001), and was associated with multiple clinicopathological factors. Multivariate survival analysis showed that low PGK1 expression was associated with shorter OS (median 12.8 vs 45.4 months; hazard ratio [HR] = 3.077; 95% confidence interval [CI], 1.373-6.897; P = 0.006) and DFS (median 8.3 vs 37.9 months; HR = 2.988; 95% CI, 1.315-6.790; P = 0.009), indicating that PGK1 expression was an independent prognostic factor in patients with GBC.Low PGK1 expression was associated with progression in patients with GBC. PGK1 expression could be a useful prognostic biomarker for GBC.

  20. 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.

  1. 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.

  2. Differential Regulation of the Period Genes in Striatal Regions following Cocaine Exposure

    PubMed Central

    Falcon, Edgardo; Ozburn, Angela; Mukherjee, Shibani; Roybal, Kole; McClung, Colleen A.

    2013-01-01

    Several studies have suggested that disruptions in circadian rhythms contribute to the pathophysiology of multiple psychiatric diseases, including drug addiction. In fact, a number of the genes involved in the regulation of circadian rhythms are also involved in modulating the reward value for drugs of abuse, like cocaine. Thus, we wanted to determine the effects of chronic cocaine on the expression of several circadian genes in the Nucleus Accumbens (NAc) and Caudate Putamen (CP), regions of the brain known to be involved in the behavioral responses to drugs of abuse. Moreover, we wanted to explore the mechanism by which these genes are regulated following cocaine exposure. Here we find that after repeated cocaine exposure, expression of the Period (Per) genes and Neuronal PAS Domain Protein 2 (Npas2) are elevated, in a somewhat regionally selective fashion. Moreover, NPAS2 (but not CLOCK (Circadian Locomotor Output Cycles Kaput)) protein binding at Per gene promoters was enhanced following cocaine treatment. Mice lacking a functional Npas2 gene failed to exhibit any induction of Per gene expression after cocaine, suggesting that NPAS2 is necessary for this cocaine-induced regulation. Examination of Per gene and Npas2 expression over twenty-four hours identified changes in diurnal rhythmicity of these genes following chronic cocaine, which were regionally specific. Taken together, these studies point to selective disruptions in Per gene rhythmicity in striatial regions following chronic cocaine treatment, which are mediated primarily by NPAS2. PMID:23776671

  3. 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.

  4. Resistance to freshwater exposure in White Sea Littorina spp. II: Acid-base regulation.

    PubMed

    Sokolova, I M; Bock, C; Pörtner, H O

    2000-03-01

    Parameters of acid-base and energy status were studied by in vivo 31P-nuclear magnetic resonance spectroscopy in three White Sea Littorina spp. (L. littorea, L. saxatilis and L. obtusata) during prolonged anaerobiosis in freshwater. Intracellular pH decreased significantly, especially during the early period of anaerobiosis, but later the decrease in intracellular pH slowed down considerably, suggesting a capacity for intracellular pH regulation in all three species. There was a trend for intracellular pH to fall most rapidly in the least freshwater-resistant species, L. obtusata, as compared to the most resistant, L. littorea. Non-bicarbonate, non-phosphate buffer values estimated by the homogenate technique were similar in the three studied species (28-37 mmol pH(-1) kg(-1) wet weight) and did not change during freshwater exposure. The CaCO3 buffer value of the foot tissues was considerably higher (171-218 mmol pH(-1) kg(-1) wet weight) and decreased significantly during freshwater exposure. The contribution of the multiple tissue buffering systems to intracellular pH regulation in Littorina spp. shifts between different stages of freshwater exposure. Initially, the non-bicarbonate, non-phosphate tissue buffering system seems to be of major importance for metabolic proton buffering at intracellular pH between 7.5 and 7.0. During later stages of anaerobiosis and at lower intracellular pH, the CaCO3 buffer is involved in proton buffering. Decrease in the CaCO3 buffer value during freshwater exposure was in quantitative agreement with the amount of metabolic protons buffered, thus suggesting that CaCO3 tissue stores may serve as a major buffering system during prolonged anaerobiosis in Littorina spp. PMID:10791570

  5. 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.

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

    PubMed

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

    2015-11-01

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

  7. Aberration in epigenetic gene regulation in hippocampal neurogenesis by developmental exposure to manganese chloride in mice.

    PubMed

    Wang, Liyun; Shiraki, Ayako; Itahashi, Megu; Akane, Hirotoshi; Abe, Hajime; Mitsumori, Kunitoshi; Shibutani, Makoto

    2013-11-01

    We have shown that maternal manganese (Mn) exposure caused sustained disruption of hippocampal neurogenesis of mouse offspring. To clarify the effects of maternal Mn exposure on epigenetic gene regulation contributing to the sustained disruption of hippocampal neurogenesis, we treated pregnant ICR mice with MnCl₂ in diet from gestational day 10 through day 21 after delivery on weaning and searched epigenetically downregulated genes by global promoter methylation analysis in the hippocampal dentate gyrus of male offspring on postnatal day (PND) 21 and PND 77. By CpG promoter microarray analysis on PND 21 following 800-ppm Mn exposure, sustained promoter hypermethylation and transcript downregulation through PND 77 were confirmed with Mid1, Atp1a3, and Nr2f1, whereas Pvalb showed a transient hypermethylation only on weaning. The numbers of Pvalb⁺ and ATP1a3⁺ neurons suggestive of γ-aminobutyric acid (GABA)ergic interneurons, Mid1⁺ cells suggestive of late-stage granule cell lineage and GABAergic interneurons, and COUP-TF1⁺ cells suggestive of early-stage granule cell lineage were all reduced on PND 21, and reductions were sustained on PND 77 except for no change in Pvalb⁺ cells. Mid1⁺ cells showed asymmetric distribution with right-side predominance, and Mn exposure abolished it by promoter hypermethylation of the right side. These findings indicate epigenetic mechanisms as mediators, through which Mn exposure modulates neurogenesis involving both granule cell lineage and GABAergic interneurons with long-lasting and stable repercussions. Disruption of asymmetric cellular distribution of Mid1 suggests that higher brain functions specialized in the left or right side of the brain were affected.

  8. 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.

  9. Regulation of plasminogen activator inhibitor-1 expression in endothelial cells with exposure to metal nanoparticles.

    PubMed

    Yu, Min; Mo, Yiqun; Wan, Rong; Chien, Sufan; Zhang, Xing; Zhang, Qunwei

    2010-05-19

    Recent studies demonstrated that exposure to nanoparticles could enhance the adhesion of endothelial cells and modify the membrane structure of vascular endothelium. The endothelium plays an important role in the regulation of fibrinolysis, and imbalance of the fibrinolysis system potential contributes to the development of thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is the most potent endogenous inhibitor of fibrinolysis and is involved in the pathogenesis of several cardiovascular diseases. The aim of this study was to investigate the alteration of PAI-1 expression in mouse pulmonary microvascular endothelial cells (MPMVEC) exposed to the metal nanoparticles that are known to be reactive, and the potential underlying mechanisms. We compared the alteration of PAI-1 expression in MPMVEC exposed to non-toxic doses of nano-size copper (II) oxide (Nano-CuO) and nano-size titanium dioxide (Nano-TiO(2)). Our results showed that Nano-CuO caused a dose- and time-dependent increase in PAI-1 expression. Moreover, exposure of MPMVEC to Nano-CuO caused reactive oxygen species (ROS) generation that was abolished by pre-treatment of cells with ROS scavengers or inhibitors, DPI, NAC and catalase. Exposure of MPMVEC to Nano-CuO also caused a dose- and time-dependent increase in p38 phosphorylation by Western blot. These effects were significantly attenuated when MPMVEC were pre-treated with DPI, NAC and catalase. To further investigate the role of p38 phosphorylation in Nano-CuO-induced PAI-1 overexpression, the p38 inhibitor, SB203580, was used to pre-treat cells prior to Nano-CuO exposure. We found that Nano-CuO-induced overexpression of PAI-1 was attenuated by p38 inhibitor pre-treatment. However, Nano-TiO(2) did not show the same results. Our results suggest that Nano-CuO caused up-regulation of PAI-1 in endothelial cells is mediated by p38 phosphorylation due to oxidative stress. These findings have important implications for understanding the potential health

  10. 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. PMID:26393763

  11. Ageing and the Regulation of Cell Activities during Exposure to Cold

    PubMed Central

    Finch, Caleb E.; Foster, Jeffrey R.; Mirsky, Alfred E.

    1969-01-01

    The inability to maintain body temperature and a selective pattern of changes in the regulation of cell activities were revealed by briefly exposing ageing C57B1/6J male mice to cold (10°C). The induction of liver tyrosine aminotransferase (TAT) during exposure to cold (a gene-dependent process) was markedly delayed in senescent mice (26 months old) as compared with younger mice (3–16 months old); after the delay, the rate of increase of TAT was similar to that prevailing in younger mice. Direct challenge of the liver with injections of corticosterone or insulin elicited the induction of TAT on an identical time course in young and senescent mice. These experiments provide an example of an age change in a gene-dependent cell process (the delayed induction of TAT in senescent mice during exposure to cold) which is not due to a change in the potential of the genome for responding when exogenous stimulae are supplied (injection of hormones). In contrast to the age-related change in liver cell activities, no significant changes were found in the secretion of corticosterone during exposure to cold. Although the seat of these selective age-related changes in the regulation of cell activities remains unclear, it is argued that generalized damage to the genome of cells throughout the body is not involved. The results of this and other studies showing the selective effect of age on cell activities are considered in terms of the concept that many cellular age changes represent the response of cells to primary age-related changes in humoral factors in the internal environment of the body. PMID:4391050

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. Exposure to Cocaine Dynamically Regulates the Intrinsic Membrane Excitability of Nucleus Accumbens Neurons

    PubMed Central

    Mu, Ping; Moyer, Jason T.; Ishikawa, Masago; Zhang, Yonghong; Panksepp, Jaak; Sorg, Barbara A.; Schlüter, Oliver M.; Dong, Yan

    2010-01-01

    Drug-induced malfunction of nucleus accumbens (NAc) neurons underlies a key pathophysiology of drug addiction. Drug-induced changes in intrinsic membrane excitability of NAc neurons are thought to be critical for producing behavioral alterations. Previous studies demonstrate that following short-term (2d) or long-term (21d) withdrawal from non-contingent cocaine injection, the intrinsic membrane excitability of NAc shell (NAcSh) neurons is decreased, and decreased membrane excitability of NAcSh neurons increases the acute locomotor response to cocaine. However, animals exhibit distinct cellular and behavioral alterations at different stages of cocaine exposure, suggesting that the decreased membrane excitability of NAc neurons may not be a persistent change. Here, we demonstrate that the membrane excitability of NAcSh neurons is differentially regulated depending on whether cocaine is administered contingently or non-contingently. Specifically, the membrane excitability of NAcSh MSNs was decreased at 2d after withdrawal from either 5-day intraperitoneal (i.p.) injections (15 mg/kg) or cocaine self-administration (SA). At 21d of withdrawal, the membrane excitability of NAcSh MSNs, which remained low in i.p.-pretreated rats, returned to a normal level in SA-pretreated rats. Furthermore, upon a re-exposure to cocaine after long-term withdrawal, the membrane excitability of NAcSh MSNs instantly returned to a normal level in i.p.-pretreated rats. On the other hand, in SA-pretreated rats, the re-exposure elevated the membrane excitability of NAcSh MSMs beyond the normal level. These results suggest that the dynamic alterations in membrane excitability of NAcSh MSNs, together with the dynamic changes in synaptic input, contribute differentially to the behavioral consequences of contingent and non-contingent cocaine administration. PMID:20220002

  17. 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

  18. Generation of a poor prognostic chronic lymphocytic leukemia-like disease model: PKCα subversion induces up-regulation of PKCβII expression in B lymphocytes

    PubMed Central

    Nakagawa, Rinako; Vukovic, Milica; Tarafdar, Anuradha; Cosimo, Emilio; Dunn, Karen; McCaig, Alison M.; Holroyd, Ailsa; McClanahan, Fabienne; Ramsay, Alan G.; Gribben, John G.; Michie, Alison M.

    2015-01-01

    Overwhelming evidence identifies the microenvironment as a critical factor in the development and progression of chronic lymphocytic leukemia, underlining the importance of developing suitable translational models to study the pathogenesis of the disease. We previously established that stable expression of kinase dead protein kinase C alpha in hematopoietic progenitor cells resulted in the development of a chronic lymphocytic leukemia-like disease in mice. Here we demonstrate that this chronic lymphocytic leukemia model resembles the more aggressive subset of chronic lymphocytic leukemia, expressing predominantly unmutated immunoglobulin heavy chain genes, with upregulated tyrosine kinase ZAP-70 expression and elevated ERK-MAPK-mTor signaling, resulting in enhanced proliferation and increased tumor load in lymphoid organs. Reduced function of PKCα leads to an up-regulation of PKCβII expression, which is also associated with a poor prognostic subset of human chronic lymphocytic leukemia samples. Treatment of chronic lymphocytic leukemia-like cells with the selective PKCβ inhibitor enzastaurin caused cell cycle arrest and apoptosis both in vitro and in vivo, and a reduction in the leukemic burden in vivo. These results demonstrate the importance of PKCβII in chronic lymphocytic leukemia-like disease progression and suggest a role for PKCα subversion in creating permissive conditions for leukemogenesis. PMID:25616575

  19. 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

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

    PubMed

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

    2016-01-01

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

  1. 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

  2. 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

  3. THE IMMIGRANT POOR AND THE RESIDUAL POOR.

    ERIC Educational Resources Information Center

    SEGALMAN, RALPH

    AN ANALYSIS OF THE LIVES OF THE POOR IN AMERICA WILL SHOW DIFFERENCES BETWEEN THE IMMIGRANT (AND REFUGEE) POOR AND THE RESIDUAL POOR (NEGROES, PUERTO RICANS, LATIN AMERICANS, INDIANS, AND OTHERS). THE IMMIGRANT POOR WERE ACCULTURATED AND ABSORBED INTO THE MAINSTREAM OF AMERICAN LIFE WITHIN THREE GENERATIONS, WHEREAS THE RESIDUAL POOR HAVE BEEN…

  4. 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.

  5. 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

  6. 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

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

    PubMed

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

    2009-09-01

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

  8. 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.

  9. 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.

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

    PubMed

    Ikeno, Tomoko; Yan, Lily

    2016-08-01

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

  11. 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

  12. Public Place Smoke-Free Regulations, Secondhand Smoke Exposure and Related Beliefs, Awareness, Attitudes, and Practices among Chinese Urban Residents

    PubMed Central

    Yang, Tingzhong; Abdullah, Abu S.; Li, Li; Rockett, Ian R. H.; Lin, Yan; Ying, Jun; Guo, Wei; Wu, Dan; Li, Mu

    2013-01-01

    Objective: To evaluate the association between smoke-free regulations in public places and secondhand smoke exposure and related beliefs, awareness, attitudes, and behavior among urban residents in China. Methods: We selected one city (Hangzhou) as the intervention city and another (Jiaxing) as the comparison. A structured self-administered questionnaire was used for data collection, and implemented at two time points across a 20-month interval. Both unadjusted and adjusted logistic methods were considered in analyses. Multiple regression procedures were performed in examining variation between final and baseline measures. Results: Smoke-free regulations in the intervention city were associated with a significant decline in personal secondhand smoke exposure in government buildings, buses or taxis, and restaurants, but there was no change in such exposure in healthcare facilities and schools. In terms of personal smoking beliefs, awareness, attitudes, and practices, the only significant change was in giving quitting advice to proximal family members. Conclusions: There was a statistically significant association between implementation of smoke-free regulations in a city and inhibition of secondhand tobacco smoking exposure in public places. However, any such impact was limited. Effective tobacco control in China will require comprehensive laws implemented fully and supported by penalties and a combination of strong public health education. PMID:23749054

  13. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-04-01

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

  17. 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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2012-01-01

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

  1. Prepubertal exposure to elevated manganese results in estradiol regulated mammary gland ductal differentiation and hyperplasia in female rats

    PubMed Central

    Dearth, Robert K; Hiney, Jill K; Srivastava, Vinod K; Hamilton, Alina M; Dees, William L

    2015-01-01

    Evidence suggests that environmental substances regulating estrogenic pathways during puberty may be detrimental to the developing mammary gland (MG). Manganese (Mn) is a trace mineral required for normal physiological processes. Prepubertal exposure to Mn induces precocious puberty in rats, an event associated with early elevations in puberty-related hormones, including estradiol (E2). However, until now the effect of Mn-induced precocious MG development has not been determined. Therefore, we assessed the ability of prepubertal Mn exposure to advance normal MG development and alter E2 driven pathways involved in tumorigenesis. Sprague Dawley female rats were gavaged daily with either 10 mg/kg manganese chloride (MnCl2) or saline (control) from postnatal day (PND) 12 through PND 30. Blood and MGs were collected on PNDs 30 and 120. Compared to controls, serum E2 levels on PND 30 were elevated (p<0.05) in the Mn-treated group. Mn exposure significantly increased differentiated MG terminal ductal structures and the percentage of MG epithelial cells that stained positive for the proliferative marker, Ki67, at PND 30 (p<0.001) and PND 120 (p < 0.001). Levels of Mn (ppm) were not elevated in these MGs. Mn-treated animals (40%) exhibited reactive stroma and intra-luminal focal hyperplasia in hemotoxylin and eosin stained MGs at PND 120. Furthermore, Mn exposure resulted in elevated protein expression levels of estrogen receptor α, activator protein 2α, phosphorylated (p)-Akt, and p53 in MGs on PND 120, but not on PND 30. Collectively, these data show that exposure to a supplemental dose of Mn causes accelerated pubertal MG growth which can progress to adult hyperplasia; thus, providing evidence that early life Mn exposure may increase susceptibility to breast cancer. PMID:24845367

  2. 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…

  3. Implications of uncertainty in exposure assessment for groundwater contamination

    USGS Publications Warehouse

    Reichard, Eric G.; Izbicki, John A.; Martin, Peter

    1995-01-01

    Decision-making on regulation, mitigation, and treatment of drinking water contamination depends, in part, on estimates of human exposure. Assessment of past, present and potential future exposure levels requires quantitative characterization of the contaminant sources, the transport of contaminants and the level of actual human exposure to the contaminated water. Failure to consider the uncertainties in these three components of exposure assessment can lead to poor decisions such as implementing an inappropriate mitigation strategy or failing to regulate an important contaminant. Three examples from US Geological Survey hydrogeologic studies in southern California are presented to illustrate some of the unique uncertainties associated with exposure assessment for groundwater contamination.

  4. Photosynthetic down-regulation under elevated CO₂ exposure can be prevented by nitrogen supply in nodulated alfalfa.

    PubMed

    Sanz-Sáez, Alvaro; Erice, Gorka; Aranjuelo, Iker; Nogués, Salvador; Irigoyen, Juan José; Sánchez-Díaz, Manuel

    2010-12-15

    Increasing atmospheric CO₂ concentrations are expected to enhance plant photosynthesis and yield. Nevertheless, after long-term exposure, plants acclimate and show a reduction in photosynthetic activity (called down-regulation), which may cause a reduction in potential yield. Some authors suggest that down-regulation is related to nutrient availability, and more specifically, to an insufficient plant C sink strength caused by limited N supply. In this paper, we tested whether or not N availability prevents down-regulation of photosynthesis in nodulated alfalfa plants (Medicago sativa L.). To do so, we examined the effect of the addition of different levels of NH₄NO₃ (0, 10, and 15 mM) to 30-day-old nodulated alfalfa plants exposed to ambient (approximately 400 μmol mol⁻¹) or elevated CO₂ (700 μmol mol⁻¹) during a period of 1 month in growth chambers. After 2 weeks of exposure to elevated CO₂, no significant differences were observed in plant growth or photosynthesis rates. After 4 weeks of treatment, exclusively N₂ fixing alfalfa plants (0 mM NH₄NO₃) showed significant decreases in photosynthesis and Vc(max). Photosynthetic down-regulation of these plants was caused by the C/N imbalance as reflected by the carbohydrate and N data. On the other hand, plants supplied with 15 mM NH₄NO₃ grown under elevated CO₂ maintained high photosynthetic rates owing to their superior C/N adjustment. The intermediate N treatment, 10 mM NH₄NO₃, also showed photosynthetic down-regulation, but to a lesser degree than with 0 mM treatment. The present study clearly shows that external N supply can reduce or even avoid acclimation of photosynthesis to elevated CO₂ as a consequence of the increase in C sink strength associated with N availability.

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

    PubMed Central

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

    2015-01-01

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

  6. 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...

  7. Expression of 14-3-3 transcript isoforms in response to ethanol exposure and their regulation by miRNAs.

    PubMed

    Mathew, Divya Elizabeth; Larsen, Kaitlyn; Janeczek, Paulina; Lewohl, Joanne M

    2016-09-01

    The 14-3-3 proteins are a family of highly conserved molecular chaperones involved in the regulation of a number of key cellular functions including metabolism, stress response, protein trafficking, cell-cycle control, signal transduction, transcription, apoptosis and neurotransmission. 14-3-3 proteins have also been implicated in the pathophysiology of neurodegenerative disorders including Alzheimer disease and Parkinson disease. Recent studies have also shown that 14-3-3s are differentially expressed in the frontal cortex of human alcoholics suggesting a potential role in the pathophysiology of alcohol use disorders. Here we measured the expression of 14-3-3 transcripts in HEK293T cells in response to chronic ethanol treatment. Five of the seven transcripts (14-3-3β, 14-3-3γ, 14-3-3ζ, 14-3-3ε and 14-3-3θ) were significantly down-regulated following chronic exposure to ethanol for a five day period with these changes persisting even after withdrawal from ethanol treatment. One transcript, 14-3-3σ, was significantly up-regulated following chronic ethanol exposure and 14-3-3η showed no differences in expression in the same treatment model. The pattern of expression changes is similar to those seen in the frontal cortex of human alcoholics. To investigate the role of miRNAs in mediating the expression changes we measured the expression of the 14-3-3 transcripts following transfection with miR-203, miR-144 and miR-7 mimics. Although these miRNAs had predicted target sites in the 3'untranslated region of each 14-3-3 isoform, only miR-203 resulted in a down-regulation of 14-3-3θ transcript. In addition, the expression of 14-3-3γ was upregulated following transfection with miR-7 and miR-144 mimics. MiRNA regulation of these isoforms following alcohol exposure may lead to alterations in neurotransmission, the balance between cell survival and cell death, as well as changing the rewarding effects of alcohol. PMID:27370936

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

    SciTech Connect

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

    1986-01-01

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

  9. 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.

  10. Cardiac Repolarization and Autonomic Regulation during Short-Term Cold Exposure in Hypertensive Men: An Experimental Study

    PubMed Central

    Hintsala, Heidi; Kenttä, Tuomas V.; Tulppo, Mikko; Kiviniemi, Antti; Huikuri, Heikki V.; Mäntysaari, Matti; Keinänen-Kiukaannemi, Sirkka; Bloigu, Risto; Herzig, Karl-Heinz; Antikainen, Riitta; Rintamäki, Hannu; Jaakkola, Jouni J. K.; Ikäheimo, Tiina M.

    2014-01-01

    Objectives The aim of our study was to assess the effect of short-term cold exposure, typical in subarctic climate, on cardiac electrical function among untreated middle-aged hypertensive men. Methods We conducted a population-based recruitment of 51 hypertensive men and a control group of 32 men without hypertension (age 55–65 years) who underwent whole-body cold exposure (15 min exposure to temperature −10°C, wind 3 m/s, winter clothes). Conduction times and amplitudes, vectorcardiography, arrhythmias, and heart rate variability (autonomic nervous function) were assessed. Results Short-term cold exposure increased T-peak to T-end interval from 67 to 72 ms (p<0.001) and 71 to 75 ms (p<0.001) and T-wave amplitude from 0.12 to 0.14 mV (p<0.001) and from 0.17 to 0.21 mV (p<0.001), while QTc interval was shortened from 408 to 398 ms (p<0.001) and from 410 to 401 ms (p<0.001) among hypertensive men and controls, respectively. Cold exposure increased both low (from 390 to 630 ms2 (p<0.001) and 380 to 700 ms2 (p<0.001), respectively) and high frequency heart rate variability (from 90 to 190 ms2 (p<0.001) and 150 to 300 ms2 (p<0.001), respectively), while low-to-high frequency-ratio was reduced. In addition, the frequency of ventricular ectopic beats increased slightly during cold exposure. The cold induced changes were similar between untreated hypertensive men and controls. Conclusions Short-term cold exposure with moderate facial and mild whole body cooling resulted in prolongation of T-peak to T-end interval and higher T-wave amplitude while QTc interval was shortened. These changes of ventricular repolarization may have resulted from altered cardiac autonomic regulation and were unaffected by untreated hypertension. Trial Registration ClinicalTrials.gov NCT02007031 PMID:24983379

  11. MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis

    PubMed Central

    Li, Heng; Chen, Ke; Yu, Gan; Hu, Junhui; Tang, Kun; Zhou, Hui; Huang, Qihong; Li, Anping; Li, Yi; Ye, Zhangqun; Wang, Ji; Xu, Hua

    2015-01-01

    MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of noncoding RNAs. Here, we focused on the function and molecular mechanism of miR-1 and its potential clinical application in clear cell renal cell carcinoma (ccRCC). First, miR-1 was significantly downregulated in 87.8% renal cancer samples compared with corresponding noncancerous tissues (NCT), which was significantly associated with clinical stage, T classification and poor overall survival. Functional study demonstrated that enforced overexpression of miR-1 in renal cancer cells inhibited proliferation and metastasis in vitro and in vivo. Conversely, miR-1 inhibitor silencing miR-1 expression promoted cell proliferation and metastasis in ccRCC. CDK4, CDK6, Caprin1 and Slug were each directly targeted for inhibition by miR-1 and restoring their expression reversed miR-1-mediated inhibition of cell cycle progression and metastasis. Taken together, our findings established a tumor suppressive role for miR-1 in the progression of ccRCC by targeting CDK4, CDK6, Caprin1 and Slug and suggested miR-1 can be served as a novel potential therapeutic target for ccRCC. PMID:26036633

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

    PubMed

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

    2016-09-01

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

  13. Decreased expression of long non-coding RNA GAS5 indicates a poor prognosis and promotes cell proliferation and invasion in hepatocellular carcinoma by regulating vimentin

    PubMed Central

    CHANG, LEI; LI, CUICUI; LAN, TIAN; WU, LONG; YUAN, YUFENG; LIU, QUANYAN; LIU, ZHISU

    2016-01-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are key in carcinogenesis. The aim of the present study was to investigate the role of lncRNA GAS5 in HCC tissues and to define the role of growth arrest-specific 5 (GAS5) in the regulation of hepatoma cell proliferation, invasion and apoptosis. Quantitative polymerase chain reaction and in situ hybridization were performed to investigate the expression of GAS5 in tumor tissues and corresponding adjacent tissues from 50 patients with HCC. Low expression of GAS5 was significantly correlated with differentiation (P<0.010) and portal vein tumor thrombosis (P=0.001). Multivariate analysis indicated that GAS5 expression was an independent predictor for overall survival (P=0.017). Further experiments demonstrated that overexpression of GAS5 significantly suppressed the proliferation and invasion of hepatoma cells in vitro. Overexpression of GAS5 significantly promoted the apoptosis of hepatoma cells. In addition, it was demonstrated that GAS5 negatively regulates vimentin expression in vitro and in vivo. Notably, vimentin knockdown promoted GAS5-pcDNA3.1-inhibition of hepatoma cell proliferation. In conclusion, the present study suggests an important role of GAS5 in the molecular etiology of HCC and suggests the potential application of GAS5 in HCC therapy. PMID:26707238

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

    PubMed

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

    2001-12-01

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

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

    PubMed

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

    2001-12-01

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

  16. 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.

  17. 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.

  18. 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...

  19. 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…

  20. Sterilizing the Poor

    ERIC Educational Resources Information Center

    Rothman, Sheila M.

    1977-01-01

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

  1. Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism.

    PubMed

    Hao, Qin; Yadav, Rachita; Basse, Astrid L; Petersen, Sidsel; Sonne, Si B; Rasmussen, Simon; Zhu, Qianhua; Lu, Zhike; Wang, Jun; Audouze, Karine; Gupta, Ramneek; Madsen, Lise; Kristiansen, Karsten; Hansen, Jacob B

    2015-03-01

    We applied digital gene expression profiling to determine the transcriptome of brown and white adipose tissues (BAT and WAT, respectively) during cold exposure. Male C57BL/6J mice were exposed to cold for 2 or 4 days. A notable induction of genes related to glucose uptake, glycolysis, glycogen metabolism, and the pentose phosphate pathway was observed in BAT from cold-exposed animals. In addition, glycerol-3-phosphate dehydrogenase 1 expression was induced in BAT from cold-challenged mice, suggesting increased synthesis of glycerol from glucose. Similarly, expression of lactate dehydrogenases was induced by cold in BAT. Pyruvate dehydrogenase kinase 2 (Pdk2) and Pdk4 were expressed at significantly higher levels in BAT than in WAT, and Pdk2 was induced in BAT by cold. Of notice, only a subset of the changes detected in BAT was observed in WAT. Based on changes in gene expression during cold exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating triacylglycerol synthesis/fatty acid re-esterification; 3) glycogen turnover and lactate production are increased; and 4) entry of glucose carbon into the tricarboxylic acid cycle is restricted by PDK2 and PDK4. In summary, our results demonstrate extensive and diverse gene expression changes related to glucose handling in activated BAT. PMID:25516548

  2. 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

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

    PubMed

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

    1992-09-01

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

  4. Effects of subchronic samarium exposure on the histopathological structure and apoptosis regulation in mouse testis.

    PubMed

    Zhang, De-Yong; Shen, Xiu-Ying; Ruan, Qin; Xu, Xiao-Lu; Yang, San-Ping; Lu, Yin; Xu, Hui-Ying; Hao, Fei-Lin

    2014-03-01

    To evaluate the reproductive toxicity of samarium, a widely used rare earth element, male ICR mice were orally exposed to samarium nitrate for 90 days for lesion evaluation in the testis. Decreased organ coefficients, disorganized seminiferous tubules, and decreased spermatogenic cells and sperm of the testis were observed extensively in the treated groups, indicating that the testis is a target organ of samarium. Electron microscopy confirmed that the lesions inside the spermatogenic cells and sperm mainly included mitochondrial swelling, mitochondrial vacuolization, fuzzy nuclear membranes, and marginated chromatin. Increased spermatogenic cell apoptosis rate in the testis was confirmed with a TUNEL assay. And expression up-regulation of p53 and Bax, and down-regulation of Bcl-2 were observed (p<0.05), indicating the apoptosis is related to p53 mediated pathway. PMID:24561534

  5. 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.

  6. Skills training in affective and interpersonal regulation followed by exposure: a phase-based treatment for PTSD related to childhood abuse.

    PubMed

    Cloitre, Marylene; Koenen, Karestan C; Cohen, Lisa R; Han, Hyemee

    2002-10-01

    Fifty-eight women with posttraumatic stress disorder (PTSD) related to childhood abuse were randomly assigned to a 2-phase cognitive-behavioral treatment or a minimal attention wait list. Phase 1 of treatment included 8 weekly sessions of skills training in affect and interpersonal regulation; Phase 2 included 8 sessions of modified prolonged exposure. Compared with those on wait list, participants in active treatment showed significant improvement in affect regulation problems, interpersonal skills deficits, and PTSD symptoms. Gains were maintained at 3- and 9-month follow-up. Phase 1 therapeutic alliance and negative mood regulation skills predicted Phase 2 exposure success in reducing PTSD, suggesting the value of establishing a strong therapeutic relationship and emotion regulation skills before exposure work among chronic PTSD populations.

  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. 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.

  9. Synergistic induction of AHR regulated genes in developmental toxicity from co-exposure to two model PAHs in zebrafish

    PubMed Central

    Timme-Laragy, Alicia. R.; Cockman, Crystal. J.; Matson, Cole. W.; Di Giulio, Richard. T.

    2007-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are pollutants created by the incomplete combustion of carbon, and are increasing in the environment largely due to the burning of fossil fuels. PAHs occur as complex mixtures, and some combinations have been shown to cause synergistic developmental toxicity in fish embryos, characterized by pericardial edema and craniofacial malformations. Previous studies have indicated that in the zebrafish model, this toxicity is mediated by the aryl hydrocarbon receptor 2 (AHR2), and enhanced by inhibition of CYP1A activity. In this study, we further examined this interaction of the model PAH and AHR agonist β-naphthoflavone (BNF) with and without the AHR partial agonist/antagonist and CYP1A inhibitor α-naphthoflavone (ANF) to determine 1) whether ANF was acting as an AHR antagonist, 2) what alterations BNF and ANF both alone and in combination had on mRNA expression of the AHR regulated genes cytochrome P450 (cyp) 1a, 1b1, and 1c1, and the AHR repressor (ahrr2) prior to vs. during deformity onset, and 3) compare CYP1A enzyme activity with mRNA induction. Zebrafish embryos were exposed from 24–48 or 24–96 hpf to BNF, 1–100 μg/L, ANF, 1–150 μg/L, a BNF+ANF co-exposure (1 μg/L + 100 μg/L), or a DMSO solvent control. RNA was extracted and examined by quantitative real time PCR. Both BNF and ANF each individually resulted in a dose dependent increase CYP1A, CYP1B1, CYP1C1, and AHRR2 mRNA, confirming their activities as AHR agonists. In the BNF+ANF co-exposures prior to deformity onset, expression of these genes was synergistic, and expression levels of the AHR regulated genes resembled the higher doses of BNF alone. Gene induction during deformities was also significantly increased in the co-exposure, but to a lesser magnitude than prior to deformity onset. EROD measurements of CYP1A activity showed ANF inhibited activity induction by BNF in the co-exposure group; this finding is not predicted by mRNA expression, which is

  10. 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.

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

    PubMed

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

    2014-08-17

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

  12. Regulation of Glucose Transporter Expression in Human Intestinal Caco-2 Cells following Exposure to an Anthocyanin-Rich Berry Extract

    PubMed Central

    Alzaid, Fawaz; Cheung, Hoi-Man; Preedy, Victor R.; Sharp, Paul A.

    2013-01-01

    Polyphenols contained within plant tissues are consumed in significant amounts in the human diet and are known to influence a number of biological processes. This study investigated the effects of an anthocyanin-rich berry-extract on glucose uptake by human intestinal Caco-2 cells. Acute exposure (15 min) to berry extract (0.125%, w/v) significantly decreased both sodium-dependent (Total uptake) and sodium-independent (facilitated uptake) 3H-D-glucose uptake. In longer-term studies, SGLT1 mRNA and GLUT2 mRNA expression were reduced significantly. Polyphenols are known to interact directly with glucose transporters to regulate the rate of glucose absorption. Our in vitro data support this mechanism and also suggest that berry flavonoids may modulate post-prandial glycaemia by decreasing glucose transporter expression. Further studies are warranted to investigate the longer term effects of berry flavonoids on the management of glycaemia in human volunteers. PMID:24236070

  13. Corticosterone-regulated actions in the rat brain are affected by perinatal exposure to low dose of bisphenol A.

    PubMed

    Poimenova, A; Markaki, E; Rahiotis, C; Kitraki, E

    2010-05-19

    The estrogen-mimicking endocrine disrupter bisphenol A (BPA) which is used in the manufacture of plastic and epoxy resins, is one of the world's most heavily produced synthetic chemicals. BPA is detected in animal tissues, and its bio-accumulation has shown to be higher in the fetus than the mother. Exposure to doses below the daily safe limit has been reported to affect the sexual differentiation of the brain and modify the behavior of the exposed rodent offspring. The aim of the present study was to investigate in the rat the possible organizational effects of low BPA exposure on glucocorticoid-regulated responses. Female breeders were exposed to 40 microg/kg b.w. BPA daily throughout pregnancy and lactation. Plasma corticosterone levels and the two types of hippocampal corticosteroid receptors (GR and MR) were determined in mid-adolescent offspring under basal conditions and following a Y-maze task. BPA treated females had higher corticosterone levels than control females and BPA males and lower GR levels than BPA males, under basal conditions. Following the mildly stressful experience of Y-maze, corticosterone levels were increased in BPA-treated animals of both sexes, compared to the controls. GR levels were also increased in BPA-treated females compared to males. No effect of BPA was observed on MR levels, whereas the Y-maze experience significantly decreased receptors' levels in both female groups. The animals' performance in the task was also evaluated. BPA exposure significantly impaired the spatial recognition memory in both sexes, and modified the behavioural coping in a sex-dependent manner. Female BPA-treated offspring exhibited increased "anxiety-like" behaviour and dramatic loss of exploration attitude during the task, in comparison to males. This study provides for the first time evidence that corticosterone and its actions in the brain are sensitive to the programming effects of BPA at a dose below the currently acceptable daily intake. PMID

  14. Sgk1 regulates desmoglein 1 expression levels in oligodendrocytes in the mouse corpus callosum after chronic stress exposure.

    PubMed

    Miyata, Shingo; Yoshikawa, Keiko; Taniguchi, Manabu; Ishikawa, Toshiko; Tanaka, Takashi; Shimizu, Shoko; Tohyama, Masaya

    2015-08-14

    Major depression, one of the most prevalent mental illnesses, is thought to be a multifactorial disease related to both genetic and environmental factors. However, the genes responsible for and the pathogenesis of major depression at the molecular level remain unclear. Recently, we reported that stressed mice with elevated plasma corticosterone levels show upregulation and activation of serum glucocorticoid-regulated kinase (Sgk1) in oligodendrocytes. Active Sgk1 causes phosphorylation of N-myc downstream-regulated gene 1 (Ndrg1), and phospho-Ndrg1 increases the expression of N-cadherin, α-catenin, and β-catenin in oligodendrocytes. This activation of the Sgk1 cascade results in morphological changes in the oligodendrocytes of nerve fiber bundles, such as those present in the corpus callosum. However, little is known about the molecular functions of the traditional and/or desmosomal cadherin superfamily in oligodendrocytes. Therefore, in this study, we aimed to elucidate the functions of the desmosomal cadherin superfamily in oligodendrocytes. Desmoglein (Dsg) 1, Dsg2, and desmocollin 1 (Dsc1) were found to be expressed in the corpus callosum of mouse brain, and the expression of a subtype of Dsg1, Dsg1c, was upregulated in oligodendrocytes after chronic stress exposure. Furthermore, Dsg1 proteins were localized around the plasma membrane regions of oligodendrocytes. A study in primary oligodendrocyte cultures also revealed that chronic upregulation of Sgk1 by dexamethasone administration is involved in upregulation of Dsg1c mRNA. These results may indicate that chronic stress induced Sgk1 activation in oligodendrocytes, which increases Dsg1 expression near the plasma membrane. Thus, Dsg1 upregulation may be implicated in the molecular mechanisms underlying the morphological changes in oligodendrocytes in response to chronic stress exposure. PMID:26043694

  15. HPA function in adolescence: role of sex hormones in its regulation and the enduring consequences of exposure to stressors.

    PubMed

    McCormick, Cheryl M; Mathews, Iva Z

    2007-02-01

    The hypothalamic-pituitary-adrenal (HPA) axis is one of the physiological systems involved in coping with stressors. There are functional shifts in the HPA axis and its regulation by sex hormones over the lifespan that allow the animal to meet the challenges of the internal and external environment that are specific to each stage of development. Sex differences in HPA function emerge over adolescence, a phenomenon reflecting the concomitant initiation of regulatory effects of sex hormones. The focus of this review is recent research on differences between adolescents and adults in HPA function and the enduring effects of exposure to stressors in adolescence. During adolescence, HPA function is characterized by a prolonged activation in response to stressors compared to adulthood, which may render ongoing development of the brain vulnerable. Although research has been scarce, there is a growing evidence that exposure to stressors in adolescence may alter behavioural responses to drugs and cognitive performance in adulthood. However, the effects reported appear to be stressor-specific and sex-specific. Such research may contribute toward understanding the increased risk for drug abuse and psychopathology that occurs over adolescence in people.

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

    PubMed

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

    2015-03-01

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

  17. 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.

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

    PubMed

    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/Ca(2+) 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 [Ca(2+)]i fluorescence and vasoconstriction testing showed reduced Ca(2+), leading to diminished BKCa activation via ryanodine receptor Ca(2+) 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

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

    PubMed

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

    2015-08-17

    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/Ca(2+) 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 [Ca(2+)]i fluorescence and vasoconstriction testing showed reduced Ca(2+), leading to diminished BKCa activation via ryanodine receptor Ca(2+) 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.

  20. 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…

  1. 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.

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

    PubMed

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

    2016-09-01

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

  3. Regulation of cell cycle components during exposure to anoxia or dehydration stress in the wood frog, Rana sylvatica.

    PubMed

    Roufayel, Rabih; Biggar, Kyle K; Storey, Kenneth B

    2011-10-01

    The wood frog (Rana sylvatica) exhibits a well-developed natural anoxia and dehydration tolerance. The degree of stress tolerance depends on numerous biochemical adaptations, including stress-induced hypometabolism that helps to preserve long-term viability by reducing ATP demand. We hypothesized that the mechanisms involved in cell cycle control could act to aid in the establishment of the hypometabolic state required for stress survival. Selected proteins involved in the proliferation of cells were evaluated using immunoblotting in liver and skeletal muscle of wood frogs comparing controls with animals subjected to either 24-hr anoxia exposure under a nitrogen gas atmosphere or dehydration to 40% of total body water lost (all at 5°C). Levels of cyclins (type A, B, D, and E) decreased significantly under both stresses in liver and skeletal muscle. Similar reductions were seen for Cyclin-dependant kinases (Cdk) types 2, 4, and 6 in both liver and skeletal muscle; however, an increase in the relative amount of phosphorylated inactive p-Cdk (Thr14/Tyr15) was observed in liver under both stresses. Levels of positive regulators of Cdk activity (Cdc25 type A and C) were significantly reduced in both tissues under both stresses, whereas negative regulators of Cdk activity (p16(INK4a) and p27(KIP1) ) increased significantly in liver under both anoxia and dehydration stress (but not in muscle). This study provides the first report of differential regulation of cell cycle components in an anoxia and dehydration tolerant vertebrate, the wood frog, suggesting that cell cycle suppression is an active part of stress resistance and life extension in hypometabolic states.

  4. 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

  5. Poorly controlled gout: who is doing poorly?

    PubMed

    Chia, Faith Li-Ann

    2016-08-01

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

  6. 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.

  7. A proposed approach to regulating contaminated soil: identify safe concentrations for seven of the most frequently encountered exposure scenarios.

    PubMed

    Paustenbach, D J; Jernigan, J D; Bass, R; Kalmes, R; Scott, P

    1992-08-01

    Since 1980, more than 10,000 sites in the United States have been shown to contain soil which has elevated concentrations of various xenobiotics. Since that time, guidelines for deciding whether the level of contamination is worthy of concern have been proposed or promulgated by dozens of local, state, and federal regulatory agencies. Unfortunately, there has been little consistency in the guidelines suggested for each soil contaminant. For example, (a) the basis or rationale for some of the cleanup levels is unclear, (b) approaches to setting cleanup levels vary between states and agencies, (c) cleanup objectives often vary among agencies within the same state, and (d) the cleanup levels are usually set in a scientifically haphazard manner. This paper proposes that the most cost-effective and efficient way to quickly regulate contaminated soil is to establish "safe" concentrations for each chemical for the seven most common exposure scenarios. These exposure scenarios include (1) residential, (2) industrial, (3) agricultural, (4) recreational, (5) groundwater, (6) wildlife and aquatic species, and (7) runoff/erosion of particulates to waterways. The scientific approach and rationale for calculating the cleanup criteria are illustrated by evaluating dioxin and benzene, toluene, and xylene (BTX). The methods suggested here indicate that levels of dioxin of 25 and 50 ppb in residential and industrial soils, respectively, should be acceptable. The predominant concern for the agricultural and recreational scenarios is the runoff of particulates to waterways. For BTX, benzene will dictate the degree of cleanup and the primary hazard at most residential sites will be the inhalation of vapors. Benzene concentrations of 2.5, 14, and 250 ppm should be acceptable for residential, industrial, and recreational soils, respectively. Depending on the depth to groundwater and aquifer use, protection of groundwater may be the driving concern for establishing BTX cleanup levels and

  8. A proposed approach to regulating contaminated soil: identify safe concentrations for seven of the most frequently encountered exposure scenarios

    SciTech Connect

    Paustenbach, D.J.; Jernigan, J.D.; Bass, R.; Kalmes, R.; Scott, P. )

    1992-08-01

    Since 1980, more than 10,000 sites in the United States have been shown to contain soil which has elevated concentrations of various xenobiotics. Since that time, guidelines for deciding whether the level of contamination is worthy of concern have been proposed or promulgated by dozens of local, state, and federal regulatory agencies. Unfortunately, there has been little consistency in the guidelines suggested for each soil contaminant. For example, (a) the basis or rationale for some of the cleanup levels is unclear, (b) approaches to setting cleanup levels vary between states and agencies, (c) cleanup objectives often vary among agencies within the same state, and (d) the cleanup levels are usually set in a scientifically haphazard manner. This paper proposes that the most cost-effective and efficient way to quickly regulate contaminated soil is to establish safe' concentrations for each chemical for the seven most common exposure scenarios. These exposure scenarios include (1) residential, (2) industrial, (3) agricultural, (4) recreational, (5) groundwater, (6) wildlife and aquatic species, and (7) runoff/erosion of particulates to waterways. The scientific approach and rationale for calculating the cleanup criteria are illustrated by evaluating dioxin and benzene, toluene, and xylene (BTX). The methods suggested here indicate that levels of dioxin of 25 and 50 ppb in residential and industrial soils, respectively, should be acceptable. The predominant concern for the agricultural and recreational scenarios is the runoff of particulates to waterways. For BTX, benzene will dictate the degree of cleanup and the primary hazard at most residential sites will be the inhalation of vapors. Benzene concentrations of 2.5, 14, and 250 ppm should be acceptable for residential, industrial, and recreational soils, respectively.126 references.

  9. Nicotinic acetylcholine receptors containing alpha 7 subunits on rat cortical neurons do not undergo long-lasting inactivation even when up-regulated by chronic nicotine exposure.

    PubMed

    Kawai, H; Berg, D K

    2001-09-01

    Chronic exposure to (-)nicotine has been widely reported to up-regulate nicotinic acetylcholine receptors on neurons and induce long-term inactivation as a possible cause. Nicotinic receptors containing alpha 7 subunits are among the most abundant in brain and influence diverse cellular events. Whole-cell patch clamp recording from embryonic rat cortical neurons in culture was used to identify responses from alpha 7-containing receptors. Immunochemical staining for glutamic acid decarboxylase (GAD) indicated that both GABAergic and non-GABAergic neurons expressed the receptors. Exposure to micromolar concentrations of nicotine for 1-4 days caused up-regulation of the receptors as measured by [alpha-(125)I]-bungarotoxin binding. Carbachol produced the same up-regulation, and cell counts demonstrated that neuronal survival was unchanged. The up-regulation was accompanied by an increased whole-cell response; no evidence was found for long-lasting inactivation. Autonomic alpha 7-containing receptors also avoided long-lasting inactivation, even though the receptors were down-regulated by nicotine. Blocking protein synthesis or protein glycosylation prevented receptor up-regulation on cortical neurons, suggesting that new synthesis was required. No evidence was found for a pre-existing intracellular pool that supplied receptors to the surface. The results indicate that alpha 7-containing receptors differ from other receptor subtypes in their regulation by nicotine and demonstrate further that long-lasting inactivation is not an obligatory requirement for up-regulation in this case.

  10. 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)...

  11. 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 Central

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

    2011-01-01

    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. PMID:21556189

  12. 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.

  13. 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. PMID:21556189

  14. Intratracheal exposure to Fab fragments of an allergen-specific monoclonal antibody regulates asthmatic responses in mice

    PubMed Central

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

    2014-01-01

    Fab fragments (Fabs) maintain the ability to bind to specific antigens but lack effector functions due to the absence of the Fc portion. In the present study, we tested whether Fabs of an allergen-specific monoclonal antibody (mAb) were able to regulate asthmatic responses in mice. Asthmatic responses were induced in BALB/c mice by passive sensitization with anti-ovalbumin (OVA) polyclonal antibodies (pAbs) (day 0) and by active sensitization with OVA (days 0 and 14), followed by intratracheal (i.t.) challenge with OVA on day 1 and days 28, 29, 30 and 35. Fabs prepared by the digestion of an anti-OVA IgG1 (O1-10) mAb with papain were i.t. administered only once 30 min before antigenic challenge on day 1 or day 35. The results showed that i.t. administration of O1-10 Fabs with OVA markedly suppressed the early and/or late phases of asthmatic responses caused by passive and active sensitization. Similar results were obtained when Fabs of anti-OVA IgG2b mAb (O2B-3) were i.t. administered. In contrast, neither i.t. injection of intact 01-10/O2B-3 nor systemic injection of O1-10 Fabs suppressed the asthmatic responses. In vitro studies revealed that the capture of OVA by O1-10 Fabs prevented the subsequent binding of intact anti-OVA pAbs to the captured OVA. These results suggest that asthmatic responses may be down-regulated by the i.t. exposure to Fabs of an allergen-specific mAb via a mechanism involving the capture of allergen by Fabs in the respiratory tract before the interaction of intact antibody and allergen essential for the induction of asthmatic responses. PMID:24303921

  15. 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.

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

    PubMed Central

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

    2015-01-01

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

  17. Decreased expression of the long non-coding RNA FENDRR is associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectin1 expression

    PubMed Central

    2014-01-01

    Background FENDRR is a long non-coding RNAs (lncRNA) that binds to polycomb repressive complexe 2 (PRC2) to epigenetically regulate the expression of its target gene. The clinical role of FENDRR in carcinomas remains yet to be found. Method Real-time polymerase chain reaction (PCR) was used to examine FENDRR expression in gastric cancer cell lines/tissues compared with normal epithelial cells/adjacent non-tumorous tissues. Cell proliferation assays, Wound healing assays, and in vitro and in vivo invasion and migration assays were performed to detect the biological effects of FENDRR in gastric cancer cells. Real-time PCR, western-blot and immunohistochemistry were used to evaluate the mRNA and protein expression of fibronectin1 (FN1). Secreted matrix metalloproteinase (MMP) activities were detected and characterized using gelatin zymography assay. Results FENDRR was downregulated in gastric cancer cell lines and cancerous tissues, as compared with normal gastric epithelial cells and adjacent noncancerous tissue samples. Low FENDRR expression was correlated with deeper tumor invasion (p < 0.001), higher tumor stage (p = 0.001), and lymphatic metastasis (p = 0.007). Univariate and multivariate analyses indicated that low FENDRR expression predicted poor prognosis. Histone deacetylation was involved in the downregulation of FENDRR in gastric cancer cells. FENDER overexpression suppressed invasion and migration by gastric cancer cells in vitro, by downregulating FN1 and MMP2/MMP9 expression. Conclusion Low expression of the lncRNA FENDRR occurs in gastric cancer and is associated with poor prognosis. Thus, FENDRR plays an important role in the progression and metastasis of gastric cancer. PMID:25167886

  18. Poor school performance.

    PubMed

    Karande, Sunil; Kulkarni, Madhuri

    2005-11-01

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

  19. Morphosyntax in Poor Comprehenders

    ERIC Educational Resources Information Center

    Adlof, Suzanne M.; Catts, Hugh W.

    2015-01-01

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

  20. 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

  1. 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.

  2. [Poor prognosis childhood cancers].

    PubMed

    Valteau-Couanet, Dominique; Minard, Véronique

    2007-05-31

    Poor prognosis childhood cancers are mainly metastatic diseases represented by stage IV neuroblastomas developed in children more than one year and metastatic Ewing tumours. These both diseases are chemosensitive but not curable with conventional chemotherapy. In these indications, high-dose chemotherapy with autologous peripheral blood stem cells transplantation is delivered in patients achieving a good partial remission with conventional treatment. The toxicity of these procedures is high but manageable; these approaches have improved the prognosis of these patients.

  3. 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.

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

    PubMed Central

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

    2016-01-01

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

  5. 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.

  6. 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

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

    PubMed

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

    2016-10-01

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

  8. Poor ovarian reserve.

    PubMed

    Jirge, Padma Rekha

    2016-01-01

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

  9. 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

  10. 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.

  11. 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

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

    PubMed Central

    Rahman, Md. Saydur; Thomas, Peter

    2012-01-01

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

  13. 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

  14. 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

  15. Urban poor program launched.

    PubMed

    1991-01-01

    The government of the Philippines has launched a program to deal with the rapidly growing urban poor population. 60 cities (including Metro Manila) are expected to increase their bloated population by 3.8% over 1990 which would be 27.7 million for 1991. Currently there is an exodus of people from the rural areas and by 2000 half the urban population will be squatters and slum dwellers. Basic services like health and nutrition are not expected to be able to handle this type of volume without a loss in the quality of service. The basic strategy of the new program is to recruit private medical practitioners to fortify the health care delivery and nutrition services. Currently the doctor/urban dweller ration is 1:9000. The program will develop a system to pool the efforts of government and private physicians in servicing the target population. Barangay Escopa has been chosen as the pilot city because it typifies the conditions of a highly populated urban area. The projects has 2 objectives: 1) demonstrate the systematic delivery of health and nutrition services by the private sector through the coordination of the government, 2) reduce mortality and morbidity in the community, especially in the 0-6 age group as well as pregnant women and lactating mothers.

  16. 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

  17. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2015-11-01

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

  1. 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

  2. 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…

  3. 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.

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

    PubMed Central

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

    2015-01-01

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

  5. 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…

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

    SciTech Connect

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

    1991-08-01

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

  7. 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.

  8. 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.

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

    PubMed

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

    2015-09-24

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

  10. 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...

  11. Prenatal synthetic glucocorticoid exposure alters hypothalamic-pituitary-adrenal regulation and pregnancy outcomes in mature female guinea pigs.

    PubMed

    Dunn, Elizabeth; Kapoor, Amita; Leen, Jason; Matthews, Stephen G

    2010-03-01

    Preterm delivery occurs in approximately 10% of all pregnancies. Prenatal exposure to synthetic glucocorticoids (sGCs) reduces the incidence of respiratory distress syndrome (RDS) in these babies. Therefore, administration of multiple courses of sGCs became common practice. Animal and human studies have demonstrated that multiple courses of sGCs can have long-term effects. While the majority of animal studies have been undertaken in male offspring, it is emerging that there are profound sex differences in the consequences of prenatal sGC exposure. To our knowledge, no studies have determined the effects of prenatal sGC exposure on hypothalamic-pituitary-adrenal (HPA) axis function in female offspring while accounting for reproductive cycle status, or determined if there are effects on pregnancy parameters. Pregnant guinea pigs were administered three courses of betamethasone (Beta), dexamethasone (Dex) or vehicle on gestational days 40/41, 50/51 and 60/61. In adulthood (age range: postnatal days 126-165), basal and activated HPA axis function were assessed at various stages of the reproductive cycle. The female offspring were then mated and underwent an undisturbed pregnancy. Females were killed in the luteal phase of the reproductive cycle following litter weaning, and molecular analysis undertaken. In the luteal phase, Beta-exposed females exhibited significantly lower basal salivary cortisol levels (P < 0.05). Dex-exposed females also exhibited significantly lower basal salivary cortisol levels during the luteal phase (P < 0.05), but increased basal salivary cortisol levels during the ostrous phase (P < 0.01). The Beta-exposed females exhibited increased glucocorticoid receptor (GR) mRNA expression in the CA1/2 region of the hippocampus (P < 0.05) and MC2R mRNA in the adrenal cortex (P < 0.05). The Dex-exposed animals exhibited higher hippocampal GR and mineralocorticoid receptor (MR) mRNA levels (P < 0.05). Beta-exposed females showed reduced fecundity (P < 0

  12. 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

  13. Prenatal synthetic glucocorticoid exposure alters hypothalamic–pituitary–adrenal regulation and pregnancy outcomes in mature female guinea pigs

    PubMed Central

    Dunn, Elizabeth; Kapoor, Amita; Leen, Jason; Matthews, Stephen G

    2010-01-01

    Preterm delivery occurs in approximately 10% of all pregnancies. Prenatal exposure to synthetic glucocorticoids (sGCs) reduces the incidence of respiratory distress syndrome (RDS) in these babies. Therefore, administration of multiple courses of sGCs became common practice. Animal and human studies have demonstrated that multiple courses of sGCs can have long-term effects. While the majority of animal studies have been undertaken in male offspring, it is emerging that there are profound sex differences in the consequences of prenatal sGC exposure. To our knowledge, no studies have determined the effects of prenatal sGC exposure on hypothalamic–pituitary–adrenal (HPA) axis function in female offspring while accounting for reproductive cycle status, or determined if there are effects on pregnancy parameters. Pregnant guinea pigs were administered three courses of betamethasone (Beta), dexamethasone (Dex) or vehicle on gestational days 40/41, 50/51 and 60/61. In adulthood (age range: postnatal days 126–165), basal and activated HPA axis function were assessed at various stages of the reproductive cycle. The female offspring were then mated and underwent an undisturbed pregnancy. Females were killed in the luteal phase of the reproductive cycle following litter weaning, and molecular analysis undertaken. In the luteal phase, Beta-exposed females exhibited significantly lower basal salivary cortisol levels (P < 0.05). Dex-exposed females also exhibited significantly lower basal salivary cortisol levels during the luteal phase (P < 0.05), but increased basal salivary cortisol levels during the ostrous phase (P < 0.01). The Beta-exposed females exhibited increased glucocorticoid receptor (GR) mRNA expression in the CA1/2 region of the hippocampus (P < 0.05) and MC2R mRNA in the adrenal cortex (P < 0.05). The Dex-exposed animals exhibited higher hippocampal GR and mineralocorticoid receptor (MR) mRNA levels (P < 0.05). Beta-exposed females showed reduced fecundity (P

  14. Redox and epigenetic regulation of the APE1 gene in the hippocampus of piglets: The effect of early life exposures.

    PubMed

    Langie, Sabine A S; Kowalczyk, Pawel; Tomaszewski, Bartłomiej; Vasilaki, Aphrodite; Maas, Lou M; Moonen, Edwin J; Palagani, Ajay; Godschalk, Roger W L; Tudek, Barbara; van Schooten, Frederik J; Berghe, Wim Vanden; Zabielski, Romuald; Mathers, John C

    2014-06-01

    Oxidative stress via redox reactions can regulate DNA repair pathways. The base excision repair (BER) enzyme apurinic/apyrimidinic endonuclease 1 (APE1) is a key player in the redox regulation of DNA repair. Environmental factors can alter the methylation of DNA repair genes, change their expression and thus modulate BER activity and susceptibility to oxidative DNA damage. Therefore, we hypothesized that epigenetic modifications play a role in the redox regulation of APE1 in hippocampi of newborns and investigated the effect of supplementation of pregnant sows with a diet enriched in antioxidants and other nutrients on oxidative stress, DNA methylation and DNA repair in their offspring. High levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and low levels of glutathione were detected in control piglets after birth compared with supplemented piglets, indicating the presence of oxidative stress. In control animals, this oxidative stress was associated with genomic DNA demethylation, decreased APE1 promoter methylation, increased APE1 expression and with slightly but not statistically significant increased BER-related DNA incision activity. Supplementation of piglets with antioxidants and other nutrients significantly lowered 8-oxodG levels compared to control animals, which was accompanied by overall lower APE1 promoter methylation and enhanced APE1 expression at day 7-28 after birth in supplemented piglets, although DNA incision activity was not significantly different between groups. Preliminary attempts to study the interaction between redox and epigenetic regulatory mechanisms revealed an inverse correlation between APE1 expression and methylation of CpG-sites 11 and 13 in the promoter region, which according to Genomatix "MatInspector" are located in the core binding sites of redox-sensitive transcription factors. We are the first to study methylation of the APE1 promoter and its role in mediating the functional effects of redox reactions induced by

  15. 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

  16. 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

  17. 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…

  18. 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. PMID:26400268

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

    PubMed

    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

  20. 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

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

    PubMed

    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.

  2. Site-specific water quality guidelines: 2. Development of a water quality regulation framework for pulse exposures of mine water discharges at a uranium mine in northern Australia.

    PubMed

    Sinclair, A; Tayler, K; van Dam, R; Hogan, A

    2014-01-01

    The Ranger Uranium Mine, in northern Australia, is monitored by the Supervising Scientist Division (SSD) of the Australian Government to ensure that it does not impact on the highly valued aquatic ecosystems of Kakadu National Park. In 2010, the SSD adopted the continuous monitoring of electrical conductivity (EC) and turbidity, in combination with event-triggered automated grab samples, as its primary water quality monitoring method. The continuous monitoring of EC has shown that mine discharges typically occur over short-term 'pulse' durations of minutes to hours. Given that magnesium (Mg) is the most likely mine-derived solute to approach or exceed the applicable water quality limit value, the focus has been on developing a pulse exposure assessment framework for Mg, as represented by its proxy EC, which is tracked by the continuous monitoring system. This study presents a possible ecotoxicologically derived Mg pulse exposure limit and trigger regulation framework for Magela and Gulungul Creeks and an assessment of historic continuous monitoring EC data from these creeks. This framework demonstrates potential to supersede the current EC guideline and associated trigger levels, which are statistically derived from historic grab sample data.

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

    PubMed Central

    Ratovitski, Edward A.

    2016-01-01

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

  4. 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

  5. Cigarette smoke exposure up-regulates endothelin receptor B in human pulmonary artery endothelial cells: molecular and functional consequences

    PubMed Central

    Milara, J; Ortiz, JL; Juan, G; Guijarro, R; Almudever, P; Martorell, M; Morcillo, EJ; Cortijo, J

    2010-01-01

    BACKGROUND AND PURPOSE Pulmonary arteries from smokers and chronic obstructive pulmonary disease patients show abnormal endothelium-dependent vascular reactivity. We studied the effect of cigarette smoke extract (CSE) on endothelin receptor B (ETB) expression in human pulmonary artery endothelial cells (HPAECs) and its role in endothelial dysfunction. EXPERIMENTAL APPROACH ETB receptor expression was measured by real time RT-PCR, Western blot and immunofluorescence. Cell contraction, intracellular Ca2+, F/G-actin, RhoA activity, myosin light chain phosphorylation, ET, NO, thromboxane (Tx)A2 and reactive oxygen species (ROS) were measured by traction microscopy, fluorescence microscopy, phalloidin fluorescence, colorimetric assay, Western blot, elisa and DCFDA fluorescence respectively. KEY RESULTS Cigarette smoke extract dose-dependently increased ETB receptor expression in HPAECs after 24 h incubation. CSE-induced ETB expression was attenuated by bosentan, the ETB receptor antagonist BQ788, the Rho kinase antagonist Y27632 and the antioxidant N-acetylcysteine. A monoclonal antibody to ET-1 prevented CSE-induced ETB receptor overexpression. Twenty-four hour exposure to ET-1 dose-dependently increased ETB receptor expression, mimicking the effect of CSE. CSE-induced ETB receptor overexpression caused greater cell contraction; increased intracellular Ca2+; increased F/G-actin and RhoA activity; increased myosin light chain phosphorylation; augmented TxA2 and ROS production; and decreased NO after acute ET-1 (10 nM). These effects were attenuated by bosentan, BQ788, Y27632 and N-acetylcysteine. CONCLUSIONS AND IMPLICATION Cigarette smoke extract induced ETB receptor overexpression by a feed forward mechanism mediated partly by ET release, promoting HPAEC dysfunction and attenuated by ETB receptor blockade, Rho kinase and ROS inhibition. These results provide support for the use of bosentan in CS-related endothelial dysfunction. PMID:20698855

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

    PubMed Central

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

    2016-01-01

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

  7. 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

  8. EsMlp, a muscle-LIM protein gene, is up-regulated during cold exposure in the freeze-avoiding larvae of Epiblema scudderiana.

    PubMed

    Bilgen, T; English, T E; McMullen, D C; Storey, K B

    2001-08-01

    Screening of a cDNA library identified transcripts that were up-regulated by cold (4 or -20 degrees C) exposure in larvae of the freeze-avoiding goldenrod gall moth, Epiblema scudderiana. One clone contained a full-length open reading frame encoding a protein of 94 amino acids. The gene product, with 79.1% of residues identical with the Drosophila LIM protein Mlp60A, was named EsMlp and contained a single LIM domain and consensus sequences characteristic of a LIM protein. Transcript levels rose approx twofold when larvae were shifted from 4 to -20 degrees C and approx threefold over the midwinter months compared with larvae sampled in October or April. EsMlp expression was high in larval head (possibly due to expression in pharyngeal muscles) and body wall but was not detected in fat body. Immunoblotting revealed a three- to fourfold increase in EsMlp protein in midwinter larvae (January-February) compared with November-collected animals and a further rise to eightfold higher than November values in larvae collected in April. Cold up-regulation of EsMlp and the pattern of EsMlp levels in the larvae suggest possible roles for the protein, such as in muscle maintenance over the winter or as a preparative function that could facilitate the rapid resumption of development and metamorphosis when environmental temperatures rise in the spring.

  9. 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.

  10. Cystic fibrosis transmembrane conductance regulator in the gills of the climbing perch, Anabas testudineus, is involved in both hypoosmotic regulation during seawater acclimation and active ammonia excretion during ammonia exposure.

    PubMed

    Ip, Yuen K; Wilson, Jonathan M; Loong, Ai M; Chen, Xiu L; Wong, Wai P; Delgado, Inês L S; Lam, Siew H; Chew, Shit F

    2012-08-01

    This study aimed to clone and sequence the cystic fibrosis transmembrane conductance regulator (cftr) from, and to determine the effects of seawater acclimation or exposure to 100 mmol l⁻¹ NH₄Cl in freshwater on its mRNA and protein expressions in, the gills of Anabas testudineus. There were 4,530 bp coding for 1,510 amino acids in the cftr cDNA sequence from A. testudineus. The branchial mRNA expression of cftr in fish kept in freshwater was low (<50 copies of transcript per ng cDNA), but significant increases were observed in fish acclimated to seawater for 1 day (92-fold) or 6 days (219-fold). Branchial Cftr expression was detected in fish acclimated to seawater but not in the freshwater control, indicating that Cl⁻ excretion through the apical Cftr of the branchial epithelium was essential to seawater acclimation. More importantly, fish exposed to ammonia also exhibited a significant increase (12-fold) in branchial mRNA expression of cftr, with Cftr being expressed in a type of Na⁺/K⁺-ATPase-immunoreactive cells that was apparently different from the type involved in seawater acclimation. It is probable that Cl⁻ excretion through Cftr generated a favorable electrical potential across the apical membrane to drive the excretion of NH₄⁺ against a concentration gradient through a yet to be determined transporter, but it led to a slight loss of endogenous Cl⁻. Since ammonia exposure also resulted in significant decreases in blood pH, [HCO₃⁻] and [total CO₂] in A. testudineus, it can be deduced that active NH₄⁺ excretion could also be driven by the exit of HCO₃⁻ through the apical Cftr. Furthermore, A. testudineus uniquely responded to ammonia exposure by increasing the ambient pH and decreasing the branchial bafilomycin-sensitive V-type H⁺-ATPase activity, which suggests that its gills might have low NH₃ permeability.

  11. 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.

  12. The poor man's cell block

    PubMed Central

    Darlington, Ann

    2010-01-01

    The authors describe a simple method for making formalin or isopropyl alcohol vapour fixed cell blocks from fine needle aspiration cytology specimens that we refer to as ‘The Poor Man's Cell Block.’ PMID:20671053

  13. Economic Rationality of the Poor

    ERIC Educational Resources Information Center

    Newton, Jan M.

    1977-01-01

    Utilizing ethnographic data on several rural families, the economic rationality of the rural poor is demonstrated to be implicit in their behavior. Identification is also made of some of the constraints within which these consumer decisions are made. (JC)

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

    PubMed

    Remler, Dahlia K

    2004-02-01

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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  1. 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

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

    PubMed

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

    2014-03-15

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

  3. 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.

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

    PubMed

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

    2014-03-15

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

  5. 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 ...

  6. Adverse effects of metal exposure on chemotaxis towards water-soluble attractants regulated mainly by ASE sensory neuron in nematode Caenorhabditis elegans.

    PubMed

    Xing, Xiaojuan; Du, Min; Zhang, Yanfen; Wang, Dayong

    2009-01-01

    Chemotaxis to water-soluble attractants is mainly controlled by ASE sensory neuron whose specification is regulated by che-1 in Caenorhabditis elegans. Our data suggested that exposure to high concentrations of metals, such as Pb, Cu, Ag, and Cr, would result in severe defects of chemotaxis to water-soluble attractants of NaCl, cAMP, and biotin. Moreover, the morphology of ASE neuron structures as observed by relative fluorescent intensities and relative size of fluorescent puncta of cell bodies, relative lengths of sensory endings in ASE neurons, and the expression patterns of che-1 were obviously altered in metal exposed animals when they meanwhile exhibited obvious chemotaxis defects to water-soluble attractants. In addition, the dendrite morphology could be noticeably changed in animals exposed to 150 micromol/L of Pb, Cu, and Ag. Furthermore, we observed significant decreases of chemotaxis to water-soluble attractants in Pb exposed che-1 mutant at concentrations more than 2.5 micromol/L, and in Cu, Ag, and Cr exposed che-1 mutant at concentrations more than 50 micromol/L. Therefore, impairment of the ASE neuron structures and functions may largely contribute to the appearance of chemotaxis defects to water-soluble attractants in metal exposed nematodes.

  7. 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

  8. Poor Memory: A Case Report.

    ERIC Educational Resources Information Center

    Meltzer, Malcolm L.

    1983-01-01

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

  9. 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

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

    PubMed

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

    2013-10-01

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

  11. 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.

  12. 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.

  13. Genotoxicity of poorly soluble particles.

    PubMed

    Schins, Roel P F; Knaapen, Ad M

    2007-01-01

    Poorly soluble particles such as TiO2, carbon black, and diesel exhaust particles have been evaluated for their genotoxicity using both in vitro and in vivo assays, since inhalation of these compounds by rats at high concentrations has been found to lead to tumor formation. Two principle modes of genotoxic action can be considered for particles, referred to as primary and secondary genotoxicity. Primary genotoxicity is defined as genetic damage elicited by particles in the absence of pulmonary inflammation, whereas secondary genotoxicity implies a pathway of genetic damage resulting from the oxidative DNA attack by reactive oxygen/nitrogen species (ROS/RNS), generated during particle-elicited inflammation. Conceptually, primary genotoxicity might operate via various mechanisms, such as the actions of ROS (e.g., as generated from reactive particle surfaces), or DNA-adduct formation by reactive metabolites of particle-associated organic compounds (e.g., polycyclic aromatic hydrocarbons). Currently available literature data, however, merely indicate that the tumorigenesis of poorly soluble particles involves a mechanism of secondary genotoxicity. However, further research is urgently required, since (1) causality between pulmonary inflammation and genotoxicity has not yet been established, and (2) effects of inflammation on fundamental DNA damage responses that orchestrate mutagenesis and carcinogenic outcome,that is, cell cycle arrest, DNA repair, proliferation, and apoptosis, are currently poorly understood. PMID:17886067

  14. 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.

  15. [Occupational exposure to mycotoxins in various branches of industry].

    PubMed

    Soroka, Piotr M; Cyprowski, Marcin; Szadkowska-Stańczyk, Irena

    2008-01-01

    Mycotoxins are a quite numerous group of substances released as metabolites by molds, which badly affect human and animal health. Their impact on organisms resulting from alimentary exposure is well recognized, but the mechanisms by which they exert their health effects after inhalation exposure are still poorly investigated. The aim of this work was to review the literature concerning the outcomes of occupational exposure to mycotoxins present in the work environment. The author discusses the major mycotoxin classes, their chemical structure, some physicochemical properties and biological activity properties. This paper summarizes the results of investigations on the impact of occupational exposure to molds present in the workplace air in various branches of industry. Problems of identifying the mechanism of health effects exerted due inhalation exposure to mycotoxins are also discussed. This review shows that there is lack of good hygiene standards and legislation regulating the presence of these compounds in the workplace air. These is due to insufficient number of analyses aimed at estimating short-term inhalation exposure to mycotoxins and lack of monitoring of long-term exposure and its health effects. The authors concludes that occupational exposure to mycotoxins and their role in the development of pathological changes in the respiratory system require further investigations. PMID:19143225

  16. Why are the many poor?

    PubMed

    Townsend, P

    1986-01-01

    In this article the author restates the same arguments put forward in the first Fabian Tract of 1884 entitled Why Are the Many Poor? Today, mass poverty is still the central problem facing the British nation and all nations. The only long-term remedy is to restrict the power and wealth of the rich, to dismantle the present structures of social privilege, and to build social institutions based on fair allocation of wealth and on social equality. The public debate of one hundred years ago on the connections between poverty and wealth is revived in this article.

  17. Long-term arsenic exposure induces histone H3 Lys9 dimethylation without altering DNA methylation in the promoter region of p16(INK4a) and down-regulates its expression in the liver of mice.

    PubMed

    Suzuki, Takehiro; Nohara, Keiko

    2013-09-01

    Long-term exposure of humans to high concentrations of arsenic is associated with an increased risk of cancer. Previous studies have suggested that arsenic exposure promotes tumorigenesis by inducing changes in the expression of tumor-related genes by dysregulating DNA methylation at tumor-related gene loci. However, the causal relationships between epigenetic changes and both arsenic exposure and tumorigenesis are still unclear. In the present study, we investigated whether arsenic can change the expression of tumor-related genes by inducing epigenetic modifications before tumorigenesis. We did so by investigating the effects of long-term arsenic exposure on representative epigenetic modifications, DNA methylation and histone modifications, in the tumor-free normal liver of C57Bl/6 mice. We focused on the tumor-related genes, p16(INK4a) , RASSF1A, Ha-ras and ER-α as target genes, because their expression and promoter methylation status in mice have been reported to be affected by long-term arsenic exposure. The results showed that long-term arsenic exposure induced a significant decrease in expression of p16(INK4a) associated with an increase in level of dimethylated histone H3 lysine 9 (H3K9), a transcription-suppressive histone modification, in the promoter region, but that DNA methylation of the promoter region was unaffected. The results also showed a significant increase in recruitment of H3K9 histone methyltransferase G9a to the promoter after arsenic exposure. These findings suggest that long-term arsenic exposure may induce down-regulation of p16(INK4a) by targeting recruitment of G9a and H3K9 dimethylation without altering DNA methylation before tumorigenesis in the liver.

  18. Seven poor clusters of galaxies

    NASA Astrophysics Data System (ADS)

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

    1984-08-01

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

  19. Exposure assessment of trichloroethylene.

    PubMed

    Wu, C; Schaum, J

    2000-05-01

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

  20. Exposure assessment of trichloroethylene.

    PubMed Central

    Wu, C; Schaum, J

    2000-01-01

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

  1. 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.

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

    PubMed

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

    2016-01-01

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

  3. 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.

  4. 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.

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

    PubMed Central

    Grubliauskiene, Aiste; Dewitte, Siegfried

    2014-01-01

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

  6. A history of corticosterone exposure regulates fear extinction and cortical NR2B, GluR2/3, and BDNF.

    PubMed

    Gourley, Shannon L; Kedves, Alexia T; Olausson, Peter; Taylor, Jane R

    2009-02-01

    A history of exposure to stressors may be a predisposing factor for developing posttraumatic stress disorder (PTSD) after trauma. Extinction of conditioned fear appears to be impaired in PTSD, but the consequences of prior stress or excess glucocorticoid exposure for extinction learning are not known. We report that prior chronic exposure to the stress hormone, corticosterone (CORT), decreases endogenous CORT secretion upon context reexposure and impairs extinction after contextual fear conditioning in rats, while leaving fear memory acquisition and expression intact. Posttraining administration of the glucocorticoid receptor (GR) antagonist, RU38486, partially mimicked prior CORT exposure effects on freezing during fear extinction training. Extinction of conditioned fear is an active learning process thought to involve glutamatergic targets--including specific NMDA and AMPA receptor subunits--in the ventromedial prefrontal cortex (vmPFC), which includes the prelimbic, infralimbic, and medial orbitofrontal cortices. After CORT exposure, decreases in the NMDA receptor NR2B subunit and AMPA receptor subunits, GluR2/3, as well as brain-derived neurotrophic factor, were detected in cortical regions, but not dorsal hippocampus (CA1). Receptor subunit expression levels in the vmPFC correlated with freezing during training. In addition, prior CORT selectively decreased sucrose preference, consistent with established models of anhedonia and with blunted affect in PTSD. Together, these data suggest a cellular mechanism by which chronically elevated glucocorticoid exposure--as may be experienced during repeated exposure to stressors--interferes with the neural systems that modulate behavioral flexibility and may thereby contribute to psychopathological fear states.

  7. Regulation at multiple levels control the expression of folate transporters in liver cells in conditions of ethanol exposure and folate deficiency.

    PubMed

    Thakur, Shilpa; Kaur, Jyotdeep

    2015-01-01

    Complex regulatory mechanisms control the expression of folate transporters within cells. Liver is the primary reserve of the folate stores within the body. As excessive alcohol consumption or inefficient dietary folate intake are known to create folate deficiency, so therefore the current study was designed to explore various regulatory mechanisms controlling the expression of folate transport in liver cells in conditions of ethanol exposure and folate deficiency. In order to see whether the effects mediated by the treatments are reversible or not, ethanol removal, and folate repletion was done after ethanol exposure and folate deficiency treatment respectively. Folate deficiency resulted an increase, whereas ethanol treatment decreased the folic acid uptake within the cells. The alterations in folic acid uptake were in agreement with the observed changes in the expression of folate transporters. Ethanol exposure resulted an increase in promoter methylation of reduced folate carrier; however, folate deficiency had no effect. The effects produced by ethanol exposure and folate deficiency were found to be reversible in nature as depicted in case of ethanol removal and folate repletion group. Rate of synthesis of folate transporters was found to be increased whereas half lives of mRNA of folate transporters was found to be decreased on folate deficiency treatment and reverse was the case on ethanol treatment. Overall, alteration in the expression of folate transporters under ethanol exposure and folate deficient conditions can be attributed to those regulatory mechanisms which work at the mRNA level.

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

    PubMed Central

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

    2015-01-01

    Leukemias and hematopoietic disorders induced by benzene may arise from the toxicity of benzene to hematopoietic stem or progenitor cells (HS/PCs). Since there is a latency period between initial benzene exposure and the development of leukemia, subsequent impact of benzene on HS/PCs are crucial for a deeper understanding of the carcinogenicity and hematotoxicity in post-exposure stage. This study aims to explore the effects of benzene on HS/PCs and gene-expression in Wnt, Notch and Hh signaling pathways in post-exposure stage. The C3H/He mice were injected subcutaneously with benzene (0, 150, 300 mg/kg/day) for three months and were monitored for another 10 months post-exposure. The body weights were monitored, the relative organ weights, blood parameters and bone marrow smears were examined. Frequency of lineage- sca-1+ c-kit+ (LSK) cells, capability of colony forming and expression of genes in Wnt, Notch and Hedghog (Hh) signaling pathways were also analyzed. The colony formation of the progenitor cells for BFU-E, CFU-GEMM and CFU-GM was significantly decreased with increasing benzene exposure relative to controls, while no significant difference was observed in colonies for CFU-G and CFU-M. The mRNA level of cyclin D1 was increased and Notch1 and p53 were decreased in LSK cells in mice exposed to benzene but with no statistical significance. These results suggest that subsequent toxic effects of benzene on LSK cells and gene expression in Wnt, Notch and Hh signaling pathways persist in post-exposure stage and may play roles in benzene-induced hematotoxicity. PMID:26262635

  9. 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.

  10. Epigenetic regulation in obesity.

    PubMed

    Lavebratt, C; Almgren, M; Ekström, T J

    2012-06-01

    The availability to the DNA strand and the activity of the transcription machinery is crucial for the cell to use the information in the DNA. The epigenetic mechanisms DNA methylation, modification of histone tails, other chromatin-modifying processes and interference by small RNAs regulate the cell-type-specific DNA expression. Epigenetic marks can be more or less plastic perpetuating responses to various molecular signals and environmental stimuli, but in addition apparently stochastic epigenetic marks have been found. There is substantial evidence from animal and man demonstrating that both transient and more long-term epigenetic mechanisms have a role in the regulation of the molecular events governing adipogenesis and glucose homeostasis. Intrauterine exposure such as poor maternal nutrition has consistently been demonstrated to contribute to a particular epigenotype and thereby developmental metabolic priming of the exposed offspring in animal and man. Epigenetic modifications can be passed not only from one cell generation to the next, but metabolic disease-related epigenotypes have been proposed to also be transmitted germ-line. Future more comprehensive knowledge on epigenetic regulation will complement genome sequence data for the understanding of the complex etiology of obesity and related disorder.

  11. Body temperature regulation in diabetes.

    PubMed

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

    2016-01-01

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

  12. 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

  13. Body temperature regulation in diabetes.

    PubMed

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

    2016-01-01

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

  14. Confinement exposure induces glucose regulated protein 75 (GRP75/mortalin/mtHsp70/PBP74/HSPA9B) in the hepatic tissue of gilthead sea bream (Sparus aurata L.).

    PubMed

    Bermejo-Nogales, Azucena; Benedito-Palos, Laura; Saera-Vila, Alfonso; Calduch-Giner, Josep Alvar; Sitjà-Bobadilla, Ariadna; Pérez-Sánchez, Jaume

    2008-03-01

    Glucose regulated protein 75 (GRP75/mortalin/mtHsp70/PBP74/HSPA9B) is a molecular chaperone that was partially cloned and sequenced in gilthead sea bream (Sparus aurata L.) using a RT-PCR and 3'RACE approach. The deduced amino acid sequence supported the early vertebrate divergence of the heat shock protein 70 family into cytoplasmic Hsp70/Hsc70 group, endoplasmic reticulum-resident group and the mitochondrial-type group of GRP75. The tissue-specific regulation of GRP75 was analyzed by real-time PCR and Western blot after acute (24 h, 120 kg/m(3)) and prolonged confinement exposure (3 weeks-trial, 45-50 kg/m(3)). In both experiments, GRP75 gene expression was not significantly altered in brain, head kidney and gills. By contrast, hepatic transcripts of GRP75 were up-regulated and the magnitude of the response was dependent on the intensity of stressor. Furthermore, similar increments in hepatic transcripts and protein levels of GRP75 were found after prolonged confinement exposure. In addition, these stressed animals exhibited a 10% reduction in feed efficiency, significantly increased glycaemia and plasma peroxidases, and their plasma transaminases and respiratory burst of circulating leucocytes were significantly decreased. This stress-mediated response may act in concert with the increased production of hepatic GRP75 to protect metabolically active tissues against oxidative damage.

  15. 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…

  16. 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.

  17. 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...

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

    PubMed

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

    2015-11-01

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

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

    PubMed

    Kim, Namsuk

    2012-04-01

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

  20. Occupational solvent exposure and cognition

    PubMed Central

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

    2012-01-01

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

  1. Military Exposures

    MedlinePlus

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

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

    PubMed

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

    2016-01-01

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

  3. 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

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

    PubMed

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

    2016-01-25

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

  5. 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.

  6. Involvement of extracellular signal-regulated kinase (ERK1/2)-p53-p21 axis in mediating neural stem/progenitor cell cycle arrest in co-morbid HIV-drug abuse exposure.

    PubMed

    Malik, Shaily; Saha, Rinki; Seth, Pankaj

    2014-06-01

    Neurological complications in opioid abusing Human Immunodeficiency Virus-1 (HIV-1) patients suggest enhanced neurodegeneration as compared to non-drug abusing HIV-1 infected population. Neural precursor cells (NPCs), the multipotent cells of the mammalian brain, are susceptible to HIV-1 infection and as opiates also perturb their growth kinetics, detailed mechanistic studies for their co-morbid exposure are highly warranted. Using a well characterized in vitro model of human fetal brain-derived neural precursor cells, we investigated alterations in NPC properties at both acute and chronic durations. Chronic morphine and Tat treatment attenuated proliferation in NPCs, with cells stalled at G1-phase of the cell cycle. Furthermore HIV-Tat and morphine exposure increased activation of extracellular signal-regulated kinase-1/2 (ERK1/2), enhanced levels of p53 and p21, and decreased cyclin D1 and Akt levels in NPCs. Regulated by ERK1/2 and p53, p21 was found to be indispensible for Tat and morphine mediated cell cycle arrest. Our study elaborates on the cellular and molecular machinery in NPCs and provides significant mechanistic details into HIV-drug abuse co-morbidity that may have far reaching clinical consequences both in pediatric as well as adult neuroAIDS.

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

    PubMed

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

    2016-06-01

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

  8. Ascorbic acid regulation in stress responses during acute cold exposure and following recovery in juvenile Chinese soft-shelled turtle (Pelodiscus sinensis).

    PubMed

    Chen, Bo-jian; Niu, Cui-juan; Yuan, Lin

    2015-06-01

    Intense temperature change often leads to increased oxidative stress in many animals with a few exceptions, including the turtle. To date, little is known about the mechanism of protective antioxidative defenses in turtles during acute temperature change, specifically the role that the antioxidant ascorbic acid (AA) plays. In this study, Chinese soft-shelled turtles (Pelodiscus sinensis) were initially acclimated at 28°C (3 wks), exposed to acute cold condition (8°C, 8 h) and finally placed in recovery (28°C, 24 h). L-Gulonolactone oxidase (GLO) mRNA exhibited a stable transcription pattern during the intense thermal fluctuation. GLO activity also remained stable, which validated the mRNA expression pattern. The similar Q10 values for GLO activity in the different treatment groups at incubation temperatures of 28°C and 8°C indicated that the GLO activity response to thermal change exhibited a temperature-dependent enzymatic kinetic characteristic. The AA storage was tissue-specific as well as the AA re-supply in the recovery period, with brain as the priority. Despite the insufficient transport during cold exposure, the plasma AA reservoir greatly contributed to the redistribution of AA during recovery. Depending on the prominent GLO activity, the high level of tissue-specific AA storage and the extraordinary plasma AA transport potential, the Chinese soft-shelled turtle endured severe thermal fluctuations with no apparent oxidative stress. However, the significant decrease in AA concentration in the brain tissue during acute cold exposure suggested that such a strategy may not be sufficient for prolonged cold exposure.

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

    PubMed

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

    2014-05-15

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

  10. Alternations in neuroendocrine and endocrine regulation of reproduction in male goldfish (Carassius auratus) following an acute and chronic exposure to vinclozolin, in vivo.

    PubMed

    Golshan, Mahdi; Hatef, Azadeh; Zare, Ava; Socha, Magdalena; Milla, Sylvain; Gosiewski, Grzegorz; Fontaine, Pascal; Sokołowska-Mikołajczyk, Mirosława; Habibi, Hamid R; Alavi, Sayyed Mohammad Hadi

    2014-10-01

    The fungicide vinclozolin (VZ) is in use globally and known to disrupt reproductive function in male. The present study tested the hypothesis that VZ disrupts testicular function in goldfish (Carassius auratus) by affecting brain-pituitary-testis axis. Goldfish were exposed to 100, 400 and 800 μg/L VZ and 5 μg/L 17β-estradiol (E2) for comparison. In VZ treated goldfish, 11-ketotesteosterone (11-KT) secretion was changed depending on dose and duration period of treatment. Following 7 days of exposure, 11-KT was decreased in goldfish exposed to 800 μg/L VZ, while it was increased in goldfish exposed to 100 μg/L VZ after 30 days of exposure. Circulating E2 level was unchanged in VZ treated goldfish, however the E2/11-KT ratio was increased in a concentration-related manner. In E2 treated goldfish, circulatory 11-KT and E2 levels were decreased and increased, respectively, which resulted in an increase in the E2/11-KT ratio. Exposure to VZ at 100 μg/L caused a significant increase in the circulatory luteinizing hormone (LH) after 30 days. In E2 treated fish circulatory LH was decreased, significantly. Transcripts of genes encoding gonadotropin-releasing hormone and androgen receptor in the brain, and those of genes encoding LH and follicle-stimulating hormone receptors, StAR, CYP17, and 3β-HSD in the testis changed in VZ-treated goldfish depending on concentration and period of treatment. mRNA of genes encoding vitellogenin and estrogen receptor in the liver and cytochrome P450 aromatase in the brain were increased in E2-treated goldfish. The results suggest that VZ-induced changes in 11-KT were due to disruption in brain-pituitary-testis axis and provide integrated characterization of VZ-related reproductive disorders in male fish.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-08-01

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

  13. 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...

  14. 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…

  15. 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…

  16. Extent of Malnourishment among the Rural Poor.

    ERIC Educational Resources Information Center

    Shotland, Jeffrey

    1989-01-01

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

  17. 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…

  18. Cognitive and Behavioral Distancing from the Poor.

    ERIC Educational Resources Information Center

    Lott, Bernice

    2002-01-01

    Suggests that distancing is the dominant response to poor people by those who are not poor and that distancing, separation, exclusion, and devaluing operationally define discrimination. Examines U.S. classism in the context of theoretical propositions about the moral exclusion of stigmatized others. Describes cognitive, institutional, and…

  19. 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

  20. The effect of acute dichlorodiphenyltrichloroethane exposure on hypermethylation status and down-regulation of p53 and p16INK4a genes in rat liver.

    PubMed

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

    2016-05-01

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

  1. Prenatal Ethanol Exposure Up-Regulates the Cholesterol Transporters ATP-Binding Cassette A1 and G1 and Reduces Cholesterol Levels in the Developing Rat Brain

    PubMed Central

    Zhou, Chunyan; Chen, Jing; Zhang, Xiaolu; Costa, Lucio G.; Guizzetti, Marina

    2014-01-01

    Aims: Cholesterol plays a pivotal role in many aspects of brain development; reduced cholesterol levels during brain development, as a consequence of genetic defects in cholesterol biosynthesis, leads to severe brain damage, including microcephaly and mental retardation, both of which are also hallmarks of the fetal alcohol syndrome. We had previously shown that ethanol up-regulates the levels of two cholesterol transporters, ABCA1 (ATP binding cassette-A1) and ABCG1, leading to increased cholesterol efflux and decreased cholesterol content in astrocytes in vitro. In the present study we investigated whether similar effects could be seen in vivo. Methods: Pregnant Sprague-Dawley rats were fed liquid diets containing 36% of the calories from ethanol from gestational day (GD) 6 to GD 21. A pair-fed control groups and an ad libitum control group were included in the study. ABCA1 and ABCG1 protein expression and cholesterol and phospholipid levels were measured in the neocortex of female and male fetuses at GD 21. Results: Body weights were decreased in female fetuses as a consequence of ethanol treatments. ABCA1 and ABCG1 protein levels were increased, and cholesterol levels were decreased, in the neocortex of ethanol-exposed female, but not male, fetuses. Levels of phospholipids were unchanged. Control female fetuses fed ad libitum displayed an up-regulation of ABCA1 and a decrease in cholesterol content compared with pair-fed controls, suggesting that a compensatory up-regulation of cholesterol levels may occur during food restriction. Conclusion: Maternal ethanol consumption may affect fetal brain development by increasing cholesterol transporters’ expression and reducing brain cholesterol levels. PMID:25081040

  2. Exposure of LS-180 Cells to Drugs of Diverse Physicochemical and Therapeutic Properties Up-regulates P-glycoprotein Expression and Activity

    PubMed Central

    Abuznait, Alaa H.; Patrick, Shawn G.; Kaddoumi, Amal

    2011-01-01

    Purpose Drug transporters are increasingly recognized as important determinants of variability in drug disposition and therapeutic response, both in pre-clinical and clinical stages of drug development process. The role P-glycoprotein (P-gp) plays in drug interactions via its inhibition is well established. However, much less knowledge is available about drugs effect on P-gp up-regulation. The objective of this work was to in vitro investigate and rank commonly used drugs according to their potencies to up-regulate P-gp activity utilizing the same experimental conditions. Methods The in vitro potencies of several drugs of diverse physicochemical and therapeutic properties including rifampicin, dexamethasone, caffeine, verapamil, pentylenetetrazole, hyperforin, and β-estradiol over broad concentration range to up-regulate P-gp expression and activity were examined. For dose-response studies, LS-180 cells were treated with different concentrations of the selected drugs followed by P-gp protein and gene expressions analyses. P-gp functionality was determined by uptake studies with rhodamine 123 as a P-gp substrate, followed by Emax/EC50 evaluation. Results The results demonstrated a dose-dependent increase in P-gp expression and activity following treatments. At 50 μM concentration (hyperforin, 0.1 μM), examined drugs increased P-gp protein and gene expressions by up to 5.5 and 6.2-fold, respectively, while enhanced P-gp activity by 1.8–4-fold. The rank order of these drugs potencies to up-regulate P-gp activity was as following: hyperforin ⋙ dexamethasone ≈ β-estradiol > caffeine > rifampicin ≈ pentylenetetrazole > verapamil. Conclusions These drugs have the potential to be involved in drug interactions when administered with other drugs that are P-gp substrates. Further studies are needed to in vivo evaluate these drugs and verify the consequences of such induction on P-gp activity for in vitro-in vivo correlation purposes. PMID:21733412

  3. 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.

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

    PubMed

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

    2015-08-15

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

  5. Tackling poor parenting: a public health issue.

    PubMed

    Poole, Judith

    2003-01-01

    The adverse consequences associated with poor parenting persist down the generations and are a problem for society as well as individuals. The author cites evidence suggesting that in many cases poor parenting is associated with socioeconomic deprivation, including health inequalities. She argues that most parents (especially mothers, as the main child carers) are motivated to do their best for their children but that many families struggle against poverty. Poor parenting skills may be a product of poverty and social exclusion rather than the fault of individual parents. A public health approach, based on partnership with parents to meet their expressed needs in appropriate ways, could offer a constructive way forward.

  6. 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)

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

    PubMed

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

    2014-01-01

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

  8. 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.

  9. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  12. 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.

  13. How School Taught Me I Was Poor

    ERIC Educational Resources Information Center

    Sapp, Jeff

    2009-01-01

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

  14. Why so many children are poor.

    PubMed

    Betson, D M; Michael, R T

    1997-01-01

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

  15. 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…

  16. Environmental and Occupational Exposures in Immigrant Health

    PubMed Central

    Eamranond, Pracha P.; Hu, Howard

    2008-01-01

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

  17. Photometric Properties of Galaxies in Poor Clusters

    NASA Astrophysics Data System (ADS)

    Sharma, M.; Prabhu, T.

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

  18. 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.

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

    PubMed Central

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

    2015-01-01

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

  20. 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

    2015-10-01

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

  1. Perinatal exposure to vitamin A differentially regulates chondrocyte growth and the expression of aggrecan and matrix metalloprotein genes in the femur of neonatal rats.

    PubMed

    Zhang, Yao; Wray, Amanda E; Ross, A Catharine

    2012-04-01

    Vitamin A (VA) and its active form, retinoic acid (RA), are regulators of skeletal development. In the present study, we investigated if maternal VA intake during pregnancy and lactation, as well as direct oral supplementation of neonates with VA + RA (VARA) in early life, alters neonatal bone formation and chondrocyte gene expression. Offspring of dams fed 3 levels of VA (marginal, adequate, and supplemented) for 10 wk were studied at birth (P0) and postnatal day 7 (P7). One-half of the newborns received an oral supplement of VARA on P1, P4, and P7. Tissues were collected on P0 and 6 h after the last dose on P7. Pup plasma and liver retinol concentrations were increased by both maternal VA intake and VARA (P < 0.01). Although maternal VA did not affect bone mineralization as assessed by von Kossa staining, newborn femur length was increased with maternal VA (P < 0.05). VARA supplementation of neonates increased the length of the hypertrophic zone only in VA-marginal pups, close to that in neonates from VA-adequate dams, suggesting VARA caused a catching up of growth that was limited by low maternal VA intake. Maternal diet did not alter type X nor type II collagen mRNA. However, VARA-treated pups from VA-supplemented dams had reduced mRNA for aggrecan, a major component of cartilage matrix, and increased mRNA for matrix metalloproteinase (MMP)13, which catalyzes the degradation of aggrecan and collagens. These results suggest that moderately high maternal VA intake combined with neonatal VARA supplementation can reduce the ratio of aggrecan:MMP, which may unfavorably alter early bone development.

  2. 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.

  3. Mechanism of Ultrasonic Introduction of Particles into a Poorly Wetting Liquid

    NASA Astrophysics Data System (ADS)

    Kudryashova, O. B.; Kozyrev, A. V.; Vorozhtsov, S. A.

    2016-09-01

    The process of introduction of submicron agglomerates and nanostructured particles into a poorly wetting liquid exposed to ultrasound is theoretically considered. The main dependences relating the exposure time to the physical and chemical properties of particles and liquid as well as to the characteristics of acoustic radiation are obtained.

  4. 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…

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

    PubMed

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

    2014-12-01

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

  6. Residential Mobility among the Rural Poor.

    ERIC Educational Resources Information Center

    Fitchen, Janet M.

    1994-01-01

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

  7. Photometric Properties of Poor Cluster Galaxies

    NASA Astrophysics Data System (ADS)

    Sharma, M.; Prabhu, T. P.

    2002-12-01

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

  8. University Students with Poor Reading Comprehension

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  9. 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…

  10. The Communication Environment of the Urban Poor.

    ERIC Educational Resources Information Center

    Dervin, Brenda; Greenberg, Bradley, S.

    The purpose of this document is to review the growing body of literature focusing on poverty and communication, assess it, and posit directions for future work. In all, some 4000 different studies are examined to develop an overview of the communication environment of the urban poor. No more than 200 had some relevance to poverty-communication;…

  11. Getting to Know L2 Poor Comprehenders

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  12. 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…

  13. 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…

  14. 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…

  15. Poor, Rural Neighborhoods and Early School Achievement.

    ERIC Educational Resources Information Center

    Bickel, Robert; Smith, Cynthia; Eagle, Teresa Hardman

    A study sought to identify the existence of neighborhood effects on school achievement that are independent of social class and family background among students from poor, rural neighborhoods. Ethnographic material yielded a concept of rural West Virginia neighborhoods in which residents expect their encounters to be friendly, informal, almost…

  16. Adult Literacy and the Poor Farming People.

    ERIC Educational Resources Information Center

    Mathur, J. C.

    1978-01-01

    In discussing Rafe-uz-Zaman's essay on adult literacy and national development (see v9, n1 of this journal), the author cites examples to support his thesis that mass literacy campaigns in predominately agricultural countries can be successful only if there is simultaneous undertaking of economic development programs focused on the rural poor. (MF)

  17. 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…

  18. Promoting Upward Mobility for the Working Poor.

    ERIC Educational Resources Information Center

    Rupured, Michael

    2000-01-01

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

  19. 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…

  20. Health and economic expansion in poor lands.

    PubMed

    Malenbaum, W

    1973-01-01

    Economic progress in poor lands remains a major goal as current efforts continue to yield limited advance for the nations where most of the world's people continue to live in poverty. The income gap between poor lands and the rich world continue to grow. Effective solutions require new approaches in three areas of science: the process of economic development, the dynamics of population growth, and the function of the health of man. Neither history or theory provides economic progress a basis for policy or programs in any of these areas. The motivation and attitudes of man are essential elements in the process of population and production change, an emphasis which contrasts with the more conventional concern with a nation's material and physical resources in the process of economic and demographic advance. Health programs thus offer a major contribution to the process of economic and population development. Improved health in poor areas is a joint product of inputs from other professions as much as from the medical and public health sciences proper. In fact, improved health in developing lands may itself derive for the most part from expanding production relative to population. The basic contribution of the health sciences in poor lands is the involvement of health interventions with attitude changes essential to economic progress and to the rates of growth of production and population. Analysis of the interdependence of health, demographic and economic progress is suggested for India, Appalachia and South Africa and reported for Ethiopia, guatemala and St. Lucia.

  1. 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…

  2. 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…

  3. The environments of poor clusters of galaxies

    NASA Astrophysics Data System (ADS)

    Bliton, Mark Alan

    Poor clusters of galaxies are fundamental cosmological structures, but have received relatively little attention compared to rich, Abell clusters. In order to fully understand galaxy clustering, we must examine galaxy associations of all masses and richness levels. We have therefore undertaken an X-ray, optical, and radio investigation of the environments of poor clusters, in order to understand how their galaxies, radio sources, and intracluster media influence and interact with one another. To examine the global properties of poor clusters as observed in these three wavelength regimes, we have utilized three major sky surveys: the ROSAT All-Sky Survey, the Digitized Sky Survey, and the NRAO VLA Sky Survey. For the purposes of this study, we construct a complete, volume-limited sample of 306 poor clusters in the redshift range 0.01--0.03. We compute the X-ray luminosity function (XLF) of poor clusters and compare to XLFs of nearby, rich, Abell clusters. We also compute the bivariate radio luminosity function (BRLF), which is the fraction of radio-loud galaxies of a given optical magnitude. Higher richness clusters produce increased AGN activity in M* galaxies. We find that only clusters with an elliptical as their dominant galaxy possess an ICM. This implies that the presence of a dominant elliptical at the center of a poor cluster is more closely linked to the presence of an ICM than the overall morphological mix of the cluster galaxies. We also find a strong anti-correlation between richness and the fraction of starburst radio galaxies in poor clusters. There may be two factors which contribute to this anti-correlation. For richer clusters, the ICM density may be sufficiently strong that it can strip gas from starforming galaxies, thereby reducing the level of star formation in richer systems. Conversely, the poorest clusters contain higher galaxy compactness, which results in smaller nearest-neighbor distances between galaxies. These smaller galaxy separations

  4. 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.

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

    PubMed Central

    2012-01-01

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

  6. 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....

  7. 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....

  8. 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 ...

  9. Hypotonic exposures.

    PubMed

    Flynn, W J; Hill, R M

    1984-03-01

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

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

    PubMed

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

    2013-07-01

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

  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. 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.

  13. 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.

  14. Medical risk: implicating poor pregnant women.

    PubMed

    Handwerker, L

    1994-03-01

    Since 1987 the United States courts have increasingly relied on medical testimony to prosecute women labeled 'high risk' for failure to comply with medical advice when their fetuses or babies die. Drawing on fieldwork in a public prenatal clinic in Northern California, it is argued that risk does not represent scientific certainty. While the assessment and management of risk is not standardized or consistently applied in the clinic, health care providers and the legal system make decisions as if risk is unambiguous 'fact'. Consequently, labeling poor pregnant women 'high risk', implicitly and explicitly makes them accountable if they are unable to change their behavior as prescribed by health professionals. Through an examination of the dilemmas facing poor pregnant women seeking prenatal care, this paper suggests how attempts to prosecute women may discourage rather than encourage them to seek care. Overall, there is a need for understanding the complexities of risk and its usages in medical and legal settings.

  15. [Poor school performance: an updated review].

    PubMed

    Siqueira, Cláudia Machado; Gurgel-Giannetti, Juliana

    2011-01-01

    This study aims to develop a comprehensive review on the issue of poor school performance for professionals in both health and education areas. It discusses current aspects of education, learning and the main conditions involved in underachievement. It also presents updated data on key aspects of neurobiology, epidemiology, etiology, clinical presentation, comorbidities and diagnosis, early intervention and treatment of the major pathologies comprised. It is a comprehensive, non-systematic literature review on learning, school performance, learning disorders (dyslexia, dyscalculia and dysgraphia), attention deficit / hyperactivity disorder (ADHD) and developmental coordination disorder (DCD). Poor school performance is a frequent problem faced by our children, causing serious emotional, social and economic issues. An updated view of the subject facilitates clinical reasoning, accurate diagnosis and appropriate treatment. PMID:21390464

  16. Poor response to treatment: beyond medication

    PubMed Central

    Carvajal, César

    2004-01-01

    In psychiatry, one of the main factors contributing to poor response to pharmacological treatment is adherence. Noncompliance with maintenance treatments for chronic illnesses such as schizophrenia and affective disorders can exceed 50%, Poor adherence can be due to drug-related factors (tolerance, complexity of prescription, side effects, or cost), patient-related variables (illness symptoms, comorbidity, insight capacity, belief system, or sociocultural environment), and physician-related factors (communication or psychoeducational style). Psychosocial treatments must be used in conjunction with medication during the maintenance phase to improve adherence to treatment and to achieve - through the management of psychological variables - better social, work, and family functioning. This article reviews the concepts of adherence and noncompliance, and their impact on maintenance treatments, as well as the effect of dealing with psychosocial factors in psychiatric treatment. PMID:22034452

  17. 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.

  18. 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

  19. 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...

  20. 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...

  1. 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...

  2. 30 CFR 62.130 - Permissible exposure level.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  3. 30 CFR 62.130 - Permissible exposure level.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Permissible exposure level. 62.130 Section 62... REGULATIONS OCCUPATIONAL NOISE EXPOSURE § 62.130 Permissible exposure level. (a) The mine operator must assure that no miner is exposed during any work shift to noise that exceeds the permissible exposure level....

  4. 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

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

    PubMed

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

    2011-07-01

    Prenatal exposures to neurotoxins and postnatal parenting practices have been shown to independently predict variations in the cognitive development and emotional-behavioral well-being of infants and children. We examined the independent contributions of prenatal cigarette exposure and infant learning stimulation, as well as their inter-relationships in predicting variations in the proficiency of executive attention, a core element of cognitive control and self-regulation. Participants were an ethnic-racially, socio-economically diverse sample of 249 children followed from birth in the Project on Human Development in Chicago Neighborhoods. We obtained histories of prenatal exposure to alcohol, cigarettes, and other drugs, and we assessed socio-economic status and learning stimulation during a home visit when the participants were infants. In childhood we utilized the Attention Networks Test to assess the proficiency of executive attention during two home visits, one year apart. Accounting for age, SES, prenatal alcohol exposure, and baseline performance, we found that prenatal cigarette exposure impaired the speed of executive attention. Infant learning stimulation mitigated these effects, and predicted better accuracy of executive attention as well, suggestive of both protective and health promoting effects. Effect sizes for these relations, whether examined independently or by their inter-relationships, were comparable to if not greater in magnitude than the effects of age on speed and accuracy, highlighting the importance of these very early experiences in shaping the proficiency of self-regulation. Since executive attention is central to cognitive control and self-regulation, previously described relations between prenatal cigarette exposure, parenting practices, and some forms of childhood psychopathology may be contingent on how early learning stimulation contributes to the proficiency of executive attention through direct and indirect effects. Furthermore

  6. 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

  7. Poor mental health status and aggression are associated with poor driving behavior among male traffic offenders

    PubMed Central

    Abdoli, Nasrin; Farnia, Vahid; Delavar, Ali; Esmaeili, Alirez; Dortaj, Fariborz; Farrokhi, Noorali; Karami, Majid; Shakeri, Jalal; Holsboer-Trachsler, Edith; Brand, Serge

    2015-01-01

    Background In Iran, traffic accidents and deaths from traffic accidents are among the highest in the world, and generally driver behavior rather than either technical failures or environmental conditions are responsible for traffic accidents. In the present study, we explored the extent to which aggressive traits, health status, and sociodemographic variables explain driving behavior among Iranian male traffic offenders. Method A total of 443 male driving offenders (mean age: M =31.40 years, standard deviation =9.56) from Kermanshah (Iran) took part in the study. Participants completed a questionnaire booklet covering sociodemographic variables, traits of aggression, health status, and driving behavior. Results Poor health status, such as symptoms of depression, anxiety, insomnia, and social dysfunction, and also higher levels of trait aggression explained poor driving behavior. Multiple regressions indicated that poor health status, but not aggression, independently predicted poor driving behavior. Conclusion Results suggest that health status concerns are associated with poor driving behavior. Prevention and intervention might therefore focus on drivers reporting poor mental health status. PMID:26316753

  8. 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.

  9. Criminal exposure.

    PubMed

    1999-09-01

    In August, an HIV-positive man plead guilty to sexually assaulting a 14-year-old boy. The sleeping boy awoke to find [name removed] sexually assaulting him, while watching a pornographic video. [Name removed] plead guilty to the assault with intent to rape a child. In addition, [name removed] received three counts of indecent assault and battery on a child, and exposure of pornographic material to a minor. [Name removed] will remain on probation for five years, although the prosecution had recommended sentencing [name removed] to four or five years in prison. The boy continues to be tested for HIV.

  10. 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

  11. 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

  12. 150-kD oxygen-regulated protein is expressed in human atherosclerotic plaques and allows mononuclear phagocytes to withstand cellular stress on exposure to hypoxia and modified low density lipoprotein.

    PubMed Central

    Tsukamoto, Y; Kuwabara, K; Hirota, S; Ikeda, J; Stern, D; Yanagi, H; Matsumoto, M; Ogawa, S; Kitamura, Y

    1996-01-01

    The 150-kD oxygen-regulated protein (ORP150) was initially characterized based on its selective expression in astrocytes subjected to oxygen deprivation (Kuwabara, K., M. Matsumoto, J. Ikeda, O. Hori, S. Ogawa, Y. Maeda, K. Kitagawa, N. Imuta, K. Kinoshita, D.M. Stern, et al. 1996. J. Biol. Chem. 279:5025-5032). We have found that exposure of cultured human aortic smooth muscle cells and mononuclear phagocytes (MPs) to hypoxia (pO2 approximately 12-14 torr) induces ORP150 transcripts and production of the antigen, whereas incubation with either hydrogen peroxide, sodium arsenite, heat shock, or 2-deoxyglucose was without effect. Tissue extracts prepared from human atherosclerotic lesions demonstrated expression of ORP150 mRNA and antigen, vs lack of ORP150 in samples from nonatherosclerotic areas. In situ hybridization using ORP150 riboprobes showed the mRNA to be predominantly [correction of predominately] present in macrophages in in atherosclerotic plaques. Furthermore, autoantibody to ORP150 was demonstrated in the serum of patients with severe atherosclerosis, consistent with inducible in vivo expression of ORP150. Introduction of antisense oligonucleotide for ORP150 selectively diminished hypoxia-mediated induction of ORP150 antigen and reduced the viability of hypoxic MPs, especially in the presence of modified (oxidized/acetylated) LDL. In support of a role for ORP150 in the MPs' response to the microenvironment of an atheroma, the presence of oxidized LDL enhanced by approximately 10-fold ORP150 expression in hypoxic cultures. These data indicate that cells of the atherosclerotic vessel wall express ORP150 as part of a protective mechanism, potentially triggered by local hypoxia/hypoxemia and augmented by modified lipoproteins. The presence of antibody to ORP150 in sera of patients with severe atherosclerosis emphasizes the possibility that ORP150 may be a marker of vascular pathology. PMID:8878445

  13. Exposure at the cell surface is required for gas3/PMP22 To regulate both cell death and cell spreading: implication for the Charcot-Marie-Tooth type 1A and Dejerine-Sottas diseases.

    PubMed

    Brancolini, C; Edomi, P; Marzinotto, S; Schneider, C

    2000-09-01

    Gas3/PMP22 is a tetraspan membrane protein highly expressed in myelinating Schwann cells. Point mutations in the gas3/PMP22 gene account for the dominant inherited peripheral neuropathies Charcot-Marie-Tooth type 1A disease (CMT1A) and Dejerine-Sottas syndrome (DSS). Gas3/PMP22 can regulate apoptosis and cell spreading in cultured cells. Gas3/PMP22 point mutations, which are responsible for these diseases, are defective in this respect. In this report, we demonstrate that Gas3/PMP22-WT is exposed at the cell surface, while its point-mutated derivatives are intracellularly retained, colocalizing mainly with the endoplasmic reticulum (ER). The putative retrieval motif present in the carboxyl terminus of Gas3/PMP22 is not sufficient for the intracellular sequestration of its point-mutated forms. On the contrary, the introduction of a retrieval signal at the carboxyl terminus of Gas3/PMP22-WT leads to its intracellular accumulation, which is accompanied by a failure to trigger cell death as well as by changes in cell spreading. In addition, by substituting the Asn at position 41 required for N-glycosylation, we provide evidence that N-glycosylation is required for the full effect on cell spreading, but it is not necessary for triggering cell death. In conclusion, we suggest that the DSS and the CMT1A neuropathies derived from point mutations of Gas3/PMP22 might arise, at the molecular level, from a reduced exposure of Gas3/PMP22 at the cell surface, which is required to exert its biological functions. PMID:10982389

  14. 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

  15. 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.

  16. 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.

  17. Primary Hepatic Carcinoid Tumor with Poor Outcome.

    PubMed

    Parkash, Om; Ayub, Adil; Naeem, Buria; Najam, Sehrish; Ahmed, Zubair; Jafri, Wasim; Hamid, Saeed

    2016-03-01

    Primary Hepatic Carcinoid Tumor (PHCT) represents an extremely rare clinical entity with only a few cases reported to date. These tumors are rarely associated with metastasis and surgical resection is usually curative. Herein, we report two cases of PHCT associated with poor outcomes due to late diagnosis. Both cases presented late with non-specific symptoms. One patient presented after a 2-week history of symptoms and the second case had a longstanding two years symptomatic interval during which he remained undiagnosed and not properly worked up. Both these cases were diagnosed with hepatic carcinoid tumor, which originates from neuroendocrine cells. Case 1 opted for palliative care and expired in one month’s time. Surgical resection was advised to the second case, but he left against medical advice. PMID:26975959

  18. 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.

  19. Color constancy enhancement under poor illumination.

    PubMed

    Liu, Jun; Shao, Zhenfeng; Cheng, Qimin

    2011-12-15

    In this Letter, the color constancy and its realization were studied and a novel color constancy image enhancement algorithm under poor illumination was presented. The purpose of this algorithm is to maintain the hue of an image during the processing so that the change of saturation can be minimized. The original image was first multiplied by a scale parameter obtained by the adaptive quadratic function to enhance the luminance, and then the edge details were restored by a shifting parameter. Numerical results of the Simon Fraser University (SFU) image database indicated that the proposed algorithm performed much better in preserving the hue and saturation and avoiding color distortion compared with the existing image enhancement algorithms. PMID:22179895

  20. Employees are paying for poor health habits.

    PubMed

    Cave, D G

    1992-08-01

    Realizing that corporate America may have limited control over how and when medical services are delivered, employers are beginning to attack the demand side of the health-care equation. That is, improving employee health status should result in a lower demand for medical services. However, to realize significant medical-claims savings, employers must encourage the least healthy employees both to enroll in work-site health-promotion programs and to permanently change their health-risk behaviors. One way to accomplish these objectives is to shift more financial risk onto employees by redesigning the company's medical benefit plan. As the 1990s progress and as medical costs continue to spiral upward, we are bound to observe greater employer involvement in employees' life-styles, both at work and at home. The bounds of discrimination and privacy laws will be tested as companies employ more restrictive policies and benefit plan designs to encourage employees to modify current poor-risk behaviors.

  1. Direct multiangle solution for poorly stratified atmospheres.

    PubMed

    Kovalev, Vladimir; Wold, Cyle; Petkov, Alexander; Hao, Wei Min

    2012-09-01

    The direct multiangle solution is considered, which allows improving the scanning lidar-data-inversion accuracy when the requirement of the horizontally stratified atmosphere is poorly met. The signal measured at zenith or close to zenith is used as a core source for extracting optical characteristics of the atmospheric aerosol loading. The multiangle signals are used as auxiliary data to extract the vertical transmittance profile from the zenith signal. Details of the retrieval methodology are considered that eliminate, or at least soften, some specific ambiguities in the multiangle measurements in horizontally heterogeneous atmospheres. Simulated and experimental elastic lidar data are presented that illustrate the essentials of the data-processing technique. Finally, the prospects of the utilization of high-spectral-resolution lidar in the multiangle mode are discussed. PMID:22945162

  2. Sun exposure at school.

    PubMed

    Moise, A F; Büttner, P G; Harrison, S L

    1999-08-01

    There is strong evidence that sun exposure during childhood and adolescence plays an important role in the etiology of skin cancer, in particular cutaneous melanoma. Between the age of 6 and 18, most children and adolescents will spend around 200 days per year at school and may receive a substantial fraction of their daily total solar ultraviolet radiation (UVR) exposure while at school. This study estimated the average daily erythemally effective dose of 70 grade 8 students from a high school in Townsville during 5 school days in July 1998. Through UV measurements of shade locations at the school and a combination of frequency counts and a questionnaire of grade 8 students, it was possible to determine the fraction of solar UVR reaching under the shade structures during lunch breaks and routine outdoor activities. Also, a routinely operating UV-Biometer provided the annual variation of the daily dose that was used to calculate exposure levels for the 70 students. Our results suggest that up to 47% of the daily total dose fell within the time periods where students were outdoors during school hours. For students not seeking shade structures during the breaks (which usually was the case when involved in sport activities such as basketball or soccer), the average daily dose could have been as high as 14 SED (standard erythemal dose). Using results from the questionnaire of 70 grade 8 students, their average annual dose while at school was 414 SED or 2 SED per school day. However, the distribution of average daily erythemal effective dose per grade 8 student over the whole year showed that on 31% of all school days in 1998, this dose was exceeded. Because most previous attempts to change arguably poor sun-protective behavior of young Australian children and adolescents at school showed little success, one way of decreasing the amount of harmful UVR reaching unprotected skin is the more careful design of shade structures at schools.

  3. Manganese exposure, essentiality & toxicity.

    PubMed

    Santamaria, A B

    2008-10-01

    Manganese (Mn) is an essential element present in all living organisms and is naturally present in rocks, soil, water, and food. Exposure to high oral, parenteral, or ambient air concentrations of Mn can result in elevations in Mn tissue levels and neurological effects. However, current understanding of the impact of Mn exposure on the nervous system leads to the hypothesis that there should be no adverse effects at low exposures, because Mn is an essential element; therefore, there should be some threshold for exposure above which adverse effects may occur and adverse effects may increase in frequency with higher exposures beyond that threshold. Data gaps regarding Mn neurotoxicity include what the clinical significance is of the neurobehavioural, neuropsychological, or neurological endpoints measured in many of the occupational studies that have evaluated cohorts exposed to relatively low levels of Mn. Specific early biomarkers of effect, such as subclinical neurobehavioural or neurological changes or magnetic resonance imaging (MRI) changes have not been established or validated for Mn, although some studies have attempted to correlate biomarkers with neurological effects. Experimental studies with rodents and monkeys provide valuable information about the absorption, bioavailability, and tissue distribution of various Mn compounds with different solubilities and oxidation states in different age groups. Studies have shown that rodents and primates maintain stable tissue manganese levels as a result of homeostatic mechanisms that tightly regulate absorption and excretion. In addition, physiologically based pharmacokinetic (PBPK) models are being developed to provide for the ability to conduct route-to-route extrapolations, evaluate nasal uptake to the CNS, and evaluate lifestage differences in Mn pharmacokinetics. Such models will facilitate more rigorous quantitative analysis of the available pharmacokinetic data for Mn and will be used to identify situations

  4. Poor education linked with teen pregnancies.

    PubMed

    Westall, J

    1997-02-22

    Two reports concerning socioeconomic factors associated with adolescent pregnancy have been released: a study from the NHS Centre for Reviews and Dissemination at the University of York; and a survey from the Alan Guttmacher Institute, a non-profit reproductive health analysis organization in New York. The first report associates truancy, low academic achievement and poor sex education with the high pregnancy rate in Britain among women 15-19 years old. The rate is the highest in western Europe, although the rate of conceptions in Britain among women 16-19 years old has declined since 1990 and is currently 56.8 per 1000. For girls under 16 years old, a group targeted by the British government's Health of the Nation strategy to achieve a conception rate of 4.8 per 1000 by the year 2000, the rate has remained steady for the last 20 years and stands at 8.3 per 1000. The report calls for better school-based sex education and for improved access to confidential contraceptive services for young people. The second report, an international survey, shows that the number of teenage pregnancies worldwide is declining (although 15 million babies, 10% unplanned, are born annually to teenage mothers), and that women with a higher education level tend to delay marriage and childbearing. A figure compares the percentages of women 20-24 years old who gave birth by age 20 for 4 educational levels (less than 7 years, greater than or equal to 7 years, less than 12 years, greater than or equal to 12 years) for Ghana, Kenya, Zimbabwe, Bangladesh, Egypt, Indonesia, the Philippines, Bolivia, Brazil, Columbia, Mexico, France, Japan, and the United States. Teenage pregnancy in both reports was associated with poor social, economic, and health outcomes for mother and child. According to the second report, the risk of maternal death during childbirth is 2-4 times greater for mothers 17 and younger, in comparison to mothers age 20 and older. Dr. Kathleen Kiernan, a senior research fellow at

  5. Kinematics of AWM and MKW Poor Clusters

    NASA Astrophysics Data System (ADS)

    Koranyi, Daniel M.; Geller, Margaret J.

    2002-01-01

    We have measured 1365 redshifts to a limiting magnitude of R~15.5 in 15 AWM/MKW clusters and have collected another 203 from the literature in MKW 4s, MKW 2, and MKW 2s. In AWM 7 we have extended the redshift sample to R~18 in the cluster center. We have identified 704 cluster members in 17 clusters; 201 are newly identified. We summarize the kinematics and distributions of the cluster galaxies and provide an initial discussion of substructure, mass and luminosity segregation, spectral segregation, velocity-dispersion profiles, and the relation of the central galaxy to global cluster properties. We compute optical mass estimates, which we compare with X-ray mass determinations from the literature. The clusters are in a variety of dynamical states, reflected in the three classes of behavior of the velocity-dispersion profile in the core: rising, falling, or flat/ambiguous. The velocity dispersion of the emission-line galaxy population significantly exceeds that of the absorption-line galaxies in almost all of the clusters, and the presence of emission-line galaxies at small projected radii suggests continuing infall of galaxies onto the clusters. The presence of a cD galaxy does not constrain the global cluster properties; these clusters are similar to other poor clusters that contain no cD. We use the similarity of the velocity-dispersion profiles at small radii and the cD-like galaxies' internal velocity dispersions to argue that cD formation is a local phenomenon. Our sample establishes an empirical observational baseline of poor clusters for comparison with simulations of similar systems. Observations reported in this paper were obtained at the Multiple Mirror Telescope Observatory, a facility operated jointly by the University of Arizona and the Smithsonian Institution; at the Whipple Observatory, a facility operated jointly by the Smithsonian Astrophysical Observatory and Harvard University; and at the WIYN Observatory, a joint facility of the University of

  6. Aggregating poor and near-poor elderly under different resource definitions.

    PubMed

    Rendall, M S

    1996-07-01

    The large number of near-poor relative to poor elderly persons in the United States may be recharacterized as a high-prevalence, low-intensity type of poverty. The present study investigates how this characterization is affected by accounting for assets and non-cash transfers in addition to cash income in resources available for current-year consumption. The Foster, Greer, Thorbecke (FGT) poverty index is used to separately and jointly analyze prevalence and intensity of poverty. Estimation is from 1984 Survey of Income and Program Participation data. Adding the annuity value of assets removes many elderly persons from the ranks of the poor and near-poor, while adding non-cash transfers moves many elderly persons from poverty into near-poverty. Their combined effect reinforces a high-prevalence, low-intensity characterization of poverty. Large total poverty reduction effects are missed by income-only resource definition, and large poverty-intensity reduction effects are missed by prevalence-only aggregation.

  7. Discrepantly poor verbal skills in poor readers: a failure of learning or ability?

    PubMed

    Langdon, D W; Rosenblatt, N; Mellanby, J H

    1998-05-01

    Poor verbal skills in poor readers have long been reported in the literature. There have been many attempts to understand the interaction between poor verbal ability and poor verbal achievement. The methodological problems are considerable, including the measurement of verbal ability, which has been confounded by previous learning. A new reasoning test, the VESPAR, has been designed to measure novel problem solving and thus to be less reliant on acquired verbal skills. One hundred and seventy 14-year-olds completed the VESPAR, the Cognitive Abilities Test (CAT) and a single-word reading test. Overall, verbal scores were weaker than spatial scores. A subgroup of 38 pupils with particularly marked discrepancies between verbal and non-verbal CAT was identified. The especially discrepant pupils were matched with other non-discrepant pupils from the year group for either verbal or non-verbal CAT. The discrepant group's reading was at the same level as the matched verbal CAT group. However, the primary verbal ability of the discrepancy group, as measured on the VESPAR, was greater than the matched verbal CAT group. This raises the possibility that CAT- but not VESPAR-discrepant pupils may be at particular risk of under-achievement in the verbal domain.

  8. 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

  9. Toward ab initio extremely metal poor stars

    NASA Astrophysics Data System (ADS)

    Ritter, Jeremy S.; Safranek-Shrader, Chalence; Milosavljević, Miloš; Bromm, Volker

    2016-09-01

    Extremely metal poor stars have been the focus of much recent attention owing to the expectation that their chemical abundances can shed light on the metal and dust yields of the earliest supernovae. We present our most realistic simulation to date of the astrophysical pathway to the first metal enriched stars. We simulate the radiative and supernova hydrodynamic feedback of a 60 M⊙ Population III star starting from cosmological initial conditions realizing Gaussian density fluctuations. We follow the gravitational hydrodynamics of the supernova remnant at high spatial resolution through its freely-expanding, adiabatic, and radiative phases, until gas, now metal-enriched, has resumed runaway gravitational collapse. Our findings are surprising: while the Population III progenitor exploded with a low energy of 1051 erg and injected an ample metal mass of 6 M⊙, the first cloud to collapse after the supernova explosion is a dense surviving primordial cloud on which the supernova blast wave deposited metals only superficially, in a thin, unresolved layer. The first metal-enriched stars can form at a very low metallicity, of only 2 - 5 × 10-4 Z⊙, and can inherit the parent cloud's highly elliptical, radially extended orbit in the dark matter gravitational potential.

  10. Carbon balance of a temperate poor fen

    NASA Astrophysics Data System (ADS)

    Carroll, Paul; Crill, Patrick

    1997-09-01

    The dynamic carbon balance of a southeastern New Hampshire wetland was constructed for the 1994 growing season using a light-dark box sampling method. Net ecosystem exchange (NEE) (n = 414) and ecosystem respiration (n=234) measurements were made at the 1.7 ha Sphagnum spp. dominated poor fen. The NEE rates ranged from -192 to 492 mg C m-2 h-1 and the ecosystem respiration measurements were between -10 and -365 mg C m-2 h-1. The negative values represent a loss of carbon from the wetland system. NEE and respiration data were used to derive photosynthesis rates of the vegetation at the study site. A simple model, using hourly averages of photosynthetically active radiation, and air and soil temperatures to generate hourly rates of photosynthesis and respiration, was constructed to interpolate the carbon cycling rates at this fen through the entire 1994 growing season. Results of the carbon balance model suggest that the wetland lost an estimated 145 g C m-2 for the 9 month modeling period (April through December). The 1994 climate season was warmer (+1.15°C/month)and drier (-12.3 cm) than the 30 year normals for Durham, New Hampshire, the nearest meteorological station. These data suggest that if future climate change brings about warmer temperatures and lower water tables in peatland soils, positive climatic feedback leading to substantial releases of CO2 from boreal and subarctic peatlands is probable.

  11. 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.

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

    PubMed

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

    2015-11-19

    Economic transitions in the era of globalization warrant a fresh look at the neurological risks associated with environmental change. These are driven by industrial expansion, transfer and mobility of goods, climate change and population growth. In these contexts, risk of infectious and non-infectious diseases are shared across geographical boundaries. In low- and middle-income countries, the risk of environmentally mediated brain disease is augmented several fold by lack of infrastructure, poor health and safety regulations, and limited measures for environmental protection. Neurological disorders may occur as a result of direct exposure to chemical and/or non-chemical stressors, including but not limited to, ultrafine particulate matters. Individual susceptibilities to exposure-related diseases are modified by genetic, epigenetic and metagenomic factors. The existence of several uniquely exposed populations, including those in the areas surrounding the Niger Delta or north western Amazon oil operations; those working in poorly regulated environments, such as artisanal mining industries; or those, mostly in sub-Saharan Africa, relying on cassava as a staple food, offers invaluable opportunities to advance the current understanding of brain responses to environmental challenges. Increased awareness of the brain disorders that are prevalent in low- and middle-income countries and investments in capacity for further environmental health-related research are positive steps towards improving human health. PMID:26580326

  13. 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.

  14. Deep Imaging of Extremely Metal-Poor Galaxies

    NASA Astrophysics Data System (ADS)

    Corbin, Michael

    2006-07-01

    Conflicting evidence exists regarding whether the most metal-poor and actively star-forming galaxies in the local universe such as I Zw 18 contain evolved stars. We propose to help settle this issue by obtaining deep ACS/HRC U, narrow-V, I, and H-alpha images of nine nearby {z < 0.01} extremely metal-poor {12 + O/H < 7.65} galaxies selected from the Sloan Digital Sky Survey. These objects are only marginally resolved from the ground and appear uniformly blue, strongly motivating HST imaging. The continuum images will establish: 1.} If underlying populations of evolved stars are present, by revealing the objects' colors on scales 10 pc, and 2.} The presence of any faint tidal features, dust lanes, and globular or super star clusters, all of which constrain the objects' evolutionary states. The H-alpha images, in combination with ground-based echelle spectroscopy, will reveal 1.} Whether the objects are producing "superwinds" that are depleting them of their metals; ground-based images of some of them indeed show large halos of ionized gas, and 2.} The correspondence of their nebular and stellar emission on scales of a few parsecs, which is important for understanding the "feedback" process by which supernovae and stellar winds regulate star formation. One of the sample objects, CGCG 269-049, lies only 2 Mpc away, allowing the detection of individual red giant stars in it if any are present. We have recently obtained Spitzer images and spectra of this galaxy to determine its dust content and star formation history, which will complement the proposed HST observations. [NOTE: THIS PROPOSAL WAS REDUCED TO FIVE ORBITS, AND ONLY ONE OF THE ORIGINAL TARGETS, CGCG 269-049, AFTER THE PHASE I REVIEW

  15. 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.

  16. Monitoring phthalate exposure in humans.

    PubMed

    Latini, Giuseppe

    2005-11-01

    The dialkyl- or alkyl/aryl esters of 1,2-benzenedicarboxylic acid, commonly known as phthalates, are high-production-volume synthetic chemicals and ubiquitous environmental contaminants because of their use in plastics and other common consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is the most abundant phthalate in the environment. Humans are exposed to these compounds through ingestion, inhalation, and dermal exposure for their whole lifetime, since the intrauterine life. Public and scientific concern has increased in recent years about the potential health risks associated with exposure to phthalates. The main focus has moved away from the hepatotoxic effects to the endocrine disrupting potency of these chemicals. To date, although the consistent toxicologic data on phthalates is suggestive, information on sources and pathways of human exposure to phthalates is limited. Recently, exposure to phthalates has been assessed by analyzing urine for their metabolites. This approach is contrary to the determination of the parent phthalates in air, water and foodstuff and not subject to contamination. Furthermore, these metabolites and the parent phthalates are considered the toxic species. However, accurate methods and models for measuring the amount of phthalates absorbed by the various pathways of exposure have to be developed. In fact, a frequent biological monitoring of phthalates in body fluids and tissues would be highly advisable, both in helping physicians to perform health risk assessments for exposure in the general population and in guiding governments to provide regulations concerning the maximum allowed concentrations in the environment, plasticized products, medications and medical equipment.

  17. 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

  18. 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. PMID:25284196

  19. Efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide added to insulin therapy in poorly regulated patients with type 1 diabetes—a protocol for a randomised, double-blind, placebo-controlled study: The Lira-1 study

    PubMed Central

    Dejgaard, Thomas Fremming; Knop, Filip Krag; Tarnow, Lise; Frandsen, Christian Seerup; Hansen, Tanja Stenbæk; Almdal, Thomas; Holst, Jens Juul; Madsbad, Sten; Andersen, Henrik Ullits

    2015-01-01

    Introduction Intensive insulin therapy is recommended for the treatment of type 1 diabetes (T1D). Hypoglycaemia and weight gain are the common side effects of insulin treatment and may reduce compliance. In patients with insulin-treated type 2 diabetes, the addition of glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy has proven effective in reducing weight gain and insulin dose. The present publication describes a protocol for a study evaluating the efficacy and safety of adding a GLP-1RA to insulin treatment in overweight patients with T1D in a randomised, double-blinded, controlled design. Methods and analysis In total, 100 patients with type 1 diabetes, poor glycaemic control (glycated haemoglobin (HbA1c) >8%) and overweight (body mass index >25 kg/m2) will be randomised to either liraglutide 1.8 mg once daily or placebo as an add-on to intensive insulin therapy in this investigator initiated, double-blinded, placebo-controlled parallel study. The primary end point is glycaemic control as measured by changes in HbA1c. Secondary end points include changes in the insulin dose, hypoglyacemic events, body weight, lean body mass, fat mass, food preferences and adverse events. Glycaemic excursions, postprandial glucagon levels and gastric emptying rate during a standardised liquid meal test will also be studied. Ethics and dissemination The study is approved by the Danish Medicines Authority, the Regional Scientific-Ethical Committee of the Capital Region of Denmark and the Data Protection Agency. The study will be carried out under the surveillance and guidance of the good clinical practice (GCP) unit at Copenhagen University Hospital Bispebjerg in accordance with the ICH-GCP guidelines and the Helsinki Declaration. Trial registration number NCT01612468. PMID:25838513

  20. RNASeq in C. elegans Following Manganese Exposure.

    PubMed

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

    2015-08-06

    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.

  1. Childhood Absence Epilepsy: Poor Attention Is More Than Seizures

    MedlinePlus

    ... Spencer, MD Steven Karceski, MD Childhood absence epilepsy Poor attention is more than seizures Liu Lin Thio, ... of this article is prohibited. Childhood absence epilepsy: Poor attention is more than seizures Liu Lin Thio ...

  2. A Problem Solving Framework for Managing Poor Readers in Classrooms.

    ERIC Educational Resources Information Center

    Beck, Judith S.

    1988-01-01

    Points out that poor readers may exhibit behavioral, cognitive, and emotional problems. Offers a problem-solving framework for intervention in poor readers' nonacademic problems, and describes several possible types of intervention. (ARH)

  3. Potential operator exposure to procymidone in greenhouses.

    PubMed

    Capri, E; Alberici, R; Glass, C R; Minuto, G; Trevisan, M

    1999-10-01

    Recent legislation in the European Union requires regulators of member states to carry out risk assessments using data for actual or potential operator exposure, or estimates of exposure from models. However, the existing models have few datasets from studies carried out on greenhouse or indoor crops, particularly in southern Europe. In this study potential dermal and inhalatory exposures were measured in two trials in Italian greenhouses. The total potential dermal operator exposure of the applicator, measured with a whole-body passive dosimetry method, was 15.4 and 37.1 mL/h of the diluted pesticide mixture. The majority of the contamination was on the hands and on the lower part of the coverall. Approximately 0. 003% of the active ingredient (ai) applied to the crop area contaminated the coverall worn by the operator. The potential dermal exposure during the mixing and loading phase accounted for 6-8% of the total potential dermal exposure during the whole process. Inhalation exposure accounted for only 0.05-0.07% of the total potential operator exposure. Model predictions of the potential operator exposure using a modified version of the German model overestimate the mixing-loading exposure while underestimating the application exposure. These data are evidence that the estimation coefficient set for hand-held application to ornamental and horticultural crops may be inadequate for the agronomic conditions of southern Europe. PMID:10552831

  4. 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…

  5. 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…

  6. Very Early Language Skills of Fifth-Grade Poor Comprehenders

    ERIC Educational Resources Information Center

    Justice, Laura; Mashburn, Andrew; Petscher, Yaacov

    2013-01-01

    This study tested the theory that future poor comprehenders would show modest but pervasive deficits in both language comprehension and production during early childhood as compared with future poor decoders and typical readers. Using an existing database (NICHD ECCRN), fifth-grade students were identified as having poor comprehension skills…

  7. 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…

  8. 30 CFR 62.130 - Permissible exposure level.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REGULATIONS OCCUPATIONAL NOISE EXPOSURE § 62.130 Permissible exposure level. (a) The mine operator must assure... must use all feasible engineering and administrative controls to reduce the miner's noise exposure to... with § 62.150 of this part. When a mine operator uses administrative controls to reduce a...

  9. Environmental exposures, socioeconomics, disparities, and the kidneys.

    PubMed

    Said, Sarmad; Hernandez, German T

    2015-01-01

    Kidney disease disproportionately affects racial and ethnic minority populations, the poor, and the socially disadvantaged. The excess risk of kidney disease among minority and disadvantaged populations can only be partially explained by an excess of diabetes, hypertension, and poor access to preventive care. Disparities in the environmental exposure to nephrotoxicants have been documented in minority and disadvantaged populations and may explain some of the excess risk of kidney disease. High-level environmental and occupational exposure to lead, cadmium, and mercury are known to cause specific nephropathies. However, there is growing evidence that low-level exposures to heavy metals may contribute to the development of CKD and its progression. In this article, we summarize the excess risk of environmental exposures among minority and disadvantaged populations. We also review the epidemiologic and clinical data linking low-level environmental exposure to lead, cadmium, and mercury to CKD and its progression. Finally, we briefly describe Mesoamerican nephropathy, an epidemic of CKD affecting young men in Central America, which may have occupational and environmental exposures contributing to its development.

  10. 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...

  11. 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...

  12. Access to orphan drugs despite poor quality of clinical evidence

    PubMed Central

    Dupont, Alain G; Van Wilder, Philippe B

    2011-01-01

    AIM We analysed the Belgian reimbursement decisions of orphan drugs as compared with those of innovative drugs for more common but equally severe diseases, with special emphasis on the quality of clinical evidence. METHODS Using the National Health Insurance Agency administrative database, we evaluated all submitted orphan drug files between 2002 and 2007. A quality analysis of the clinical evidence in the orphan reimbursement files was performed. The evaluation reports of the French ‘Haute Autorité de Santé’, including the five-point scale parameter ‘Service Médical Rendu (SMR), were examined to compare disease severity. Chi-squared tests (at P < 0.05 significance level) were used to compare the outcome of the reimbursement decisions between orphan and non-orphan innovative medicines. RESULTS Twenty-five files of orphan drugs and 117 files of non-orphan drugs were evaluated. Twenty-two of 25 (88%) submissions of orphan drugs were granted reimbursement as opposed to 74 of the 117 (63%) non-orphan innovative medicines (P = 0.02). Only 52% of the 25 orphan drug files included a randomized controlled trial as opposed to 84% in a random control sample of 25 non-orphan innovative submissions (P < 0.01). The duration of drug exposure was in most cases far too short in relation to the natural history of the disease. CONCLUSIONS Orphan drug designation predicts reimbursement despite poor quality of clinical evidence. The evidence gap at market authorization should be reduced by post-marketing programmes, in which the centralized regulatory and the local reimbursement authorities collaborate in an efficient way across the European Union member states. PMID:21395641

  13. 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

  14. 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

  15. Posttraumatic stress disorder, poor physical health and substance use behaviors in a national trauma-exposed sample.

    PubMed

    Del Gaizo, Ariel L; Elhai, Jon D; Weaver, Terri L

    2011-08-15

    Both experiencing a traumatic event and PTSD are related to physical health problems (e.g., Schnurr and Jankowski, 1999) and health-risk behavior (e.g., Stewart, 1996). Using structural equation modeling analyses, we examined the interrelationships among number of distinct traumatic event exposures, PTSD diagnosis, physical health, and substance use behavior using epidemiological data from the National Comorbidity Survey Replication (NCS-R; Kessler et al., 2004). Results provide some evidence that PTSD mediates the relationship between: (a) number of distinct traumatic event exposures and poor physical health defined by clusters of difficulties with gastrointestinal, musculoskeletal, and/or cardiovascular health, and (b) number of distinct traumatic event exposures and substance use behaviors. However, substance use behaviors did not significantly mediate the relationship between PTSD and poor physical health.

  16. Formaldehyde exposure and acute health effects study

    SciTech Connect

    Quackenboss, J.J.; Lebowitz, M.D.; Michaud, J.P.; Bronnimann, D. )

    1989-01-01

    To assess the effects of formaldehyde exposures on health, exposure groups were defined using baseline exposure and health questionnaires. Formaldehyde concentrations were poorly correlated with these exposure classifications, perhaps due to the time delay between classification and monitoring. The 151 households reported here had a mean HCHO concentration of 35 (S.E. 1.5 and median 30) {mu}g/m{sup 3}. Passive samplers prepared in our lab were calibrated in a chamber to derive an estimated sampling rate of 0.311 {mu}g/(mg {center dot} m{sup {minus}3} {center dot} hr). They were also compared to commercially available samplers inside of the homes, with a correlation coefficient of 0.896 and mean difference of 2.6 {mu}g/m{sup 3}. In this report of initial findings from an ongoing study, daily symptoms and peak expiratory flow measurements were compared with an HCHO exposure classification based on the median measured concentrations. None of the symptoms groups were related to HCHO exposure when controlling for age and sex. There was a significant relationship between HCHO exposure and variability in peak expiratory flows that was dependent on age group. It may be especially important to assess the variability in reactive individuals and children to determine the short-term effects of HCHO exposures and possible long-term consequences.

  17. 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.

  18. Fluoxetine Exposure during Adolescence Alters Responses to Aversive Stimuli in Adulthood

    PubMed Central

    Alcantara, Lyonna F.; Warren, Brandon L.; Riggs, Lace M.; Parise, Eric M.; Vialou, Vincent; Wright, Katherine N.; Dayrit, Genesis; Nieto, Steven J.; Wilkinson, Matthew B.; Lobo, Mary K.; Neve, Rachael L.; Nestler, Eric J.; Bolaños-Guzmán, Carlos A.

    2014-01-01

    The mechanisms underlying the enduring neurobiological consequences of antidepressant exposure during adolescence are poorly understood. Here, we assessed the long-term effects of exposure to fluoxetine (FLX), a selective serotonin reuptake inhibitor, during adolescence on behavioral reactivity to emotion-eliciting stimuli. We administered FLX (10 mg/kg, bi-daily, for 15 d) to male adolescent [postnatal day 35 (P35) to P49] C57BL/6 mice. Three weeks after treatment (P70), reactivity to aversive stimuli (i.e., social defeat stress, forced swimming, and elevated plus maze) was assessed. We also examined the effects of FLX on the expression of extracellular signal-regulated kinase (ERK) 1/2-related signaling within the ventral tegmental area (VTA) of adolescent mice and Sprague Dawley rats. Adolescent FLX exposure suppressed depression-like behavior, as measured by the social interaction and forced swim tests, while enhancing anxiety-like responses in the elevated plus maze in adulthood. This complex behavioral profile was accompanied by decreases in ERK2 mRNA and protein phosphorylation within the VTA, while stress alone resulted in opposite neurobiological effects. Pharmacological (U0126) inhibition, as well as virus-mediated downregulation of ERK within the VTA mimicked the antidepressant-like profile observed after juvenile FLX treatment. Conversely, overexpression of ERK2 induced a depressive-like response, regardless of FLX pre-exposure. These findings demonstrate that exposure to FLX during adolescence modulates responsiveness to emotion-eliciting stimuli in adulthood, at least partially, via long-lasting adaptations in ERK-related signaling within the VTA. Our results further delineate the role ERK plays in regulating mood-related behaviors across the lifespan. PMID:24431458

  19. 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. PMID:25735858

  20. Combating poor-quality anti-malarial medicines: a call to action.

    PubMed

    Bassat, Quique; Tanner, Marcel; Guerin, Philippe J; Stricker, Kirstin; Hamed, Kamal

    2016-01-01

    The circulation of poor-quality medicines continues to undermine the fight against many life-threatening diseases. Anti-malarial medicines appear to have been particularly compromised and present a major public health threat in malaria-endemic countries, negatively affecting individuals and their communities. Concerted collaborative efforts are required from global, regional and national organizations, involving the public and private sectors, to address the problem. While many initiatives are underway, a number of unmet needs deserve urgent and increased multisector attention. At the global level, there is a need for an international public health legal framework or treaty on poor-quality medicines, with statutes suitable for integration into national laws. In addition, increased international efforts are required to strengthen the governance of global supply chains and enhance cooperation between national medicine regulation authorities and law enforcement bodies. Increased investment is needed in innovative technologies that will enable healthcare teams to detect poor-quality medicines at all levels of the supply chain. At the regional level, a number of initiatives would be beneficial-key areas are standardization, simplification, and reciprocal recognition of registration processes and development of quality control capacity in regional centres of excellence that are better aligned with public health needs; improved surveillance methods and creation of a framework for compulsory and transparent reporting of poor-quality medicines; additional support for national medicine regulation authorities and other national partner authorities; and an increase in support for regional laboratories to boost their capabilities in detecting poor-quality medicines. It is vital that all stakeholders involved in efforts against poor-quality anti-malarial medicines extend and strengthen their actions in these critical areas and thus effectively support global health development

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

    NASA Astrophysics Data System (ADS)

    Shafiq, M. Najeeb

    2010-02-01

    A targeted educational voucher scheme (TEVS) is often proposed for the poor in developing countries. Essentially, TEVS involves issuing vouchers to poor households, thus enabling them to pay tuition and fees for their children's schooling at participating non-public schools. However, little is known about TEVS' design in developing countries. This article provides the foundation for constructing a TEVS and conducting subsequent scientific evaluations to support, modify or oppose such a system. Specifically, this article uses three policy instruments to design a TEVS: regulation, support services and finance. Regulation here refers to the rules that must be adhered to by participating households, children and schools. Support services refer to services facilitating the participation of children, households, schools, and financial and political supporters. Finance refers to the value of each voucher, total TEVS costs and sources of finance.

  2. Expression of c-myc and induction of DNA synthesis by platelet-poor plasma in human diploid fibroblasts

    SciTech Connect

    Ferrari, S.; Calabretta, B.; Battini, R.; Cosenza, S.C.; Owen, T.A.; Soprano, K.J.; Baserga, R. )

    1988-01-01

    When WI-38 human diploid fibroblasts become confluent, they stop synthesizing DNA and dividing. Addition of serum causes the quiescent cell to reenter the cell cycle. Prolonged quiescence after confluence decreases and delays the response to serum. For a few days after reaching confluence. WI-38 cells also respond to platelet-poor plasma. During this period, although not cycling, WI-38 cells still express c-myc and other growth-regulated genes, as measured by steady-state RNA levels. If the quiescence is prolonged further, c-myc expression (and that of two other growth-regulated genes) is no longer detectable, and its disappearance coincides with a loss of response to platelet-poor plasma. These results suggest that, also under physiological conditions, the expression of c-myc and other growth-regulated genes can cooperate with platelet-poor plasma in inducing cellular DNA synthesis in human diploid fibroblasts.

  3. 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

  4. Medium wave exposure characterisation using exposure quotients.

    PubMed

    Paniagua, Jesús M; Rufo, Montaña; Jiménez, Antonio; Antolín, Alicia; Pinar, Iván

    2010-06-01

    One of the aspects considered in the International Commission on Non-Ionizing Radiation Protection guidelines is that, in situations of simultaneous exposure to fields of different frequencies, exposure quotients for thermal and electrical stimulation effects should be examined. The aim of the present work was to analyse the electromagnetic radiation levels and exposure quotients for exposure to multiple-frequency sources in the vicinity of medium wave radio broadcasting antennas. The measurements were made with a spectrum analyser and a monopole antenna. Kriging interpolation was used to prepare contour maps and to estimate the levels in the towns and villages of the zone. The results showed that the exposure quotient criterion based on electrical stimulation effects to be more stringent than those based on thermal effects or power density levels. Improvement of dosimetry evaluations requires the spectral components of the radiation to be quantified, followed by application of the criteria for exposure to multiple-frequency sources. PMID:20159912

  5. 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.

  6. Human exposure to phthalates via consumer products.

    PubMed

    Schettler, Ted

    2006-02-01

    Phthalate exposures in the general population and in subpopulations are ubiquitous and widely variable. Many consumer products contain specific members of this family of chemicals, including building materials, household furnishings, clothing, cosmetics, pharmaceuticals, nutritional supplements, medical devices, dentures, children's toys, glow sticks, modelling clay, food packaging, automobiles, lubricants, waxes, cleaning materials and insecticides. Consumer products containing phthalates can result in human exposures through direct contact and use, indirectly through leaching into other products, or general environmental contamination. Historically, the diet has been considered the major source of phthalate exposure in the general population, but all sources, pathways, and their relative contributions to human exposures are not well understood. Medical devices containing di-(2-ethylhexyl) phthalate are a source of significant exposure in a susceptible subpopulation of individuals. Cosmetics, personal care products, pharmaceuticals, nutritional supplements, herbal remedies and insecticides, may result in significant but poorly quantified human exposures to dibutyl phthalate, diethyl phthalate, or dimethyl phthalate. Oven baking of polymer clays may cause short-term, high-level inhalation exposures to higher molecular weight phthalates. PMID:16466533

  7. 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.

  8. Cardiorespiratory effects of nicotine exposure during development.

    PubMed

    Hafström, Ola; Milerad, Joseph; Sandberg, Kenneth L; Sundell, Håkan W

    2005-11-15

    Exposure to tobacco smoke is a major risk factor for the sudden infant death syndrome. Nicotine is thought to be the ingredient in tobacco smoke that is responsible for a multitude of cardiorespiratory effects during development, and pre- rather than postnatal exposure is considered to be most detrimental. Nicotine interacts with endogenous acetylcholine receptors in the brain and lung, and developmental exposure produces structural changes as well as alterations in neuroregulation. Abnormalities have been described in sympathicovagal balance, arousal threshold and latency, breathing pattern at rest and apnea frequency, ventilatory response to hyperoxia or hypoxia, heart rate regulation and ability to autoresuscitate during severe hypoxia. This review discusses studies performed on infants of smoking mothers and nicotine-exposed animals yielding varying and sometimes inconsistent results that may be due to differences in experimental design, species and the dose of exposure. Taken together however, developmental nicotine exposure appears to induce vulnerability during hypoxia and a potential inability to survive severe asphyxia.

  9. OCCUPATIONAL EXPOSURE TO EXTERNAL RADIATION IN SWITZERLAND.

    PubMed

    Mayer, S; Baechler, S; Damet, J; Elmiger, R; Frei, D; Giannini, S; Leupin, A; Sarott, F; Schuh, R

    2016-09-01

    Individual monitoring for both external and internal exposures is well regulated in Switzerland. The article gives an overview on the occupational exposure to external radiation of workers based on the data collected in the Swiss national dose registry (NDR) in 2013. The NDR records the monthly doses of radiation workers since the introduction of ICRP 60 recommendations and is manifested in the Swiss ordinance since 1994. Annual dose limits for effective dose are typically exceeded once a year in Switzerland, mostly in medicine. The NDR is a useful optimisation tool to identify and characterise areas with the highest exposures. While exceeded dose limits were often related to accidental acute exposure in the past, they are now more related to continuous exposure during normal work, especially in medicine. PMID:27012882

  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. Kinematics and dynamics of the MKW/AWM poor clusters

    NASA Astrophysics Data System (ADS)

    Beers, Timothy C.; Kriessler, Jeffrey R.; Bird, Christina M.; Huchra, John P.

    1995-03-01

    We report 472 new redshifts for 416 galaxies in the regions of the 23 poor clusters of galaxies originally identified by Morgan, Kayser, and White (MKW), and Albert, White, and Morgan (AWM). Eighteen of the poor clusters now have 10 or more available redshifts within 1.5/h Mpc of the central galaxy; 11 clusters have at least 20 available redshifts. Based on the 21 clusters for which we have sufficient velocity information, the median velocity scale is 336 km/s, a factor of 2 smaller than found for rich clusters. Several of the poor clusters exhibit complex velocity distributions due to the presence of nearby clumps of galaxies. We check on the velocity of the dominant galaxy in each poor cluster relative to the remaining cluster members. Significantly high relative velocities of the dominant galaxy are found in only 4 of 21 poor clusters, 3 of which we suspect are due to contamination of the parent velocity distribution. Several statistical tests indicate that the D/cD galaxies are at the kinematic centers of the parent poor cluster velocity distributions. Mass-to-light ratios for 13 of the 15 poor clusters for which we have the required data are in the range 50 less than or = M/LB(0) less than or = 200 solar mass/solar luminosity. The complex nature of the regions surrounding many of the poor clusters suggests that these groupings may represent an early epoch of cluster formation. For example, the poor clusters MKW7 and MKWS are shown to be gravitationally bound and likely to merge to form a richer cluster within the next several Gyrs. Eight of the nine other poor clusters for which simple two-body dynamical models can be carried out are consistent with being bound to other clumps in their vicinity. Additional complex systems with more than two gravitationally bound clumps are observed among the poor clusters.

  12. Understanding existing exposure situations.

    PubMed

    Lecomte, J-F

    2016-06-01

    International Commission on Radiological Protection (ICRP) Publication 103 removed the distinction between practices and interventions, and introduced three types of exposure situation: existing, planned, and emergency. It also emphasised the optimisation principle in connection with individual dose restrictions for all controllable exposure situations. Existing exposure situations are those resulting from sources, natural or man-made, that already exist when a decision on control has to be taken. They have common features to be taken into account when implementing general recommendations, such as: the source may be difficult to control; all exposures cannot be anticipated; protective actions can only be implemented after characterisation of the exposure situation; time may be needed to reduce exposure below the reference level; levels of exposure are highly dependent on individual behaviour and present a wide spread of individual dose distribution; exposures at work may be adventitious and not considered as occupational exposure; there is generally no potential for accident; many stakeholders have to be involved; and many factors need to be considered. ICRP is currently developing a series of reports related to the practical implementation of Publication 103 to various existing exposure situations, including exposure from radon, exposure from cosmic radiation in aviation, exposure from processes using naturally occurring radioactive material, and exposure from contaminated sites due to past activities. PMID:26975365

  13. 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...

  14. A comparison of the language skills of ELLs and monolinguals who are poor decoders, poor comprehenders, or normal readers.

    PubMed

    Geva, Esther; Massey-Garrison, Angela

    2013-01-01

    The overall objective of this article is to examine how oral language abilities relate to reading profiles in English language learners (ELLs) and English as a first language (EL1) learners, and the extent of similarities and differences between ELLs and EL1s in three reading subgroups: normal readers, poor decoders, and poor comprehenders. The study included 100 ELLs and 50 EL1s in Grade 5. The effect of language group (ELL/EL1) and reading group on cognitive and linguistic skills was examined. Except for vocabulary, there was no language group effect on any measure. However, within ELL and EL1 alike, significant differences were found between reading groups: Normal readers outperformed the two other groups on all the oral language measures. Distinct cognitive and linguistic profiles were associated with poor decoders and poor comprehenders, regardless of language group. The ELL and EL1 poor decoders outperformed the poor comprehenders on listening comprehension and inferencing. The poor decoders displayed phonological-based weaknesses, whereas the poor comprehenders displayed a more generalized language processing weakness that is nonphonological in nature. Regardless of language status, students with poor decoding or comprehension problems display difficulties with various aspects of language.

  15. 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.

  16. Patterns of Risk: The Nutritional Status of the Rural Poor.

    ERIC Educational Resources Information Center

    Shotland, Jeffrey; Loonin, Deanne

    Nutrition and health are underlying influences to education performance. This report is a collection and analysis of data on nutrition and the rural poor in the United States. It presents an empirical assessment of critical nutritional and social-service problems experienced by the rural poor population. The first section of the report uses data…

  17. 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

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. Sustainable School Music for Poor, White, Rural Students

    ERIC Educational Resources Information Center

    Bates, Vincent C.

    2011-01-01

    "Poor white trash" is likely the most enduring and degrading in a long line of "stigmatypes"--"stigmatizing boundary terms that simultaneously denote and enact cultural and cognitive divides between in-groups and out-groups"--such as "redneck," "cracker," and "hillbilly." Some people apply these terms in reference to poor or working-class, usually…

  4. 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…

  5. 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…

  6. Mandated empowerment: handing antipoverty policy back to the poor?

    PubMed

    Banerjee, Abhijit V; Duflo, Esther

    2008-01-01

    The current trend in antipoverty policy emphasizes mandated empowerment: the poor are being handed the responsibility for making things better for themselves, largely without being asked whether this is what they want. Beneficiary control is now being built into public service delivery, while microcredit and small business promotion are seen as better ways to help the poor. The clear presumption is that the poor are both able and happy to exercise these new powers. This essay uses two examples to raise questions about these strategies. The first example is about entrepreneurship among the poor. Using data from a number of countries, we argue that there is no evidence that the median poor entrepreneur is trying his best to expand his existing businesses, even if we take into account the many constraints he faces. While many poor people own businesses, this seems to be more a survival strategy than something they want to do. The second example comes from an evaluation of a program in India that aims to involve poor rural parents in improving local public schools. The data suggest that despite being informed that they now have both the right to intervene in the school and access to funds for that purpose, and despite being made aware of how little the children were learning, parents opt to not get involved. Both examples raise concerns about committing ourselves entirely to antipoverty strategies that rely on the poor doing a lot of the work.

  7. The War against the Poor. The Underclass and Antipoverty Policy.

    ERIC Educational Resources Information Center

    Gans, Herbert J.

    For much of its history, America has been waging war against many of its poor people. Chapters 1 through 4 of this book discuss the labeling of the poor as morally inferior, which has increased in the last 15 years, blames them falsely for the ills of the American society and economy, reinforces their mistreatment, increases their misery, and…

  8. Exploring Written Narrative in Children with Poor Reading Comprehension

    ERIC Educational Resources Information Center

    Cragg, Lucy; Nation, Kate

    2006-01-01

    This study investigated written language production in 10-year-old children with impaired reading comprehension. Despite fluent and accurate reading, these children are poor at understanding what they read. Participants completed a spelling test, and were asked to write an extended narrative, prompted by a series of pictures. Poor comprehenders…

  9. 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…

  10. 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…

  11. Mitochondrial Epigenetics and Environmental Exposure.

    PubMed

    Lambertini, Luca; Byun, Hyang-Min

    2016-09-01

    The rising toll of chronic and debilitating diseases brought about by the exposure to an ever expanding number of environmental pollutants and socio-economic factors is calling for action. The understanding of the molecular mechanisms behind the effects of environmental exposures can lead to the development of biomarkers that can support the public health fields of both early diagnosis and intervention to limit the burden of environmental diseases. The study of mitochondrial epigenetics carries high hopes to provide important biomarkers of exposure and disease. Mitochondria are in fact on the frontline of the cellular response to the environment. Modifications of the epigenetic factors regulating the mitochondrial activity are emerging as informative tools that can effectively report on the effects of the environment on the phenotype. Here, we will discuss the emerging field of mitochondrial epigenetics. This review describes the main epigenetic phenomena that modify the activity of the mitochondrial DNA including DNA methylation, long and short non-coding RNAs. We will discuss the unique pattern of mitochondrial DNA methylation, describe the challenges of correctly measuring it, and report on the existing studies that have analysed the correlation between environmental exposures and mitochondrial DNA methylation. Finally, we provide a brief account of the therapeutic approaches targeting mitochondria currently under consideration.

  12. 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.

  13. Do Poor Readers Feel Angry, Sad, and Unpopular?

    PubMed Central

    Morgan, Paul L.; Farkas, George; Wu, Qiong

    2015-01-01

    We investigated whether being poorly skilled in reading contributes to children’s self-reported feelings of anger, distractibility, anxiety, sadness, loneliness, and social isolation. Data were analyzed from a longitudinal sub-sample of children (N=2,751) participating in the Early Childhood Longitudinal Study—Kindergarten Cohort. Multi-level logistic regression analyses indicated that poor readers in 3rd grade were more likely to consider themselves as angry, distractible, sad, lonely, and unpopular in 5th grade than those who had not been poor readers in 3rd grade. About 20% of 3rd grade poor readers reported feeling angry and unpopular in 5th grade. Being poorly skilled in mathematics increased children’s risk of feeling sad or lonely, but not of feeling angry, distractible, or unpopular. The results provide additional empirical evidence that reading failure contributes to generalized socio-emotional maladjustment in young children. PMID:26180489

  14. [Isocyanates: occupational exposures and disorders].

    PubMed

    Baur, X

    2003-09-01

    Isocyanates are extensively used for the production of different foams and elastomers. They also serve as glues, lacquer hardeners, inks, adhesives, fillers, finishes, sealants, coating and insulation materials. Usually, their application results in inhalative, partly also in cutaneous uptake. This review describes occupational exposures to isocyanates as well as hazardous effects. Isocyanates are used in the automotive/mechanical engineering/building and construction/mining/casting/electricity and electronic/plastics/printing/timber and furniture/white goods and textile industry, partly also in medicine. Hazardous exposures to thermal degradation products of isocyanate-based polyurethanes and other materials have also be taken into consideration. Obstructive airway diseases are the major disorder caused by isocyanates. Rare cases suffer from extrinsic allergic alveolitis or eczema. In addition to regulation-based primary prevention qualitative medical surveillance mostly prevents disorders. There is also a need for the establishment of a validated biomonitoring of endangered employees. PMID:13680473

  15. [Isocyanates: occupational exposures and disorders].

    PubMed

    Baur, X

    2003-09-01

    Isocyanates are extensively used for the production of different foams and elastomers. They also serve as glues, lacquer hardeners, inks, adhesives, fillers, finishes, sealants, coating and insulation materials. Usually, their application results in inhalative, partly also in cutaneous uptake. This review describes occupational exposures to isocyanates as well as hazardous effects. Isocyanates are used in the automotive/mechanical engineering/building and construction/mining/casting/electricity and electronic/plastics/printing/timber and furniture/white goods and textile industry, partly also in medicine. Hazardous exposures to thermal degradation products of isocyanate-based polyurethanes and other materials have also be taken into consideration. Obstructive airway diseases are the major disorder caused by isocyanates. Rare cases suffer from extrinsic allergic alveolitis or eczema. In addition to regulation-based primary prevention qualitative medical surveillance mostly prevents disorders. There is also a need for the establishment of a validated biomonitoring of endangered employees.

  16. 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 ...

  17. 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...

  18. 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...

  19. A Comparison of the Language Skills of ELLs and Monolinguals Who Are Poor Decoders, Poor Comprehenders, or Normal Readers

    ERIC Educational Resources Information Center

    Geva, Esther; Massey-Garrison, Angela

    2013-01-01

    The overall objective of this article is to examine how oral language abilities relate to reading profiles in English language learners (ELLs) and English as a first language (EL1) learners, and the extent of similarities and differences between ELLs and EL1s in three reading subgroups: normal readers, poor decoders, and poor comprehenders. The…

  20. 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…

  1. Exposure assessment for chemical and physical agents.

    PubMed

    Moretto, Angelo

    2015-01-01

    Exposure assessment to either chemical or physical agents, as applicable, is a necessary step for both etiologic diagnosis of occupational disease and health surveillance of workers. The assessment can be carried out by measurements of concentrations in air of the substance by either fixed or personal samplers. The former give an indication of the general environment, the latter, applied near the mouth of the worker, provide personalized information. Dermal exposure (deposition) and absorption occur in the occupational setting, but their measurement is so complex that there are no routine methods and no exposure limits established. Oral exposure is accidental or associated with poor hygienic practices, is very difficult to assess, and there are no occupational exposure limits of oral intake. Also accidental injuries caused by needles or other sharp objects that might be contaminated by chemicals occur but exposure assessment in this condition is almost impossible. Exposure is also assessed by biologic monitoring that entails measurements of the substance and/or of its metabolite(s) in accessible fluids, generally urine, blood, or expired air. Biochemical changes, e.g., enzyme inhibition, associated with exposure are also measured. The results of these measurements are compared with existing limit values in order to conclude on the safety of the working conditions. Since the limit values are derived with the application of conservative assumptions, there are no fine lines between health and disease. Therefore, in the clinical setting values below the limit can be generally regarded as safe. Values above the limits should be considered in conjunction with all other information to judge on the likelihood that the disease under investigation may have been caused by exposure to the substance. PMID:26563782

  2. 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…

  3. A systems view of health care for the poor.

    PubMed Central

    Prasad, N.

    1989-01-01

    A systems view is a synthesis of health policy, medical sociology, public health, and common clinical problems to describe the current crisis in health care for the poor. Medical sociology and public health are particularly relevant to understand the complexity of clinical issues. Although preventive medicine is in desuetude, it is crucial if we are to reduce the future liability of postponed medical care among the poor. Medicaid metamorphosed to Medicare, as half of its outlays are spent on care of the elderly in nursing homes. Health care for the poor will remain a moral challenge to the architects of health policy and the medical profession. PMID:2659807

  4. Poor specific antibody response immunodeficiency (dysgammaglobulinemia) predates systemic lupus erythematosus.

    PubMed

    Al Hamzi, H; Al Shaikh, A; Arnaout, R K

    2013-08-01

    Poor specific antibody response is a well-known primary immunodeficiency that is related to hypogammaglobulinemia or common variable immunodeficiency (CVID). The co-existence of CVID or hypogammaglobulinemia and systemic lupus erythematosus (SLE) has been rarely described. In all reported cases, the diagnosis of SLE antedates CVID. We report a 15-year-old Saudi girl who was diagnosed with poor specific antibody response at age 6 years in the form of poor or no antibody response and dysgammaglobulinemia. She developed SLE with musculoskeletal and hematological manifestations, positive antinuclear antibody and high anti-dsDNA nine years later. She was treated with rituximab with good response.

  5. Changes in gene expression associated with radiation exposure

    SciTech Connect

    Woloschak, G.E.; Paunesku, T.; Chang-Liu, C.M.; Grdina, D.J.

    1995-12-31

    Current research from our group has demonstrated differences in gene induction patterns for high- and low-linear energy transfer radiations; some genes are induced selectively following neutron exposure, others selectively following {gamma}-ray exposure, and others induced following exposure to either. These genes are associated with a broad array of different functions including apoptosis, cytoskeletal function, and gene regulation (dd-RT-PCR) technology to identify genes induced following exposure to different qualities of radiation and following exposure to radiation in the presence of radioprotectors.

  6. 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.

  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. PMID:27492302

  8. Low Vagal Tone Magnifies the Association Between Psychosocial Stress Exposure and Internalizing Psychopathology in Adolescents

    PubMed Central

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

    2014-01-01

    Vagal tone is a measure of cardiovascular function that facilitates adaptive responses to environmental challenge. Low vagal tone is associated with poor emotional and attentional regulation in children and has been conceptualized as a marker of sensitivity to stress. We investigated whether the associations of a wide range of psychosocial stressors with internalizing and externalizing psychopathology were magnified in adolescents with low vagal tone. Resting heart period data were collected from a diverse community sample of adolescents (ages 13–17; N =168). Adolescents completed measures assessing internalizing and externalizing psychopathology and exposure to stressors occurring in family, peer, and community contexts. Respiratory sinus arrhythmia (RSA) was calculated from the interbeat interval time series. We estimated interactions between RSA and stress exposure in predicting internalizing and externalizing symptoms and evaluated whether interactions differed by gender. Exposure to psychosocial stressors was associated strongly with psychopathology. RSA was unrelated to internalizing or externalizing problems. Significant interactions were observed between RSA and child abuse, community violence, peer victimization, and traumatic events in predicting internalizing but not externalizing symptoms. Stressors were positively associated with internalizing symptoms in adolescents with low RSA but not in those with high RSA. Similar patterns were observed for anxiety and depression. These interactions were more consistently observed for male than female individuals. Low vagal tone is associated with internalizing psychopathology in adolescents exposed to high levels of stressors. Measurement of vagal tone in clinical settings might provide useful information about sensitivity to stress in child and adolescent clients. PMID:24156380

  9. Silica gel as a particulate carrier of poorly water-soluble substances in aquatic toxicity testing.

    PubMed

    Breitholtz, Magnus; Ricklund, Niklas; Bengtsson, Bengt-Erik; Persson, N Johan

    2007-05-31

    Aquatic toxicity tests were originally developed for water-soluble substances. However, many substances are hydrophobic and thus poorly water-soluble, resulting in at least two major implications. Firstly, toxicity may not be reached within the range of water solubility of the tested compound(s), which may result in the formation of solids or droplets of the tested substance and consequently an uneven exposure. Secondly, because of multi-phase distribution of the tested substance it may be complicated to keep exposure concentrations constant. To overcome such problems, we have introduced silica gel as a particulate carrier in a toxicity test with the benthic copepod Nitocra spinipes. The main objective of the current study was to evaluate whether a controlled exposure could be achieved with the help of silica gel for testing single poorly water-soluble substances. A secondary objective was to evaluate whether an equilibrium mass balance model could predict internal concentrations that were consistent with the toxicity data and measured internal concentrations of two model hydrophobic substances, i.e., the polybrominated diphenyl ethers BDE-47 and BDE-99. Larval N. spinipes were exposed for 6 days to BDE-47 and BDE-99, respectively, in the silica gel test system and, for comparative reasons, in a similar and more traditional semi-static water test system. Via single initial amounts of the model substances administered on the silica gel, effects on both larval development and mortality resulted in higher and more concentration-related toxicity than in the water test system. We conclude that the silica gel test system enables a more controlled exposure of poorly water-soluble substances than the traditional water test system since the concentration-response relationship becomes distinct and there is no carrier solvent present during testing. Also, the single amount of added substance given in the silica gel test system limits the artefacts (e.g., increased chemical

  10. Los Angeles County Poor Farm, Patient Ward Nos. 210 & ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Los Angeles County Poor Farm, Patient Ward Nos. 210 & 211 - Type B Plan, 7601 Imperial Highway; bounded by Esperanza Street, Laurel Street, Flores Street, and Descanso Street, Downey, Los Angeles County, CA

  11. Los Angeles County Poor Farm, Patient Wards 201, 202, 203, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Los Angeles County Poor Farm, Patient Wards 201, 202, 203, 204, 205, 206, 207, 208 & 209 - Type A Plan, 7601 Imperial Highway; bounded by Esperanza Street, Hawthorn Avenue, Laurel Street, and Descanso Street, Downey, Los Angeles County, CA

  12. Poor Weight Gain in Infants and Children (Beyond the Basics)

    MedlinePlus

    ... month) – Poor quality of suck (whether breast- or bottle-fed), incorrect formula preparation; breastfeeding problems; inadequate number ... to feed him/herself (eg, by holding a bottle or eating finger foods), but may need to ...

  13. Depleting depletion: Polymer swelling in poor solvent mixtures

    NASA Astrophysics Data System (ADS)

    Mukherji, Debashish; Marques, Carlos; Stuehn, Torsten; Kremer, Kurt

    A polymer collapses in a solvent when the solvent particles dislike monomers more than the repulsion between monomers. This leads to an effective attraction between monomers, also referred to as depletion induced attraction. This attraction is the key factor behind standard polymer collapse in poor solvents. Strikingly, even if a polymer exhibits poor solvent condition in two different solvents, it can also swell in mixtures of these two poor solvents. This collapse-swelling-collapse scenario is displayed by poly(methyl methacrylate) (PMMA) in aqueous alcohol. Using molecular dynamics simulations of a thermodynamically consistent generic model and theoretical arguments, we unveil the microscopic origin of this phenomenon. Our analysis suggests that a subtle interplay of the bulk solution properties and the local depletion forces reduces depletion effects, thus dictating polymer swelling in poor solvent mixtures.

  14. Ruprecht 106 - A young metal-poor Galactic globular cluster

    SciTech Connect

    Buonanno, R.; Buscema, G.; Fusi Pecci, F.; Richer, H.B.; Fahlman, G.G. Bologna Universita British Columbia Univ., Vancouver )

    1990-12-01

    The first CCD photometric survey in the Galactic globular cluster Ruprecht 106 has been performed. The results show that Ruprecht 106 is a metal-poor cluster with (Fe/H) about -2 located at about 25 kpc from the Galactic center. A sizable, high centrally concentrated population of blue stragglers was detected. Significant differences in the positions of the turnoffs in the color-magnitude diagram are found compared to those in metal-poor clusters. The cluster appears younger than other typical metal-poor Galactic globulars by about 4-5 Gyr; if true, this object would represent the first direct proof of the existence of a significant age spread among old, very metal-poor clusters. 51 refs.

  15. Many Hispanics, Poor Still Without Health Insurance: Report

    MedlinePlus

    ... fullstory_160507.html Many Hispanics, Poor Still Without Health Insurance: Report Majority live in states that haven't ... 2016 (HealthDay News) -- Despite an overall rise in health insurance coverage among all Americans, Hispanics, low-income earners ...

  16. Poor Sleep May Worsen Thinking Problems in MS Patients

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159463.html Poor Sleep May Worsen Thinking Problems in MS Patients Study found link between severity of sleep apnea and performance on attention, memory tests To ...

  17. Exploring the early Universe with extremely metal-poor stars

    NASA Astrophysics Data System (ADS)

    Hansen, Terese T.; Christlieb, Norbert; Hansen, Camilla J.; Beers, Timothy C.

    2016-08-01

    The earliest phases of Galactical chemical evolution and nucleosynthesis can be investigated by studying the old metal-poor stars. It has been recognized that a large fraction of metal-poor stars possess significant over-abundances of carbon relative to iron. Here we present the results of a 23-star homogeneously analyzed sample of metal-poor candidates from the Hamburg/ESO survey. We have derived abundances for a large number of elements ranging from Li to Pb. The sample includes four ultra metal-poor stars ([Fe/H] < -4.0), six CEMP-no stars, five CEMP-s stars, two CEMP-r stars and two CEMP-r/s stars. This broad variety of the sample stars gives us an unique opportunity to explore different abundance patterns at low metallicity.

  18. [Poorly healing periorbital wounds. Therapeutic use of maggots].

    PubMed

    Pitz, S; Renieri, G; Gericke, A

    2012-05-01

    The treatment of poorly healing wounds, although not a typical problem in the periorbital area, has been enriched by the option of biosurgery, the therapeutic application of larvae of the blow fly (Lucilia sericata).

  19. Regulating the introduction of new chemicals under section 5 of TSCA: improving the efficiency of the process and reducing potential injury in the workplace through the use of operational MSDS and exposure limits.

    PubMed

    Rosenthal, I; Jayjock, M A; Keener, R L; Plamondon, J E

    1991-10-01

    The Toxic Substances Control Act (TSCA) authorizes the EPA to take appropriate actions to ensure that new and existing chemicals do not pose "unreasonable risk" to health or the environment. Section 2(b)(3) of the Act directs the Agency to accomplish this objective in a manner that does "not impede unduly or create unnecessary economic barriers to technological innovation." In recent years, critics have felt that the EPA has failed to achieve these primary goals of TSCA. This paper considers some of the reasons for this criticism and advocates an alternate approach of exposure limits and operationally sufficient controls to assist in achieving these goals. An illustration of how this alternate approach might work under practical conditions is presented, using as an example a new chemical substance from the class of acrylate monomers. These concepts and risk assessments provide data for a better design of future studies according to good laboratory practice and quality assurance. PMID:1669965

  20. Chronic ethanol exposure combined with high fat diet up-regulates P2X7 receptors that parallels neuroinflammation and neuronal loss in C57BL/6J mice.

    PubMed

    Asatryan, Liana; Khoja, Sheraz; Rodgers, Kathleen E; Alkana, Ronald L; Tsukamoto, Hidekazu; Davies, Daryl L

    2015-08-15

    The present investigation tested the role of ATP-activated P2X7 receptors (P2X7Rs) in alcohol-induced brain damage using a model that combines intragastric (iG) ethanol feeding and high fat diet in C57BL/6J mice (Hybrid). The Hybrid paradigm caused increased levels of pro-inflammatory markers, changes in microglia and astrocytes, reduced levels of neuronal marker NeuN and increased P2X7R expression in ethanol-sensitive brain regions. Observed changes in P2X7R and NeuN expression were more pronounced in Hybrid paradigm with inclusion of additional weekly binges. In addition, high fat diet during Hybrid exposure aggravated the increase in P2X7R expression and activation of glial cells.

  1. Chronic ethanol exposure combined with high fat diet up-regulates P2X7 receptors that parallels neuroinflammation and neuronal loss in C57BL/6J mice.

    PubMed

    Asatryan, Liana; Khoja, Sheraz; Rodgers, Kathleen E; Alkana, Ronald L; Tsukamoto, Hidekazu; Davies, Daryl L

    2015-08-15

    The present investigation tested the role of ATP-activated P2X7 receptors (P2X7Rs) in alcohol-induced brain damage using a model that combines intragastric (iG) ethanol feeding and high fat diet in C57BL/6J mice (Hybrid). The Hybrid paradigm caused increased levels of pro-inflammatory markers, changes in microglia and astrocytes, reduced levels of neuronal marker NeuN and increased P2X7R expression in ethanol-sensitive brain regions. Observed changes in P2X7R and NeuN expression were more pronounced in Hybrid paradigm with inclusion of additional weekly binges. In addition, high fat diet during Hybrid exposure aggravated the increase in P2X7R expression and activation of glial cells. PMID:26198936

  2. Chronic ethanol exposure combined with high fat diet up-regulates P2X7 receptors that parallels neuroinflammation and neuronal loss in C57BL/6J mice

    PubMed Central

    Asatryan, Liana; Khoja, Sheraz; Rodgers, Kathleen E; Alkana, Ronald L; Tsukamoto, Hidekatsu; Davies, Daryl L.

    2015-01-01

    The present investigation tested the role of ATP-activated P2X7 receptors (P2X7Rs) in alcohol-induced brain damage using a model that combines intragastric (iG) ethanol feeding and high fat diet in C57BL/6J mice (Hybrid). The Hybrid paradigm caused increased levels of pro-inflammatory markers, changes in microglia and astrocytes, reduced levels of neuronal marker NeuN and increased P2X7R expression in ethanol-sensitive brain regions. Observed changes in P2X7R and NeuN expression were more pronounced in Hybrid paradigm with inclusion of additional weekly binges. In addition, high fat diet during Hybrid exposure aggravated the increase in P2X7R expression and activation of glial cells. PMID:26198936

  3. Exposures to lead.

    PubMed

    Callan, Anna C; Hinwood, Andrea L

    2011-01-01

    The Pacific Basin Consortium for Environment and Health hosted a workshop on Exposures to Lead. Speakers from Australia and the United States of America addressed current research knowledge on lead exposures and health effects in children, risk assessment and communication issues in dealing with lead exposure sources, different methods for assessing exposure, and the variety of scenarios where lead still remains a pollutant of concern. Mining continues to be a source of lead for many communities, and approaches to reducing exposures in these settings present particular challenges. A Perth Declaration for the Global Reduction of Childhood Lead Exposure was signed by participants of the meeting and is aimed at increasing attention to the need to continue to assess lead in the environment and to develop strategies to reduce lead in the environment and exposure by communities. PMID:21714377

  4. Exposures to lead.

    PubMed

    Callan, Anna C; Hinwood, Andrea L

    2011-01-01

    The Pacific Basin Consortium for Environment and Health hosted a workshop on Exposures to Lead. Speakers from Australia and the United States of America addressed current research knowledge on lead exposures and health effects in children, risk assessment and communication issues in dealing with lead exposure sources, different methods for assessing exposure, and the variety of scenarios where lead still remains a pollutant of concern. Mining continues to be a source of lead for many communities, and approaches to reducing exposures in these settings present particular challenges. A Perth Declaration for the Global Reduction of Childhood Lead Exposure was signed by participants of the meeting and is aimed at increasing attention to the need to continue to assess lead in the environment and to develop strategies to reduce lead in the environment and exposure by communities.

  5. Population Density, Poor Sanitation, and Enteric Infections in Nueva Santa Rosa, Guatemala

    PubMed Central

    Jarquin, Claudia; Arnold, Benjamin F.; Muñoz, Fredy; Lopez, Beatriz; Cuéllar, Victoria M.; Thornton, Andrew; Patel, Jaymin; Reyes, Lisette; Roy, Sharon L.; Bryan, Joe P.; McCracken, John P.; Colford, John M.

    2016-01-01

    Poor sanitation could pose greater risk for enteric pathogen transmission at higher human population densities because of greater potential for pathogens to infect new hosts through environmentally mediated and person-to-person transmission. We hypothesized that incidence and prevalence of diarrhea, enteric protozoans, and soil-transmitted helminth infections would be higher in high-population-density areas compared with low-population-density areas, and that poor sanitation would pose greater risk for these enteric infections at high density compared with low density. We tested our hypotheses using 6 years of clinic-based diarrhea surveillance (2007–2013) including 4,360 geolocated diarrhea cases tested for 13 pathogens and a 2010 cross-sectional survey that measured environmental exposures from 204 households (920 people) and tested 701 stool specimens for enteric parasites. We found that population density was not a key determinant of enteric infection nor a strong effect modifier of risk posed by poor household sanitation in this setting. PMID:26856919

  6. Economic stress in childhood and adulthood, and poor psychological health: three life course hypotheses.

    PubMed

    Lindström, Martin; Fridh, Maria; Rosvall, Maria

    2014-02-28

    Investigations of mental health in a life course perspective are scarce. The aim is to investigate associations between economic stress in childhood and adulthood, and poor psychological health in adulthood with reference to the accumulation, critical period and social mobility hypotheses in life course epidemiology. The 2008 public health survey in Skåne is a cross-sectional postal questionnaire study. A random sample was invited which yielded 28,198 respondents aged 18-80 (55% participation). Psychological health was assessed with the GHQ12 instrument. Logistic regression models were used to investigate the associations adjusting for age, country of birth, socioeconomic status, emotional support, instrumental support and trust, and stratifying by sex. The accumulation hypothesis was confirmed because combined childhood and adulthood exposures to economic stress were associated with poor psychological health in a graded manner. The social mobility hypothesis was also confirmed. The critical period hypothesis was not confirmed because both childhood and adulthood economic stress remained significantly associated with poor psychological health in adulthood. Economic stress in childhood is associated with mental health in adulthood.

  7. Population Density, Poor Sanitation, and Enteric Infections in Nueva Santa Rosa, Guatemala.

    PubMed

    Jarquin, Claudia; Arnold, Benjamin F; Muñoz, Fredy; Lopez, Beatriz; Cuéllar, Victoria M; Thornton, Andrew; Patel, Jaymin; Reyes, Lisette; Roy, Sharon L; Bryan, Joe P; McCracken, John P; Colford, John M

    2016-04-01

    Poor sanitation could pose greater risk for enteric pathogen transmission at higher human population densities because of greater potential for pathogens to infect new hosts through environmentally mediated and person-to-person transmission. We hypothesized that incidence and prevalence of diarrhea, enteric protozoans, and soil-transmitted helminth infections would be higher in high-population-density areas compared with low-population-density areas, and that poor sanitation would pose greater risk for these enteric infections at high density compared with low density. We tested our hypotheses using 6 years of clinic-based diarrhea surveillance (2007-2013) including 4,360 geolocated diarrhea cases tested for 13 pathogens and a 2010 cross-sectional survey that measured environmental exposures from 204 households (920 people) and tested 701 stool specimens for enteric parasites. We found that population density was not a key determinant of enteric infection nor a strong effect modifier of risk posed by poor household sanitation in this setting. PMID:26856919

  8. Population Density, Poor Sanitation, and Enteric Infections in Nueva Santa Rosa, Guatemala.

    PubMed

    Jarquin, Claudia; Arnold, Benjamin F; Muñoz, Fredy; Lopez, Beatriz; Cuéllar, Victoria M; Thornton, Andrew; Patel, Jaymin; Reyes, Lisette; Roy, Sharon L; Bryan, Joe P; McCracken, John P; Colford, John M

    2016-04-01

    Poor sanitation could pose greater risk for enteric pathogen transmission at higher human population densities because of greater potential for pathogens to infect new hosts through environmentally mediated and person-to-person transmission. We hypothesized that incidence and prevalence of diarrhea, enteric protozoans, and soil-transmitted helminth infections would be higher in high-population-density areas compared with low-population-density areas, and that poor sanitation would pose greater risk for these enteric infections at high density compared with low density. We tested our hypotheses using 6 years of clinic-based diarrhea surveillance (2007-2013) including 4,360 geolocated diarrhea cases tested for 13 pathogens and a 2010 cross-sectional survey that measured environmental exposures from 204 households (920 people) and tested 701 stool specimens for enteric parasites. We found that population density was not a key determinant of enteric infection nor a strong effect modifier of risk posed by poor household sanitation in this setting.

  9. The Cek1‑mediated MAP kinase pathway regulates exposure of α‑1,2 and β‑1,2‑mannosides in the cell wall of Candida albicans modulating immune recognition.

    PubMed

    Román, E; Correia, I; Salazin, A; Fradin, C; Jouault, T; Poulain, D; Liu, F-T; Pla, J

    2016-07-01

    The Cek1 MAP kinase (MAPK) mediates vegetative growth and cell wall biogenesis in the fungal pathogen Candida albicans. Alterations in the fungal cell wall caused by a defective Cek1‑mediated signaling pathway leads to increased β‑1,3‑glucan exposure influencing dectin‑1 fungal recognition by immune cells. We show here that cek1 cells also display an increased exposure of α‑1,2 and β‑1,2‑mannosides (α‑M and β‑M), a phenotype shared by strains defective in the activating MAPKK Hst7, suggesting a general defect in cell wall assembly. cek1 cells display walls with loosely bound material as revealed by transmission electron microscopy and are sensitive to tunicamycin, an inhibitor of N‑glycosylation. Transcriptomal analysis of tunicamycin treated cells revealed a differential pattern between cek1 and wild type cells which involved mainly cell wall and stress related genes. Mapping α‑M and β‑M epitopes in the mannoproteins of different cell wall fractions (CWMP) revealed an important shift in the molecular weight of the mannan derived from mutants defective in this MAPK pathway. We have also assessed the role of galectin‑3, a member of a β‑galactoside‑binding protein family shown to bind to and kill C. albicans through β‑M recognition, in the infection caused by cek1 mutants. Increased binding of cek1 to murine macrophages was shown to be partially blocked by lactose. Galectin-3(-/-) mice showed increased resistance to fungal infection, although galectin-3 did not account for the reduced virulence of cek1 mutants in a mouse model of systemic infection. All these data support a role for the Cek1‑mediated pathway in fungal cell wall maintenance, virulence and antifungal discovery.

  10. Sound exposure during outdoor music festivals.

    PubMed

    Tronstad, Tron V; Gelderblom, Femke B

    2016-01-01

    Most countries have guidelines to regulate sound exposure at concerts and music festivals. These guidelines limit the allowed sound pressure levels and the concert/festival's duration. In Norway, where there is such a guideline, it is up to the local authorities to impose the regulations. The need to prevent hearing-loss among festival participants is self-explanatory, but knowledge of the actual dose received by visitors is extremely scarce. This study looks at two Norwegian music festivals where only one was regulated by the Norwegian guideline for concert and music festivals. At each festival the sound exposure of four participants was monitored with noise dose meters. This study compared the exposures experienced at the two festivals, and tested them against the Norwegian guideline and the World Health Organization's recommendations. Sound levels during the concerts were higher at the festival not regulated by any guideline, and levels there exceeded both the national and the Worlds Health Organization's recommendations. The results also show that front-of-house measurements reliably predict participant exposure. PMID:27569410

  11. 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...

  12. Explaining the Role of Proximate Determinants on Fertility Decline among Poor and Non-Poor in Asian Countries

    PubMed Central

    Majumder, Nabanita; Ram, Faujdar

    2015-01-01

    Objectives We examined the overall contributions of the poor and non-poor in fertility decline across the Asian countries. Further, we analyzed the direct and indirect factors that determine the reproductive behaviour of two distinct population sub-groups. Design Data from several new rounds of DHS surveys are available over the past few years. The DHS provides cross-nationally comparable and useful data on fertility, family planning, maternal and child health along with the other information. Six selected Asian countries namely: Bangladesh, India, Indonesia, Nepal, Philippines, and Vietnam are considered for the purpose of the study. Three rounds of DHS surveys for each country (except Vietnam) are considered in the present study. Methods Economic status is measured by computing a “wealth index”, i.e. a composite indicator constructed by aggregating data on asset ownership and housing characteristics using principal components analysis (PCA). Computed household wealth index has been broken into three equal parts (33.3 percent each) and the lowest and the highest 33.3 percent is considered as poor and non-poor respectively. The Bongaarts model was employed to quantify the contribution of each of the proximate determinants of fertility among poor and non-poor women. Results Fertility reduction across all population subgroups is now an established fact despite the diversity in the level of socio-economic development in Asian countries. It is clear from the analysis that fertility has declined irrespective of economic status at varying degrees within and across the countries which can be attributed to the increasing level of contraceptive use especially among poor women. Over the period of time changing marriage pattern and induced abortion are playing an important role in reducing fertility among poor women. Conclusions Fertility decline among majority of the poor women across the Asian countries is accompanied by high prevalence of contraceptive use followed by

  13. Physical properties of luminous dust-poor quasars

    SciTech Connect

    Jun, Hyunsung David; Im, Myungshin E-mail: mim@astro.snu.ac.kr

    2013-12-20

    We identify and characterize a population of luminous, dust-poor quasars at 0 < z < 5 that is photometrically similar to objects previously found at z > 6. This class of active galactic nuclei is known to show little IR emission from dusty structure, but it is poorly understood in terms of number evolution and dependence on physical quantities. To better understand the properties of these quasars, we compile a rest-frame UV to IR library of 41,000 optically selected type 1 quasars with L {sub bol} > 10{sup 45.7} erg s{sup –1}. After fitting the broadband spectral energy distributions (SEDs) with accretion disk and dust components, we find 0.6% of our sample to be hot dust-poor, with rest-frame 2.3 μm to 0.51 μm flux density ratios of –0.5 dex or less. The dust-poor SEDs are blue in the UV-optical and weak in the mid-IR, such that their accretion disks are less obscured and the hot dust emission traces that of warm dust down to the dust-poor regime. At a given bolometric luminosity, dust-poor quasars are lower in black hole mass and higher in Eddington ratio than general luminous quasars, suggesting that they are in a rapidly growing evolutionary state in which the dust-poor phase appears as a short or rare phenomenon. The dust-poor fraction increases with redshift, and possible implications for their evolution are discussed.

  14. Imaging features of poorly controlled congenital adrenal hyperplasia in adults

    PubMed Central

    Sherlock, M; Healy, N A; Doody, O; Govender, P; Torreggiani, W C

    2015-01-01

    Congenital adrenal hyperplasia (CAH) is a genetic autosomal recessive condition most frequently as a result of a mutation in the 21-hydroxylase enzyme gene. Patients with poorly controlled CAH can manifest characteristic imaging findings as a result of adrenocorticotrophic hormone stimulation or the effects of cortisol precursor excess on various target organs. We present a spectrum of imaging findings encountered in adult patients with poorly treated CAH, with an emphasis on radiological features and their clinical relevance. PMID:26133223

  15. Effects of Developmental Lead Exposure on the Hippocampal Transcriptome: Influences of Sex, Developmental Period, and Lead Exposure Level

    PubMed Central

    Schneider, Jay S

    2012-01-01

    Developmental lead (Pb) exposure has profound effects on cognition and behavior. Much is known about effects of Pb on hippocampal-mediated behaviors, but little is known about the molecular consequences of Pb exposure and the influences of developmental timing of exposure, level of exposure, and sex as effect modifiers of Pb exposure on the brain. The aim of this study was to examine the effects of different levels of Pb exposure (250 and 750 ppm Pb acetate) during perinatal (gestation/lactation) and postnatal (through postnatal day 45) periods on the hippocampal transcriptome in male and female Long Evans rats. Total RNA was extracted from hippocampus from four animals per experimental condition. RNA was hybridized to Affymetrix Rat Gene RNA Arrays using standard methods. Pb exposure per se influenced the expression of 717 transcripts (328 unique annotated genes), with many influenced in a sex-independent manner. Significant differences in gene expression patterns were also influenced by timing and level of exposure, with generally larger effects at the lower level of exposure across all groups. Statistically enriched biological functions included ion binding, regulation of RNA metabolic processes, and positive regulation of macromolecule biosynthetic processes. Processes of regulation of transcription and regulation of gene expression were preferentially enriched in males, regardless of timing or amount of Pb exposure. The effect on transcription factors and the diverse pathways or networks affected by Pb suggest a substantial effect of developmental Pb exposure on plasticity and adaptability, with these effects significantly modified by sex, developmental window of exposure, and level of Pb exposure. PMID:22641619

  16. Does overgeneral autobiographical memory result from poor memory for task instructions?

    PubMed

    Yanes, Paula K; Roberts, John E; Carlos, Erica L

    2008-10-01

    Considerable previous research has shown that retrieval of overgeneral autobiographical memories (OGM) is elevated among individuals suffering from various emotional disorders and those with a history of trauma. Although previous theories suggest that OGM serves the function of regulating acute negative affect, it is also possible that OGM results from difficulties in keeping the instruction set for the Autobiographical Memory Test (AMT) in working memory, or what has been coined "secondary goal neglect" (Dalgleish, 2004). The present study tested whether OGM is associated with poor memory for the task's instruction set, and whether an instruction set reminder would improve memory specificity over repeated trials. Multilevel modelling data-analytic techniques demonstrated a significant relationship between poor recall of instruction set and probability of retrieving OGMs. Providing an instruction set reminder for the AMT relative to a control task's instruction set improved memory specificity immediately afterward.

  17. Clinicopathological significance of gastric poorly differentiated medullary carcinoma.

    PubMed

    Hirai, Hideaki; Yoshizawa, Tadashi; Morohashi, Satoko; Haga, Toshihiro; Wu, Yunyan; Ota, Rie; Takatsuna, Masafumi; Akasaka, Harue; Hakamada, Kenichi; Kijima, Hiroshi

    2016-01-01

    Poorly differentiated gastric adenocarcinoma of solid type is known to show a clinicopathological diversity, but its morphological characteristics have rarely been investigated. In this study, we defined poorly differentiated medullary carcinoma indicating the following three characteristics: (i) more than 90% of the entire tumor were composed of poorly differentiated adenocarcinoma in a medullary growth, (ii) the tumor exhibited an expansive growth at the tumor margin, and (iii) special types such as an α-fetoprotein-producing carcinoma, neuroendocrine carcinoma, and carcinoma with lymphoid stroma were excluded. Based on the definition, we subclassified the poorly differentiated gastric adenocarcinoma of solid type into the two groups: medullary carcinoma and non-medullary carcinoma, and clinicopathologically analyzed 23 cases of medullary carcinomas and 38 cases of non-medullary carcinomas. The medullary carcinomas less frequently displayed lymphatic invasion, venous invasion, and lymph node metastasis, compared with the non-medullary carcinoma (P < 0.001, P = 0.002, and P < 0.001, respectively). The patients with medullary carcinomas significantly showed better disease-free survival (P = 0.017). This is the first study to demonstrate that poorly differentiated adenocarcinoma of solid type can be subclassified into tumors with low and high malignant potentials. Gastric poorly differentiated medullary carcinoma is considered to be a novel histological type predicting good patients' prognosis. PMID:27108877

  18. Poor Mental Health and Reduced Decline in Smoking Prevalence

    PubMed Central

    Steinberg, Marc L.; Williams, Jill M.; Li, Yunqing

    2015-01-01

    Introduction Although smoking prevalence has been declining for smokers without mental illness, it has been static for those with mental illness. The purpose of this study is to examine differences in smoking rates and trajectories of smoking prevalence in the often-overlooked population of smokers with poor mental health, compared with those with better mental health. Methods Data were obtained from the Behavioral Risk Factor Surveillance System from 2001 to 2010 to examine the relationship between poor mental health and current, daily, and intermittent tobacco use in New Jersey. Data were analyzed in 2014. Results During 2001–2010, current, daily, and intermittent smoking prevalence was higher in participants with poor mental health than those with better mental health. In addition, with the exception of 2 years, prevalence rates remained unchanged in this 10-year period for those with poor mental health while they significantly decreased for those with better mental health. Conclusions The disparity in which smokers with poor mental health are more likely to be current smokers and less likely to be never smokers as compared with those with better mental health has increased over time. These data suggest the need to more closely examine tobacco control and treatment policies in smokers with behavioral health issues. It is possible that tobacco control strategies are not reaching those with poor mental health, or, if they are, their messages are not translating into successful cessation. PMID:26071864

  19. Kinematics and dynamics of the Morgan poor clusters

    NASA Astrophysics Data System (ADS)

    Bird, Christina M.; Beers, Timothy C.; Kriessler, Jeffrey R.; Huchra, John P.

    1995-07-01

    Eighteen of the 23 MKW and AWM poor clusters now have 10 or more measured redshifts within 1.5h-1 Mpc of the central galaxy; 11 clusters have at least 20 measured redshifts. Based on the 21 clusters for which we have sufficient velocity information, the median velocity scale is 336 km s-1, a factor of two smaller than found for rich clusters. Several of the poor clusters exhibit complex velocity distributions due to the presence of nearby clumps of galaxies. We check on the velocity of the dominant galaxy in each poor cluster relative to the remaining cluster members. Significantly high relative velocities of the dominant galaxy are found in only 4 of 21 poor clusters, 3 of which we suspect are due to contamination of the parent velocity distribution. Several statistical tests indicate that the D/cD galaxies are at the kinematic centers of the parent poor cluster velocity distributions. Mass-to-light ratios for the 13 of the 15 poor clusters for which we have the required data are in the range 50<=M/LB(0)<=200 Msolar/Lsolar.

  20. HAT3-mediated acetylation of PCNA precedes PCNA monoubiquitination following exposure to UV radiation in Leishmania donovani.

    PubMed

    Kumar, Devanand; Saha, Swati

    2015-06-23

    Histone modifications impact various processes. In examining histone acetyltranferase HAT3 of Leishmania donovani, we find elimination of HAT3 causes decreased cell viability due to defects in histone deposition, and aberrant cell cycle progression pattern. HAT3 associates with proliferating cell nuclear antigen (PCNA), helping load PCNA onto chromatin in proliferating cells. HAT3-nulls show heightened sensitivity to UV radiation. Following UV exposure, PCNA cycles off/on chromatin only in cells expressing HAT3. Inhibition of the ubiquitin-proteasome pathway prior to UV exposure allows accumulation of chromatin-bound PCNA, and reveals that HAT3-nulls are deficient in PCNA monoubiquitination as well as polyubiquitination. While poor monoubiquitination of PCNA may adversely affect translesion DNA synthesis-based repair processes, polyubiquitination deficiencies may result in continued retention of chromatin-bound PCNA, leading to genomic instability. On suppressing the proteasome pathway we also find that HAT3 mediates PCNA acetylation in response to UV. HAT3-mediated PCNA acetylation may serve as a flag for PCNA ubiquitination, thus aiding DNA repair. While PCNA acetylation has previously been linked to its degradation following UV exposure, this is the first report linking a HAT-mediated PCNA acetylation to PCNA monoubiquitination. These findings add a new dimension to our knowledge of the mechanisms regulating PCNA ubiquitination post-UV exposure in eukaryotes.