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Sample records for pathways linking socioeconomic

  1. Neurobiological Pathways Linking Socioeconomic Position and Health

    PubMed Central

    Gianaros, Peter J.; Manuck, Stephen B.

    2010-01-01

    Across individuals, risk for poor health varies inversely with socioeconomic position (SEP). The pathways by which SEP affects health have been viewed from many epidemiological perspectives. Central to these perspectives is the notion that socioeconomic health disparities arise from an interplay between nested, recursive, and cumulative environmental, social, familial, psychological, behavioral, and physiological processes that unfold over the life span. Epidemiological perspectives on socioeconomic health disparities, however, have not yet formally integrated emerging findings from neuropharmacological, molecular genetic, and neuroimaging studies demonstrating that indicators of SEP relate to patterns of brain neurotransmission, brain morphology, and brain functionality implicated in the etiology of chronic medical conditions and psychological disorders. Here, we survey these emerging findings and consider how future neurobiological studies in this area can enhance our understanding of the pathways by which different dimensions of SEP become embodied by the brain to influence health throughout life. PMID:20498294

  2. Psychological Perspectives on Pathways Linking Socioeconomic Status and Physical Health

    PubMed Central

    Matthews, Karen A.; Gallo, Linda C.

    2011-01-01

    Low socioeconomic status (SES) is a reliable correlate of poor physical health. Rather than treat SES as a covariate, health psychology has increasingly focused on the psychobiological pathways that inform understanding why SES is related to physical health. This review assesses the status of research that has examined stress and its associated distress, and social and personal resources as pathways. It highlights work on biomarkers and biological pathways related to SES that can serve as intermediate outcomes in future studies. Recent emphasis on the accumulation of psychobiological risks across the life course is summarized and represents an important direction for future research. Studies that test pathways from SES to candidate psychosocial pathways to health outcomes are few in number but promising. Future research should test integrated models rather than taking piecemeal approaches to evidence. Much work remains to be done, but the questions are of great health significance. PMID:20636127

  3. Inflammatory Pathways Link Socioeconomic Inequalities to White Matter Architecture

    PubMed Central

    Gianaros, Peter J.; Marsland, Anna L.; Sheu, Lei K.; Erickson, Kirk I.; Verstynen, Timothy D.

    2013-01-01

    Socioeconomic disadvantage confers risk for aspects of ill health that may be mediated by systemic inflammatory influences on the integrity of distributed brain networks. Following this hypothesis, we tested whether socioeconomic disadvantage related to the structural integrity of white matter tracts connecting brain regions of distributed networks, and whether such a relationship would be mediated by anthropometric, behavioral, and molecular risk factors associated with systemic inflammation. Otherwise healthy adults (N= 155, aged 30–50 years, 78 men) completed protocols assessing multilevel indicators of socioeconomic position (SEP), anthropometric and behavioral measures of adiposity and cigarette smoking, circulating levels of C-reactive protein (CRP), and white matter integrity by diffusion tensor imaging. Mediation modeling was used to test associations between SEP indicators and measures of white matter tract integrity, as well as indirect mediating paths. Measures of tract integrity followed a socioeconomic gradient: individuals completing more schooling, earning higher incomes, and residing in advantaged neighborhoods exhibited increases in white matter fractional anisotropy and decreases in radial diffusivity, relative to disadvantaged individuals. Moreover, analysis of indirect paths showed that adiposity, cigarette smoking, and CRP partially mediated these effects. Socioeconomic inequalities may relate to diverse health disparities via inflammatory pathways impacting the structural integrity of brain networks. PMID:22772650

  4. Inflammatory pathways link socioeconomic inequalities to white matter architecture.

    PubMed

    Gianaros, Peter J; Marsland, Anna L; Sheu, Lei K; Erickson, Kirk I; Verstynen, Timothy D

    2013-09-01

    Socioeconomic disadvantage confers risk for aspects of ill health that may be mediated by systemic inflammatory influences on the integrity of distributed brain networks. Following this hypothesis, we tested whether socioeconomic disadvantage related to the structural integrity of white matter tracts connecting brain regions of distributed networks, and whether such a relationship would be mediated by anthropometric, behavioral, and molecular risk factors associated with systemic inflammation. Otherwise healthy adults (N= 155, aged 30-50 years, 78 men) completed protocols assessing multilevel indicators of socioeconomic position (SEP), anthropometric and behavioral measures of adiposity and cigarette smoking, circulating levels of C-reactive protein (CRP), and white matter integrity by diffusion tensor imaging. Mediation modeling was used to test associations between SEP indicators and measures of white matter tract integrity, as well as indirect mediating paths. Measures of tract integrity followed a socioeconomic gradient: individuals completing more schooling, earning higher incomes, and residing in advantaged neighborhoods exhibited increases in white matter fractional anisotropy and decreases in radial diffusivity, relative to disadvantaged individuals. Moreover, analysis of indirect paths showed that adiposity, cigarette smoking, and CRP partially mediated these effects. Socioeconomic inequalities may relate to diverse health disparities via inflammatory pathways impacting the structural integrity of brain networks. PMID:22772650

  5. Ethnic Variations of Pathways Linking Socioeconomic Status, Parenting, and Preacademic Skills in a Nationally Representative Sample

    ERIC Educational Resources Information Center

    Iruka, Iheoma U.; Dotterer, Aryn M.; Pungello, Elizabeth P.

    2014-01-01

    Research Findings: Grounded in the investment model and informed by the integrative theory of the study of minority children, this study used the Early Childhood Longitudinal Study-Birth Cohort data set, a nationally representative sample of young children, to investigate whether the association between socioeconomic status (family income and…

  6. Life Course Pathways of Adversities Linking Adolescent Socioeconomic Circumstances and Functional Somatic Symptoms in Mid-Adulthood: A Path Analysis Study

    PubMed Central

    Jonsson, Frida; San Sebastian, Miguel; Strömsten, Lotta M. J.; Hammarström, Anne; Gustafsson, Per E.

    2016-01-01

    While research examining the health impact of early socioeconomic conditions suggests that effects may exist independently of or jointly with adult socioeconomic position, studies exploring other potential pathways are few. Following a chain of risk life course model, this prospective study seeks to examine whether pathways of occupational class as well as material and social adversities across the life course link socioeconomic disadvantage in adolescent to functional somatic symptoms in mid-adulthood. Applying path analysis, a multiple mediator model was assessed using prospective data collected during 26 years through the Northern Swedish Cohort. The sample contained 987 individuals residing in the municipality of Luleå, Sweden, who participated in questionnaire surveys at age 16, 21, 30 and 42. Socioeconomic conditions (high/low) in adolescence (age 16) were operationalized using the occupation of the parents, while occupational class in adulthood (manual/non-manual) was measured using the participant’s own occupation at age 21 and 30. The adversity measurements were constructed as separate age specific parcels at age 21 and 30. Social adversity included items pertaining to stressful life events that could potentially harm salient relationships, while material adversity was operationalized using items concerning unfavorable financial and material circumstances. Functional somatic symptoms at age 42 was a summary measure of self-reported physical symptoms, palpitation and sleeping difficulties that had occurred during the last 12 months. An association between socioeconomic conditions at age 16 and functional somatic symptoms at age 42 (r = 0.068) which was partially explained by people’s own occupational class at age 21 and then material as well as social adversity at age 30 was revealed. Rather than proposing a direct and independent health effect of the socioeconomic conditions of the family, the present study suggests that growing up in an unfavorable

  7. Forecasting civil conflict along the shared socioeconomic pathways

    NASA Astrophysics Data System (ADS)

    Hegre, Håvard; Buhaug, Halvard; Calvin, Katherine V.; Nordkvelle, Jonas; Waldhoff, Stephanie T.; Gilmore, Elisabeth

    2016-05-01

    Climate change and armed civil conflict are both linked to socioeconomic development, although conditions that facilitate peace may not necessarily facilitate mitigation and adaptation to climate change. While economic growth lowers the risk of conflict, it is generally associated with increased greenhouse gas emissions and costs of climate mitigation policies. This study investigates the links between growth, climate change, and conflict by simulating future civil conflict using new scenario data for five alternative socioeconomic pathways with different mitigation and adaptation assumptions, known as the shared socioeconomic pathways (SSPs). We develop a statistical model of the historical effect of key socioeconomic variables on country-specific conflict incidence, 1960-2013. We then forecast the annual incidence of conflict, 2014-2100, along the five SSPs. We find that SSPs with high investments in broad societal development are associated with the largest reduction in conflict risk. This is most pronounced for the least developed countries—poverty alleviation and human capital investments in poor countries are much more effective instruments to attain global peace and stability than further improvements to wealthier economies. Moreover, the SSP that describes a sustainability pathway, which poses the lowest climate change challenges, is as conducive to global peace as the conventional development pathway.

  8. Forecasting civil conflict along the shared socioeconomic pathways

    NASA Astrophysics Data System (ADS)

    Hegre, Håvard; Buhaug, Halvard; Calvin, Katherine V.; Nordkvelle, Jonas; Waldhoff, Stephanie T.; Gilmore, Elisabeth

    2016-05-01

    Climate change and armed civil conflict are both linked to socioeconomic development, although conditions that facilitate peace may not necessarily facilitate mitigation and adaptation to climate change. While economic growth lowers the risk of conflict, it is generally associated with increased greenhouse gas emissions and costs of climate mitigation policies. This study investigates the links between growth, climate change, and conflict by simulating future civil conflict using new scenario data for five alternative socioeconomic pathways with different mitigation and adaptation assumptions, known as the shared socioeconomic pathways (SSPs). We develop a statistical model of the historical effect of key socioeconomic variables on country-specific conflict incidence, 1960–2013. We then forecast the annual incidence of conflict, 2014–2100, along the five SSPs. We find that SSPs with high investments in broad societal development are associated with the largest reduction in conflict risk. This is most pronounced for the least developed countries—poverty alleviation and human capital investments in poor countries are much more effective instruments to attain global peace and stability than further improvements to wealthier economies. Moreover, the SSP that describes a sustainability pathway, which poses the lowest climate change challenges, is as conducive to global peace as the conventional development pathway.

  9. The need for and use of socio-economic scenarios for climate change analysis: A new approach based on shared socio-economic pathways

    SciTech Connect

    Kriegler, Elmar; O'Neill, Brian; Hallegatte, Stephane; Kram, Tom; Lempert, Rob; Moss, Richard H.; Wilbanks, Thomas

    2012-10-01

    A new set of socioeconomic scenarios (Shared Socioeconomic Pathways) are described that provide a set of global narratives and socio-economic pathways to pair with climate model scenarios developed using the new Representative Concentration Pathways.

  10. How does childhood socioeconomic hardship affect reproductive strategy? Pathways of development

    PubMed Central

    Pearce, Mark S.; Sear, Rebecca

    2015-01-01

    Objectives In high‐income populations, evidence suggests that socioeconomic disadvantage early in life is correlated with reproductive strategy. Children growing up in unfavorable rearing environments tend to experience earlier sexual maturity and first births. Earlier first births may be associated with higher fertility, but links between socioeconomic disadvantage and larger family size have rarely been tested. The pathways through which early disadvantage influences reproduction are unknown. We test whether physiological factors link childhood adversity to age at first birth and total children. Methods Using data from the Newcastle Thousand Families Study, a 1947 British birth cohort, we developed path models to identify possible physiological traits linking childhood socioeconomic status, and poor housing standards, to two reproductive outcomes: age at first birth and total children. We explored birth weight, weight gain after birth, childhood illnesses, body mass index at age 9, age at menarche, and adult height as possible mediators. Results We found direct, negative effects of socioeconomic status (SES) and housing on age at first birth, and of housing on fertility. Although we found links between childhood disadvantage and menarche and height, neither of these were significantly correlated with either reproductive outcome. Age at first birth completely mediates the relationship between childhood adversity and total fertility, which we believe has not been empirically demonstrated before. Conclusions While there are some links between childhood adversity and child health, we find little evidence that physiological pathways, such as child health and growth, link early childhood adversity to reproductive outcomes in this relatively well‐nourished population. Am. J. Hum. Biol. 28:356–363, 2016. © 2015 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc. PMID:26407916

  11. Family Socioeconomic Status and Academic Achievement among Korean Adolescents: Linking Mechanisms of Family Processes and Adolescents' Time Use

    ERIC Educational Resources Information Center

    Bae, Dayoung; Wickrama, K. A. S.

    2015-01-01

    This study examined pathways through which family socioeconomic status may influence adolescents' academic achievement. We focused on parental monitoring and adolescents' after-school time-use patterns as linking mechanisms. Participants were 441 twelve- to fourteen-year-old Korean adolescents who participated in the Korea Welfare Panel Study.…

  12. Socioeconomic pathways to depressive symptoms in adulthood: evidence from the National Longitudinal Survey of Youth 1979.

    PubMed

    Quesnel-Vallée, Amélie; Taylor, Miles

    2012-03-01

    The existence of a direct effect of early socioeconomic position (SEP) on adult mental health outcomes net of adult SEP is still debated. This question demands the explicit modeling of pathways linking early SEP to adult SEP and mental health. In light of this background, we pursue two objectives in this study. First, we examine whether depressive symptoms in adulthood can be fit in a trajectory featuring both an intercept, or baseline range of depressive symptoms that varied between individuals, and a slope describing the average evolution of depressive symptoms over the years. Second, we estimate the direct and indirect pathways linking early SEP, respondents' education and adult household income, with a particular focus on whether early SEP retains a significant direct effect on the trajectory of depressive symptoms once adult SEP is entered into the pathway model. Drawing from 29 years of cohort data from the National Longitudinal Survey of Youth 1979, a survey that has been following a national probability sample of American civilian and military youth (Zagorsky and White, 1999), we used structural equation models to estimate the pathways between parents' education, respondent's education, and latent growth curves of household income and depressive symptoms. We found that the effect of parents' education was entirely mediated by respondent's education. In turn, the effect of respondent's education was largely mediated by household income. In conclusion, our findings showed that the socioeconomic attainment process that is rooted in parents' education and leads to respondent's education and then to household income is a crucial pathway for adult mental health. These results suggest that increasing educational opportunities may be an effective policy to break the intergenerational transmission of low socioeconomic status and poor mental health.

  13. How Many Pathways Underlie Socioeconomic Differences in the Development of Cognition and Achievement?

    PubMed

    Tucker-Drob, Elliot M

    2013-06-01

    Children whose parents have higher education enjoy greater age-linked gains in cognitive abilities and academic achievement. Different researchers have typically focused on different outcomes, and the extent to which parental education relates to multiple child outcomes via a single developmental pathway has received little empirical attention. This issue was examined by applying common factor structural equation models to a large (N = 4,810) nationally representative sample of kindergarten through 12(th) grade children, who were measured on 6 distinct cognitive abilities and 5 distinct forms of knowledge and academic achievement. Results indicated that a single pathway accounted for the relations between parental education and age differences in children's cognitive abilities. However, additional unique pathways were necessary to account for the relations between parental education and age differences in academic knowledge and mathematics. These results suggest that while socioeconomic differences are largely manifest in global aspects of cognitive development, they have incremental relations with some forms of academic achievement. PMID:23710118

  14. TIME PERSPECTIVE AND SOCIOECONOMIC STATUS: A LINK TO SOCIOECONOMIC DISPARITIES IN HEALTH?

    PubMed Central

    Ward, M. M.; Guthrie, Lori C; Butler, Stephen C

    2009-01-01

    Time perspective is a measure of the degree to which one’s thinking is motivated by considerations of the future, present, or past. Time perspective has been proposed as a potential mediator of socioeconomic disparities in health because it has been associated with health behaviors and is presumed to vary with socioeconomic status. In this cross-sectional community-based survey of respondents recruited from hair salons and barber shops in a suburb of Washington DC, we examined the association between time perspective and both education level and occupation. We asked participants (N = 525) to complete a questionnaire that included three subscales (future, present-fatalistic, and present-hedonistic) of the Zimbardo Time Perspective Inventory. Participants with more formal education and those with professional occupations had higher scores on the future time perspective subscale, and lower scores on the present-fatalistic subscale, than participants with less formal education or a non-professional occupation. Present-fatalistic scores were also higher among participants whose parents had less formal education. Present-hedonistic scores were not associated with either education level or professional occupation. Time perspective scores were not independently associated with the likelihood of obesity, smoking, or exercise. In this community sample, future time perspective was associated with current socioeconomic status, and past-fatalistic time perspective was associated with both current and childhood socioeconomic status. PMID:19394738

  15. Multiple Pathways Linking Racism to Health Outcomes.

    PubMed

    Harrell, Camara Jules P; Burford, Tanisha I; Cage, Brandi N; Nelson, Travette McNair; Shearon, Sheronda; Thompson, Adrian; Green, Steven

    2011-04-15

    This commentary discusses advances in the conceptual understanding of racism and selected research findings in the social neurosciences. The traditional stress and coping model holds that racism constitutes a source of aversive experiences that, when perceived by the individual, eventually lead to poor health outcomes. Current evidence points to additional psychophysiological pathways linking facets of racist environments with physiological reactions that contribute to disease. The alternative pathways emphasize prenatal experiences, subcortical emotional neural circuits, conscious and preconscious emotion regulation, perseverative cognitions, and negative affective states stemming from racist cognitive schemata. Recognition of these pathways challenges change agents to use an array of cognitive and self-controlling interventions in mitigating racism's impact. Additionally, it charges policy makers to develop strategies that eliminate deep-seated structural aspects of racism in society.

  16. Pathways from childhood abuse and other adversities to adult health risks: The role of adult socioeconomic conditions.

    PubMed

    Font, Sarah A; Maguire-Jack, Kathryn

    2016-01-01

    Adverse childhood experiences (ACEs), including child abuse, have been linked with poor health outcomes in adulthood. The mechanisms that explain these relations are less understood. This study assesses whether associations of ACEs and health risks are mediated by adult socioeconomic conditions, and whether these pathways are different for maltreatment than for other types of adversities. Using the Behavioral Risk Factor Surveillance System 2012 survey (N=29,229), we employ structural equation modeling to (1) estimate associations of the number and type of ACEs with five health risks-depression, obesity, tobacco use, binge drinking, and self-reported sub-optimal health; and (2) assess whether adult socioeconomic conditions-marriage, divorce and separation, educational attainment, income and insurance status-mediate those associations. Findings suggest both direct and indirect associations between ACEs and health risks. At high numbers of ACEs, 15-20% of the association between number of ACEs and adult health risks was attributable to socioeconomic conditions. Associations of three ACEs (exposure to domestic violence, parental divorce, and residing with a person who was incarcerated) with health risks were nearly entirely explained by socioeconomic conditions in adulthood. However, child physical, emotional, and sexual abuse were significantly associated with several adult health risks, beyond the effects of other adversities, and socioeconomic conditions explained only a small portion of these associations. These findings suggest that the pathways to poor adult health differ by types of ACEs, and that childhood abuse is more likely than other adversities to have a direct impact.

  17. kpath: integration of metabolic pathway linked data

    PubMed Central

    Navas-Delgado, Ismael; García-Godoy, María Jesús; López-Camacho, Esteban; Rybinski, Maciej; Reyes-Palomares, Armando; Medina, Miguel Ángel; Aldana-Montes, José F.

    2015-01-01

    In the last few years, the Life Sciences domain has experienced a rapid growth in the amount of available biological databases. The heterogeneity of these databases makes data integration a challenging issue. Some integration challenges are locating resources, relationships, data formats, synonyms or ambiguity. The Linked Data approach partially solves the heterogeneity problems by introducing a uniform data representation model. Linked Data refers to a set of best practices for publishing and connecting structured data on the Web. This article introduces kpath, a database that integrates information related to metabolic pathways. kpath also provides a navigational interface that enables not only the browsing, but also the deep use of the integrated data to build metabolic networks based on existing disperse knowledge. This user interface has been used to showcase relationships that can be inferred from the information available in several public databases. Database URL: The public Linked Data repository can be queried at http://sparql.kpath.khaos.uma.es using the graph URI “www.khaos.uma.es/metabolic-pathways-app”. The GUI providing navigational access to kpath database is available at http://browser.kpath.khaos.uma.es. PMID:26055101

  18. kpath: integration of metabolic pathway linked data.

    PubMed

    Navas-Delgado, Ismael; García-Godoy, María Jesús; López-Camacho, Esteban; Rybinski, Maciej; Reyes-Palomares, Armando; Medina, Miguel Ángel; Aldana-Montes, José F

    2015-01-01

    In the last few years, the Life Sciences domain has experienced a rapid growth in the amount of available biological databases. The heterogeneity of these databases makes data integration a challenging issue. Some integration challenges are locating resources, relationships, data formats, synonyms or ambiguity. The Linked Data approach partially solves the heterogeneity problems by introducing a uniform data representation model. Linked Data refers to a set of best practices for publishing and connecting structured data on the Web. This article introduces kpath, a database that integrates information related to metabolic pathways. kpath also provides a navigational interface that enables not only the browsing, but also the deep use of the integrated data to build metabolic networks based on existing disperse knowledge. This user interface has been used to showcase relationships that can be inferred from the information available in several public databases. PMID:26055101

  19. kpath: integration of metabolic pathway linked data.

    PubMed

    Navas-Delgado, Ismael; García-Godoy, María Jesús; López-Camacho, Esteban; Rybinski, Maciej; Reyes-Palomares, Armando; Medina, Miguel Ángel; Aldana-Montes, José F

    2015-01-01

    In the last few years, the Life Sciences domain has experienced a rapid growth in the amount of available biological databases. The heterogeneity of these databases makes data integration a challenging issue. Some integration challenges are locating resources, relationships, data formats, synonyms or ambiguity. The Linked Data approach partially solves the heterogeneity problems by introducing a uniform data representation model. Linked Data refers to a set of best practices for publishing and connecting structured data on the Web. This article introduces kpath, a database that integrates information related to metabolic pathways. kpath also provides a navigational interface that enables not only the browsing, but also the deep use of the integrated data to build metabolic networks based on existing disperse knowledge. This user interface has been used to showcase relationships that can be inferred from the information available in several public databases.

  20. Cascading events in linked ecological and socioeconomic systems

    USGS Publications Warehouse

    Peters, Debra P. C.; Sala, O.E.; Allen, C.D.; Covich, A.; Brunson, M.

    2007-01-01

    Cascading events that start at small spatial scales and propagate non-linearly through time to influence larger areas often have major impacts on ecosystem goods and services. Events such as wildfires and hurricanes are increasing in frequency and magnitude as systems become more connected through globalization processes. We need to improve our understanding of these events in order to predict their occurrence, minimize potential impacts, and allow for strategic recovery. Here, we synthesize information about cascading events in systems located throughout the Americas. We discuss a variety of examples of cascading events that share a common feature: they are often driven by linked ecological and human processes across scales. In this era of globalization, we recommend studies that explicitly examine connections across scales and examine the role of connectivity among non-contiguous as well as contiguous areas. ?? The Ecological Society of America.

  1. Socioeconomic Risk Moderates the Link between Household Chaos and Maternal Executive Function

    PubMed Central

    Deater-Deckard, Kirby; Chen, Nan; Wang, Zhe; Bell, Martha Ann

    2012-01-01

    We examined the link between household chaos (i.e., noise, clutter, disarray, lack of routines) and maternal executive function (i.e., effortful regulation of attention and memory), and whether it varied as a function of socioeconomic risk (i.e., single parenthood, lower mother and father educational attainment, housing situation, and father unemployment). We hypothesized that: 1) higher levels of household chaos would be linked with poorer maternal executive function, even when controlling for other measures of cognitive functioning (e.g., verbal ability), and 2) this link would be strongest in the most socioeconomically distressed or lowest-socioeconomic status households. The diverse sample included 153 mothers from urban and rural areas who completed a questionnaire and a battery of cognitive executive function tasks and a verbal ability task in the laboratory. Results were mixed for hypothesis 1, and consistent with hypothesis 2. Two-thirds of the variance overlapped between household chaos and maternal executive function, but only in families with high levels of socioeconomic risk. This pattern was not found for chaos and maternal verbal ability, suggesting that the potentially deleterious effects of household chaos may be specific to maternal executive function. The findings implicate household chaos as a powerful statistical predictor of maternal executive function in socioeconomically distressed contexts. PMID:22563703

  2. Enhancing the Quantitative Representation of Socioeconomic Conditions in the Shared Socio-economic Pathways (SSPs) using the International Futures Model

    NASA Astrophysics Data System (ADS)

    Rothman, D. S.; Siraj, A.; Hughes, B.

    2013-12-01

    The international research community is currently in the process of developing new scenarios for climate change research. One component of these scenarios are the Shared Socio-economic Pathways (SSPs), which describe a set of possible future socioeconomic conditions. These are presented in narrative storylines with associated quantitative drivers. The core quantitative drivers include total population, average GDP per capita, educational attainment, and urbanization at the global, regional, and national levels. At the same time there have been calls, particularly by the IAV community, for the SSPs to include additional quantitative information on other key social factors, such as income inequality, governance, health, and access to key infrastructures, which are discussed in the narratives. The International Futures system (IFs), based at the Pardee Center at the University of Denver, is able to provide forecasts of many of these indicators. IFs cannot use the SSP drivers as exogenous inputs, but we are able to create development pathways that closely reproduce the core quantitative drivers defined by the different SSPs, as well as incorporating assumptions on other key driving factors described in the qualitative narratives. In this paper, we present forecasts for additional quantitative indicators based upon the implementation of the SSP development pathways in IFs. These results will be of value to many researchers.

  3. Uncertainty in Socioeconomic Pathways and Their Implications for Climate Forcing and Analysis—the Shared Socioeconomic Scenarios (SSPs)

    NASA Astrophysics Data System (ADS)

    Edmonds, J.

    2014-12-01

    The Representative Concentration Pathways (RCPs; Moss, et al., 2010; van Vuuren, et al., 2011) were designed to span the range of anthropogenic climate forcing that existed in the literature. While these scenarios serve to reflect uncertainty in the domain of climate forcing, they are far less useful in exploring the range of potential future socioeconomic developments that might be experienced, and which might form the background from which climate forcing might emerge and against which climate impacts and adaptation might be experienced. A set of "Shared Socioeconomic Pathways" (SSPs) have been proposed, Ebi, et al., (2015), to address this deficiency. This architecture is being implemented in quantitative scenarios of human energy, economic, and land systems by researchers. This presentation provides an update on community quantitative implementation of the SSPs. References: Ebi, Kristie L., Stephane Hallegatte, Tom Kram, Nigel W. Arnell, Timothy R. Carter, Jae Edmonds, Elmar Kriegler, et al., A new scenario framework for climate change research: background, process, and future directions, Climatic Change (2014) 122:363-372. DOI 10.1007/s10584-013-0912-3 Moss, Richard H., Jae A. Edmonds, Kathy A. Hibbard, Martin R. Manning, Steven K. Rose, Detlef P. Van Vuuren, Timothy R. Carter et al. "The next generation of scenarios for climate change research and assessment." Nature 463, no. 7282 (2010): 747-756. Van Vuuren, Detlef P., Jae Edmonds, Mikiko Kainuma, Keywan Riahi, Allison Thomson, Kathy Hibbard, George C. Hurtt et al. "The representative concentration pathways: an overview." Climatic Change 109 (2011): 5-31.

  4. Gender differences in the link between childhood socioeconomic conditions and heart attack risk in adulthood.

    PubMed

    Hamil-Luker, Jenifer; O'Rand, Angela M

    2007-02-01

    A growing body of evidence shows that childhood socioeconomic status (SES) is predictive of disease risk in later life, with those from the most disadvantaged backgrounds more likely to experience poor adult-health outcomes. Most of these studies, however are based on middle-aged male populations and pay insufficient attention to the pathways between childhood risks and specific adult disorders. This article examines gender differences in the link between childhood SES and heart attack risk trajectories and the mechanisms by which early environments affect future disease risk. By using methods that model both latent and path-specific influences, we identify heterogeneity in early life conditions and human, social, and health capital in adulthood that contribute to diverse heart attack risk trajectories between and among men and women as they age into their 60s and 70s. We find that key risk factors for heart attack operate differently for men and women. For men, childhood SES does not differentiate those at low, increasing, and high risk for heart attack. In contrast, women who grew up without a father and/or under adverse economic conditions are the most likely to experience elevated risk for heart attack, even after we adjust for the unequal distribution of working and living conditions, social relationships, access to health care, and adult lifestyle behaviors that influence health outcomes.

  5. Pathways in heart failure disease management across socioeconomic spectra.

    PubMed

    Hebert, Kathy; Gogichaishvili, Ilia; Gopie, Stephanie; Arcement, Lee

    2011-12-01

    Caring for heart failure patients with a low socioeconomic status presents a unique set of challenges for health care providers. Heart failure disease management programs can integrate the use of teaching DVDs to overcome deficiencies in health literacy and take advantage of the Wal-Mart/Target $4 dollar medication program to provide life-saving medical therapy. In addition, open discussions with the patient and family regarding the costs of medications and the reality of what they can afford to pay monthly on a long term basis can guide the physician to prescribing medications by prioritizing use with a focus on evidence-based data for the medications with the highest mortality reduction. Finally, connecting inpatient visits to outpatient visits through the use of electronic medical records systems can facilitate avoidance of unnecessary repeat lab and diagnostic testing.

  6. Pathways in heart failure disease management across socioeconomic spectra.

    PubMed

    Hebert, Kathy; Gogichaishvili, Ilia; Gopie, Stephanie; Arcement, Lee

    2011-12-01

    Caring for heart failure patients with a low socioeconomic status presents a unique set of challenges for health care providers. Heart failure disease management programs can integrate the use of teaching DVDs to overcome deficiencies in health literacy and take advantage of the Wal-Mart/Target $4 dollar medication program to provide life-saving medical therapy. In addition, open discussions with the patient and family regarding the costs of medications and the reality of what they can afford to pay monthly on a long term basis can guide the physician to prescribing medications by prioritizing use with a focus on evidence-based data for the medications with the highest mortality reduction. Finally, connecting inpatient visits to outpatient visits through the use of electronic medical records systems can facilitate avoidance of unnecessary repeat lab and diagnostic testing. PMID:22089272

  7. Extending the Shared Socioeconomic Pathways for sub-national impacts, adaptation, and vulnerability studies

    SciTech Connect

    Absar, Syeda Mariya; Preston, Benjamin L.

    2015-05-25

    The exploration of alternative socioeconomic futures is an important aspect of understanding the potential consequences of climate change. While socioeconomic scenarios are common and, at times essential, tools for the impact, adaptation and vulnerability and integrated assessment modeling research communities, their approaches to scenario development have historically been quite distinct. However, increasing convergence of impact, adaptation and vulnerability and integrated assessment modeling research in terms of scales of analysis suggests there may be value in the development of a common framework for socioeconomic scenarios. The Shared Socioeconomic Pathways represents an opportunity for the development of such a common framework. However, the scales at which these global storylines have been developed are largely incommensurate with the sub-national scales at which impact, adaptation and vulnerability, and increasingly integrated assessment modeling, studies are conducted. Our objective for this study was to develop sub-national and sectoral extensions of the global SSP storylines in order to identify future socioeconomic challenges for adaptation for the U.S. Southeast. A set of nested qualitative socioeconomic storyline elements, integrated storylines, and accompanying quantitative indicators were developed through an application of the Factor-Actor-Sector framework. Finally, in addition to revealing challenges and opportunities associated with the use of the SSPs as a basis for more refined scenario development, this study generated sub-national storyline elements and storylines that can subsequently be used to explore the implications of alternative subnational socioeconomic futures for the assessment of climate change impacts and adaptation.

  8. Socioeconomic Status and the Health of Youth: A Multilevel, Multidomain Approach to Conceptualizing Pathways

    ERIC Educational Resources Information Center

    Schreier, Hannah M. C.; Chen, Edith

    2013-01-01

    Previous research has clearly established associations between low socioeconomic status (SES) and poor youth physical health outcomes. This article provides an overview of the main pathways through which low SES environments come to influence youth health. We focus on 2 prevalent chronic health problems in youth today, asthma and obesity. We…

  9. Mining gene link information for survival pathway hunting.

    PubMed

    Jing, Gao-Jian; Zhang, Zirui; Wang, Hong-Qiang; Zheng, Hong-Mei

    2015-08-01

    This study proposes a gene link-based method for survival time-related pathway hunting. In this method, the authors incorporate gene link information to estimate how a pathway is associated with cancer patient's survival time. Specifically, a gene link-based Cox proportional hazard model (Link-Cox) is established, in which two linked genes are considered together to represent a link variable and the association of the link with survival time is assessed using Cox proportional hazard model. On the basis of the Link-Cox model, the authors formulate a new statistic for measuring the association of a pathway with survival time of cancer patients, referred to as pathway survival score (PSS), by summarising survival significance over all the gene links in the pathway, and devise a permutation test to test the significance of an observed PSS. To evaluate the proposed method, the authors applied it to simulation data and two publicly available real-world gene expression data sets. Extensive comparisons with previous methods show the effectiveness and efficiency of the proposed method for survival pathway hunting. PMID:26243831

  10. Extending the Shared Socioeconomic Pathways for sub-national impacts, adaptation, and vulnerability studies

    DOE PAGES

    Absar, Syeda Mariya; Preston, Benjamin L.

    2015-05-25

    The exploration of alternative socioeconomic futures is an important aspect of understanding the potential consequences of climate change. While socioeconomic scenarios are common and, at times essential, tools for the impact, adaptation and vulnerability and integrated assessment modeling research communities, their approaches to scenario development have historically been quite distinct. However, increasing convergence of impact, adaptation and vulnerability and integrated assessment modeling research in terms of scales of analysis suggests there may be value in the development of a common framework for socioeconomic scenarios. The Shared Socioeconomic Pathways represents an opportunity for the development of such a common framework. However,more » the scales at which these global storylines have been developed are largely incommensurate with the sub-national scales at which impact, adaptation and vulnerability, and increasingly integrated assessment modeling, studies are conducted. Our objective for this study was to develop sub-national and sectoral extensions of the global SSP storylines in order to identify future socioeconomic challenges for adaptation for the U.S. Southeast. A set of nested qualitative socioeconomic storyline elements, integrated storylines, and accompanying quantitative indicators were developed through an application of the Factor-Actor-Sector framework. Finally, in addition to revealing challenges and opportunities associated with the use of the SSPs as a basis for more refined scenario development, this study generated sub-national storyline elements and storylines that can subsequently be used to explore the implications of alternative subnational socioeconomic futures for the assessment of climate change impacts and adaptation.« less

  11. Rubric for Linked Learning Pathway Certification

    ERIC Educational Resources Information Center

    LaPlante, Arlene; Stearns, Roman

    2010-01-01

    This rubric was created to help pathway teams as they work together to develop and improve a comprehensive program of study. Specifically, the rubric can serve as a tool for: (1) Visioning; (2) Self-assessment; (3) Planning; and (4) Quality review. ConnectEd designed this rubric to be used in coordination with the Certification Criteria for Linked…

  12. Pathways between Socioeconomic Disadvantage and Childhood Growth in the Scottish Longitudinal Study, 1991–2001

    PubMed Central

    Silverwood, Richard J.; Williamson, Lee; Grundy, Emily M.; De Stavola, Bianca L.

    2016-01-01

    Socioeconomically disadvantaged children are more likely to be of shorter stature and overweight, leading to greater risk of obesity in adulthood. Disentangling the mediatory pathways between socioeconomic disadvantage and childhood size may help in the development of appropriate policies aimed at reducing these health inequalities. We aimed to elucidate the putative mediatory role of birth weight using a representative sample of the Scottish population born 1991–2001 (n = 16,628). Estimated height and overweight/obesity at age 4.5 years were related to three measures of socioeconomic disadvantage (mother’s education, Scottish Index of Multiple Deprivation, synthetic weekly income). Mediation was examined using two approaches: a ‘traditional’ mediation analysis and a counterfactual-based mediation analysis. Both analyses identified a negative effect of each measure of socioeconomic disadvantage on height, mediated to some extent by birth weight, and a positive ‘direct effect’ of mother’s education and Scottish Index of Multiple Deprivation on overweight/obesity, which was partly counterbalanced by a negative ‘indirect effect’. The extent of mediation estimated when adopting the traditional approach was greater than when adopting the counterfactual-based approach because of inappropriate handling of intermediate confounding in the former. Our findings suggest that higher birth weight in more disadvantaged groups is associated with reduced social inequalities in height but also with increased inequalities in overweight/obesity. PMID:27736963

  13. A systematic review of the relationships between social capital and socioeconomic inequalities in health: a contribution to understanding the psychosocial pathway of health inequalities

    PubMed Central

    2013-01-01

    Introduction Recent research on health inequalities moves beyond illustrating the importance of psychosocial factors for health to a more in-depth study of the specific psychosocial pathways involved. Social capital is a concept that captures both a buffer function of the social environment on health, as well as potential negative effects arising from social inequality and exclusion. This systematic review assesses the current evidence, and identifies gaps in knowledge, on the associations and interactions between social capital and socioeconomic inequalities in health. Methods Through this systematic review we identified studies on the interactions between social capital and socioeconomic inequalities in health published before July 2012. Results The literature search resulted in 618 studies after removal of duplicates, of which 60 studies were eligible for analysis. Self-reported measures of health were most frequently used, together with different bonding, bridging and linking components of social capital. A large majority, 56 studies, confirmed a correlation between social capital and socioeconomic inequalities in health. Twelve studies reported that social capital might buffer negative health effects of low socioeconomic status and five studies concluded that social capital has a stronger positive effect on health for people with a lower socioeconomic status. Conclusions There is evidence for both a buffer effect and a dependency effect of social capital on socioeconomic inequalities in health, although the studies that assess these interactions are limited in number. More evidence is needed, as identified hypotheses have implications for community action and for action on the structural causes of social inequalities. PMID:23870068

  14. Tantalizing Thanatos: unexpected links in death pathways.

    PubMed

    Cohen, Isabelle; Castedo, Maria; Kroemer, Guido

    2002-07-01

    Cell death is most frequently the result of apoptosis, an event that is often controlled by mitochondrial membrane permeabilization (MMP). Recent data reveal unexpected functional links between apoptosis and autophagic cell death, in the sense that MMP can trigger autophagy of damaged mitochondria. Conversely, one of the major signal-transducing molecules involved in the activation of autophagy during apoptosis--the so-called DAP kinase--can induce cell death through MMP. Connections are also emerging between apoptosis, autophagy, replicative senescence and cancer-specific metabolic changes. PMID:12185842

  15. Accelerated ageing and renal dysfunction links lower socioeconomic status and dietary phosphate intake

    PubMed Central

    McClelland, Ruth; Christensen, Kelly; Mohammed, Suhaib; McGuinness, Dagmara; Cooney, Josephine; Bakshi, Andisheh; Demou, Evangelia; MacDonald, Ewan; Caslake, Muriel; Stenvinkel, Peter; Shiels, Paul G.

    2016-01-01

    Background We have sought to explore the impact of dietary Pi intake on human age related health in the pSoBid cohort (n=666) to explain the disparity between health and deprivation status in this cohort. As hyperphosphataemia is a driver of accelerated ageing in rodent models of progeria we tested whether variation in Pi levels in man associate with measures of biological ageing and health. Results We observed significant relationships between serum Pi levels and markers of biological age (telomere length (p=0.040) and DNA methylation content (p=0.028), gender and chronological age (p=0.032). When analyses were adjusted for socio-economic status and nutritional factors, associations were observed between accelerated biological ageing (telomere length, genomic methylation content) and dietary derived Pi levels among the most deprived males, directly related to the frequency of red meat consumption. Conclusions Accelerated ageing is associated with high serum Pi levels and frequency of red meat consumption. Our data provide evidence for a mechanistic link between high intake of Pi and age-related morbidities tied to socio-economic status. PMID:27132985

  16. Visionmaker NYC: A bottom-up approach to finding shared socioeconomic pathways in New York City

    NASA Astrophysics Data System (ADS)

    Sanderson, E. W.; Fisher, K.; Giampieri, M.; Barr, J.; Meixler, M.; Allred, S. B.; Bunting-Howarth, K. E.; DuBois, B.; Parris, A. S.

    2015-12-01

    Visionmaker NYC is a free, public participatory, bottom-up web application to develop and share climate mitigation and adaptation strategies for New York City neighborhoods. The goal is to develop shared socioeconomic pathways by allowing a broad swath of community members - from schoolchildren to architects and developers to the general public - to input their concepts for a desired future. Visions are comprised of climate scenarios, lifestyle choices, and ecosystem arrangements, where ecosystems are broadly defined to include built ecosystems (e.g. apartment buildings, single family homes, etc.), transportation infrastructure (e.g. highways, connector roads, sidewalks), and natural land cover types (e.g. wetlands, forests, estuary.) Metrics of water flows, carbon cycling, biodiversity patterns, and population are estimated for the user's vision, for the same neighborhood today, and for that neighborhood as it existed in the pre-development state, based on the Welikia Project (welikia.org.) Users can keep visions private, share them with self-defined groups of other users, or distribute them publicly. Users can also propose "challenges" - specific desired states of metrics for specific parts of the city - and others can post visions in response. Visionmaker contributes by combining scenario planning, scientific modelling, and social media to create new, wide-open possibilities for discussion, collaboration, and imagination regarding future, shared socioeconomic pathways.

  17. Adolescent Overweight and Obesity: Links to Socioeconomic Status and Fruit and Vegetable Intakes.

    PubMed

    You, Jihyun; Choo, Jina

    2016-03-09

    Whether adolescent overweight/obesity is linked to socioeconomic status (SES) and fruit and vegetable (F/V) intakes has not been confirmed. We aimed to determine whether there is an association between SES and adolescent overweight/obesity and to test the mediating effect of F/V intakes. This cross-sectional study included the data of 63,111 adolescents extracted from the 2013 Korea Youth Risk Behavior Web-based Survey. Overweight/obesity was defined as a body mass index ≥ 85th percentile, while F/V intakes were categorized as high (recommended levels: ≥ 1 fruit serving and ≥ 3 vegetable servings per day) versus low. Among girls, low SES (beta = 0.50, p < 0.001) and F/V intakes (beta = -0.17, p = 0.038) were both significantly associated with overweight/obesity; the former association was significantly mediated by F/V intakes (Sobel test: z = 2.00, p = 0.046). Among boys, neither SES nor F/V intakes was significantly associated with overweight/obesity. Adolescent overweight/obesity was significantly linked to low SES and F/V intakes among girls only; low SES indirectly increased the risk of overweight/obesity via low F/V intakes. Therefore, promoting F/V intakes for socially disadvantaged girls should be prioritized as a population-based strategy for preventing adolescent overweight/obesity in South Korea.

  18. Socio-Economic Importance of Links between Campuses, Communities, and International Students and Alumni: Perceptions of Collegiate and Community Leaders.

    ERIC Educational Resources Information Center

    Smith, Harold A.

    A Mississippi State University study investigated the perceptions of community and higher education leaders (N=197) concerning the potential socio-economic importance to Americans of establishing continuing links among communities, colleges and universities, and international students and alumni. Individuals surveyed include academic vice…

  19. Scenarios for the risk of hunger in the twenty-first century using Shared Socioeconomic Pathways

    NASA Astrophysics Data System (ADS)

    Hasegawa, Tomoko; Fujimori, Shinichiro; Takahashi, Kiyoshi; Masui, Toshihiko

    2015-01-01

    Shared socioeconomic pathways (SSPs) are being developed internationally for cross-sectoral assessments of climate change impacts, adaptation, and mitigation. These are five scenarios that include both qualitative and quantitative information for mitigation and adaptation challenges to climate change. In this study, we quantified scenarios for the risk of hunger in the 21st century using SSPs, and clarified elements that influence future hunger risk. There were two primary findings: (1) risk of hunger in the 21st-century greatly differed among five SSPs; and (2) population growth, improvement in the equality of food distribution within a country, and increases in food consumption mainly driven by income growth greatly influenced future hunger risk and were important elements in its long-term assessment.

  20. Socio-economic disparities in preterm birth: causal pathways and mechanisms.

    PubMed

    Kramer, M S; Goulet, L; Lydon, J; Séguin, L; McNamara, H; Dassa, C; Platt, R W; Chen, M F; Gauthier, H; Genest, J; Kahn, S; Libman, M; Rozen, R; Masse, A; Miner, L; Asselin, G; Benjamin, A; Klein, J; Koren, G

    2001-07-01

    Preterm birth is the leading cause of infant mortality in industrialised societies. Its incidence is greatly increased among the socially disadvantaged, but the reasons for this excess are unclear and have been relatively unexplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involves chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasing hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy. The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested case-control study within a prospectively recruited and followed cohort of pregnant women with singleton pregnancies who deliver at one of four Montreal hospitals that serve an ethnically and socio-economically diverse population. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to assess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and performs a digital and speculum examination to measure cervical length and vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin. After delivery, each case (delivery at < 37 completed weeks following spontaneous onset of labour or prelabour rupture of membranes

  1. A Framework for Developing Indicators Linking Socio-Economic and Ecological Impacts of Water Funds

    NASA Astrophysics Data System (ADS)

    Bremer, L.; Game, E.; Calvache, A.; Moreno, P.; Morales, A.; Rivera, B.; Rodriguez, L. M.

    2014-12-01

    Growing interest in the equity and sustainability of water funds and other investment in watershed services programs has spurred interest in evaluation of program impacts on ecosystem services and human well-being. Yet, programs often lack a systematic framework to select indicators that are both important to stakeholders and relevant to hypothesized program impact. To fill this gap, we developed a participatory indicator selection methodology and piloted it in Fondo Agua por La Vida y la Sostenibilidad in the East Cauca Valley Colombia. We started by linking program activities to anticipated ecological and socio-economic impacts through stakeholder developed results chains. Using results chains as the framework, we constructed fuzzy cognitive models to explore the relative impact of program activities on social and ecological attributes. To prioritize indicators to monitor, we combined our fuzzy modelling results with an assessment of the perceived importance of different attributes for stakeholders in the water fund. We used the selected indicators to design a monitoring program that will allow the water fund to track and communicate its impact over the long-term.

  2. Alternative futures for societal change: The Shared Socio-Economic Pathways (SSPs) (Invited)

    NASA Astrophysics Data System (ADS)

    O'Neill, B. C.

    2013-12-01

    Deciding how best to respond to the challenge of climate change requires anticipating not only how climate might change in the future, but how society might change as well. Changes in population and economic growth, innovation, technological development, governance, culture, and lifestyle all will affect the energy use and land use that drive climate change, as well as society's capacity to reduce emissions or adapt to climate change impacts. Developing a set of alternative scenarios for societal development is one way to capture and explore the uncertainty in future conditions. The climate change research community has produced a new set of five such scenarios, called Shared Socio-Economic Pathways (SSPs), that is intended to underpin scientific studies, assessments, and policy dialogues for the next decade or more. The SSPs include both qualitative narratives and quantitative projections of key elements such as population, economic growth, urbanization, and educational attainment. They are designed to span a wide range of future conditions in terms of the challenges they present to both adaptation and mitigation. The SSPs are one component of a larger scenario framework which also includes a set of radiative forcing pathways and climate model simulations based on them. Alternative climate futures will be integrated with the alternative societal futures represented by the SSPs to investigate climate change impacts as well as mitigation and adaptation response options.

  3. Extended Shared Socioeconomic Pathways for Coastal Impact Assessment: Spatial Coastal Population Scenarios

    NASA Astrophysics Data System (ADS)

    Merkens, Jan-Ludolf; Reimann, Lena; Hinkel, Jochen; Vafeidis, Athanasios T.

    2016-04-01

    This work extends the Shared Socioeconomic Pathways (SSPs) by developing spatial projections of global coastal population distribution for the five basic SSPs. Based on a series of coastal migration drivers, which were identified from existing literature, we develop coastal narratives for the five basic SSPs (SSP1-5). These narratives account for differences in coastal versus inland population development in urban and rural areas. To spatially distribute population we use the International Institute for Applied Systems Analysis (IIASA) national population and urbanisation projections and employ country-specific growth rates which differ for coastal and inland as well as for urban and rural regions. These rates are derived from spatial analysis of historical population data. We then adjust these rates for each SSP based on the coastal narratives. The resulting global population grids depict the projected distribution of coastal population for each SSP, until the end of the 21st century, at a spatial resolution of 30 arc seconds. These grids exhibit a three- to four-fold increase in coastal population compared to the basic SSPs. Across all SSPs, except for SSP3, coastal population peaks by the middle of the 21st century and declines afterwards. In SSP3 the coastal population grows continuously until 2100. Compared to the base year 2000 the coastal population increases considerably in all SSPs. The extended SSPs are intended to be utilised in Impact, Adaptation and Vulnerability (IAV) assessments as they allow for improved analysis of exposure to sea-level rise and coastal flooding under different physical and socioeconomic scenarios.

  4. A Quantative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population Dynamics

    EPA Science Inventory

    A Quantitative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population DynamicsAn adverse outcome pathway (AOP) is a qualitative description linking a molecular initiating event (MIE) with measureable key events leading to an adverse outcome (AO). ...

  5. Global implementation of two shared socioeconomic pathways for future sanitation and wastewater flows.

    PubMed

    van Puijenbroek, P J T M; Bouwman, A F; Beusen, A H W; Lucas, P L

    2015-01-01

    Households are an important source of nutrient loading to surface water. Sewage systems without or with only primary wastewater treatment are major polluters of surface water. Future emission levels will depend on population growth, urbanisation, increases in income and investments in sanitation, sewage systems and wastewater treatment plants. This study presents the results for two possible shared socioeconomic pathways (SSPs). SSP1 is a scenario that includes improvement of wastewater treatment and SSP3 does not include such improvement, with fewer investments and a higher population growth. The main drivers for the nutrient emission model are population growth, income growth and urbanisation. Under the SSP1 scenario, 5.7 billion people will be connected to a sewage system and for SSP3 this is 5 billion. Nitrogen and phosphorus emissions increase by about 70% under both SSP scenarios, with the largest increase in SSP1. South Asia and Africa have the largest emission increases, in the developed countries decrease the nutrient emissions. The higher emission level poses a risk to ecosystem services.

  6. Investigating the evolution of Shared Socioeconomic Pathways with a large number of scenarios

    NASA Astrophysics Data System (ADS)

    Schweizer, V. J.; Guivarch, C.; Rozenberg, J.

    2013-12-01

    The new scenario framework for climate change research includes alternative possible trends for socioeconomic development called Shared Socioeconomic Pathways (SSPs). The SSPs bear some similarities to other scenarios used for global change research, but they also have important differences. Like the IPCC Special Report on Emissions Scenarios or the Millennium Ecosystem Assessment, SSPs are defined by a scenario logic consisting of two axes. However, these axes define SSPs with respect to their location in an outcome space for challenges to mitigation and to adaptation rather than by their drivers. Open questions for the SSPs include what their drivers are and how the time dimension could be interpreted with the outcomes space. We present a new analytical approach for addressing both questions by studying large numbers of scenarios produced by an integrated assessment model, IMACLIM-R. We systematically generated 432 scenarios and used the SSP framework to classify them by typology. We then analyzed them dynamically, tracing their evolution through the SSP challenges space at annual time steps over the period 2010-2090. Through this approach, we found that many scenarios do not remain fixed to a particular SSP domain; they drift from one domain to another. In papers describing the framework for new scenarios, SSPs are envisioned as hypothetical (counter-factual) reference scenarios that remain fixed in one domain over some time period of interest. However, we conclude that it may be important to also research scenarios that shift across SSP domains. This is relevant for another open question, which is what scenarios are important to explore given their consequences. Through a data mining technique, we uncovered prominent drivers for scenarios that shift across SSP domains. Scenarios with different challenges for adaptation and mitigation (that is, mitigation and adaptation challenges that are not co-varying) were found to be the least stable, and the following

  7. Gridded population projections for the coastal zone under the Shared Socioeconomic Pathways

    NASA Astrophysics Data System (ADS)

    Merkens, Jan-Ludolf; Reimann, Lena; Hinkel, Jochen; Vafeidis, Athanasios T.

    2016-10-01

    Existing quantifications of the Shared Socioeconomic Pathways (SSP) used for climate impact assessment do not account for subnational population dynamics such as coastward-migration that can be critical for coastal impact assessment. This paper extends the SSPs by developing spatial projections of global coastal population distribution for the five basic SSPs. Based on a series of coastal migration drivers we develop coastal narratives for each SSP. These narratives account for differences in coastal and inland population developments in urban and rural areas. To spatially distribute population, we use the International Institute for Applied Systems Analysis (IIASA) national population and urbanisation projections and employ country-specific growth rates, which differ for coastal and inland as well as for urban and rural regions, to project coastal population for each SSP. These rates are derived from spatial analysis of historical population data and adjusted for each SSP based on the coastal narratives. Our results show that, compared to the year 2000 (638 million), the population living in the Low Elevated Coastal Zone (LECZ) increases by 58% to 71% until 2050 and exceeds one billion in all SSPs. By the end of the 21st century, global coastal population declines to 830-907 million in all SSPs except for SSP3, where coastal population growth continues and reaches 1.184 billion. Overall, the population living in the LECZ is higher by 85 to 239 million compared to the original IIASA projections. Asia expects the highest absolute growth (238-303 million), Africa the highest relative growth (153% to 218%). Our results highlight regions where high coastal population growth is expected and will therefore face an increased exposure to coastal flooding.

  8. Spatially explicit global population scenarios consistent with the Shared Socioeconomic Pathways

    NASA Astrophysics Data System (ADS)

    Jones, B.; O'Neill, B. C.

    2016-08-01

    The projected size and spatial distribution of the future population are important drivers of global change and key determinants of exposure and vulnerability to hazards. Spatial demographic projections are widely used as inputs to spatial projections of land use, energy use, and emissions, as well as to assessments of the impacts of extreme events, sea level rise, and other climate-related outcomes. To date, however, there are very few global-scale, spatially explicit population projections, and those that do exist are often based on simple scaling or trend extrapolation. Here we present a new set of global, spatially explicit population scenarios that are consistent with the new Shared Socioeconomic Pathways (SSPs) developed to facilitate global change research. We use a parameterized gravity-based downscaling model to produce projections of spatial population change that are quantitatively consistent with national population and urbanization projections for the SSPs and qualitatively consistent with assumptions in the SSP narratives regarding spatial development patterns. We show that the five SSPs lead to substantially different spatial population outcomes at the continental, national, and sub-national scale. In general, grid cell-level outcomes are most influenced by national-level population change, second by urbanization rate, and third by assumptions about the spatial style of development. However, the relative importance of these factors is a function of the magnitude of the projected change in total population and urbanization for each country and across SSPs. We also demonstrate variation in outcomes considering the example of population existing in a low-elevation coastal zone under alternative scenarios.

  9. Socioeconomic Status and the Health of Youth: A Multi-level, Multi-domain Approach to Conceptualizing Pathways

    PubMed Central

    Schreier, Hannah M. C.; Chen, Edith

    2012-01-01

    Previous research has clearly established associations between low socioeconomic status (SES) and poor youth physical health outcomes. This article provides an overview of the main pathways through which low SES environments come to influence youth health. We focus on two of the most prevalent chronic health problems in youth today, asthma and obesity. We review and propose a model that encompasses (1) multiple levels of influence, including the neighborhood, family and person level, (2) both social and physical domains in the environment, and finally (3) dynamic relationships between these factors. A synthesis of existing research and our proposed model draw attention to the notion of adverse physical and social exposures in youth’s neighborhood environments altering family characteristics and youth psychosocial and behavioral profiles, thereby increasing youth’s risk for health problems. We also note the importance of acknowledging reciprocal influences across levels and domains (e.g., between family and child) that create self-perpetuating patterns of influence that further accentuate the impact of these factors on youth health. Finally, we document that factors across levels can interact (e.g., environmental pollution levels with child stress) to create unique, synergistic effects on youth health. Our model stresses the importance of evaluating influences on youth’s physical health not in isolation but in the context of the broader social and physical environments in which youth live. Understanding the complex relationships between the factors that link low SES to youth’s long-term health trajectories is necessary for the creation and implementation of successful interventions and policies to ultimately reduce health disparities. PMID:22845752

  10. Linking Socioeconomic Status to Social Cognitive Career Theory Factors: A Partial Least Squares Path Modeling Analysis

    ERIC Educational Resources Information Center

    Huang, Jie-Tsuen; Hsieh, Hui-Hsien

    2011-01-01

    The purpose of this study was to investigate the contributions of socioeconomic status (SES) in predicting social cognitive career theory (SCCT) factors. Data were collected from 738 college students in Taiwan. The results of the partial least squares (PLS) analyses indicated that SES significantly predicted career decision self-efficacy (CDSE);…

  11. Brain-Body Pathways Linking Psychological Stress and Physical Health

    PubMed Central

    Gianaros, Peter J.; Wager, Tor D.

    2015-01-01

    Psychological stress is thought to arise from appraisal processes that ascribe threat-related meaning to experiences that tax or exceed our coping ability. Neuroimaging research indicates that these appraisal processes originate in brain systems that also control physiological stress reactions in the body. Separate lines of research in health psychology and behavioral medicine indicate that these physiological stress reactions confer risk for physical disease. Accordingly, integrative research that cuts across historically separated disciplines may help to define the brain-body pathways linking psychological stress to physical health. We describe recent studies aimed at this goal, focusing on studies of the brain bases of stressor-evoked cardiovascular system reactions and heart disease risk. We also outline an interpretive framework for these studies, as well as needs for next-generation models and metrics to better understand how the brain encodes and embodies stress in relation to health. PMID:26279608

  12. Epigenetic pathways through which experiences become linked with biology.

    PubMed

    McGowan, Patrick O; Roth, Tania L

    2015-05-01

    This article highlights the defining principles, progress, and future directions in epigenetics research in relation to this Special Issue. Exciting studies in the fields of neuroscience, psychology, and psychiatry have provided new insights into the epigenetic factors (e.g., DNA methylation) that are responsive to environmental input and serve as biological pathways in behavioral development. Here we highlight the experimental evidence, mainly from animal models, that factors such as psychosocial stress and environmental adversity can become encoded within epigenetic factors with functional consequences for brain plasticity and behavior. We also highlight evidence that epigenetic marking of genes in one generation can have consequences for future generations (i.e., inherited), and work with humans linking epigenetics, cognitive dysfunction, and psychiatric disorder. Though epigenetics has offered more of a beginning than an answer to the centuries-old nature-nurture debate, continued research is certain to yield substantial information regarding biological determinants of central nervous system changes and behavior with relevance for the study of developmental psychopathology.

  13. Epigenetic pathways through which experiences become linked with biology.

    PubMed

    McGowan, Patrick O; Roth, Tania L

    2015-05-01

    This article highlights the defining principles, progress, and future directions in epigenetics research in relation to this Special Issue. Exciting studies in the fields of neuroscience, psychology, and psychiatry have provided new insights into the epigenetic factors (e.g., DNA methylation) that are responsive to environmental input and serve as biological pathways in behavioral development. Here we highlight the experimental evidence, mainly from animal models, that factors such as psychosocial stress and environmental adversity can become encoded within epigenetic factors with functional consequences for brain plasticity and behavior. We also highlight evidence that epigenetic marking of genes in one generation can have consequences for future generations (i.e., inherited), and work with humans linking epigenetics, cognitive dysfunction, and psychiatric disorder. Though epigenetics has offered more of a beginning than an answer to the centuries-old nature-nurture debate, continued research is certain to yield substantial information regarding biological determinants of central nervous system changes and behavior with relevance for the study of developmental psychopathology. PMID:25997776

  14. Epigenetic pathways through which experiences become linked with biology

    PubMed Central

    McGowan, Patrick O.; Roth, Tania L.

    2015-01-01

    This article highlights the defining principles, progress, and future directions in epigenetics research in relation to this special issue. Exciting studies in the fields of neuroscience, psychology, and psychiatry have provided new insights into the epigenetic factors (e.g. DNA methylation) that are responsive to environmental input and serve as biological pathways in behavioral development. Here we highlight the experimental evidence, mainly from animal models, that factors such as psychosocial stress and environmental adversity can become encoded within epigenetic factors with functional consequences for brain plasticity and behavior. We also highlight evidence that epigenetic marking of genes in one generation can have consequences for future generations (i.e. inherited), and work with humans linking epigenetics, cognitive dysfunction, and psychiatric disorder. Though epigenetics has offered more of a beginning than an answer to the centuries-old nature-nurture debate, continued research is certain to yield substantial information regarding biological determinants of CNS changes and behavior with relevance for the study of developmental psychopathology. PMID:25997776

  15. Evolutionary bursts in Euphorbia (Euphorbiaceae) are linked with photosynthetic pathway.

    PubMed

    Horn, James W; Xi, Zhenxiang; Riina, Ricarda; Peirson, Jess A; Yang, Ya; Dorsey, Brian L; Berry, Paul E; Davis, Charles C; Wurdack, Kenneth J

    2014-12-01

    The mid-Cenozoic decline of atmospheric CO2 levels that promoted global climate change was critical to shaping contemporary arid ecosystems. Within angiosperms, two CO2 -concentrating mechanisms (CCMs)-crassulacean acid metabolism (CAM) and C4 -evolved from the C3 photosynthetic pathway, enabling more efficient whole-plant function in such environments. Many angiosperm clades with CCMs are thought to have diversified rapidly due to Miocene aridification, but links between this climate change, CCM evolution, and increased net diversification rates (r) remain to be further understood. Euphorbia (∼2000 species) includes a diversity of CAM-using stem succulents, plus a single species-rich C4 subclade. We used ancestral state reconstructions with a dated molecular phylogeny to reveal that CCMs independently evolved 17-22 times in Euphorbia, principally from the Miocene onwards. Analyses assessing among-lineage variation in r identified eight Euphorbia subclades with significantly increased r, six of which have a close temporal relationship with a lineage-corresponding CCM origin. Our trait-dependent diversification analysis indicated that r of Euphorbia CCM lineages is approximately threefold greater than C3 lineages. Overall, these results suggest that CCM evolution in Euphorbia was likely an adaptive strategy that enabled the occupation of increased arid niche space accompanying Miocene expansion of arid ecosystems. These opportunities evidently facilitated recent, replicated bursts of diversification in Euphorbia.

  16. Mediating pathways between parental socio-economic position and allostatic load in mid-life: Findings from the 1958 British birth cohort.

    PubMed

    Barboza Solís, Cristina; Fantin, Romain; Castagné, Raphaële; Lang, Thierry; Delpierre, Cyrille; Kelly-Irving, Michelle

    2016-09-01

    Understanding how human environments affect our health by "getting under the skin" and penetrating the cells, organs and physiological systems of our bodies is a key tenet in public health research. Here, we examine the idea that early life socioeconomic position (SEP) can be biologically embodied, potentially leading to the production of health inequalities across population groups. Allostatic load (AL), a composite measure of overall physiological wear-and-tear, could allow for a better understanding of the potential biological pathways playing a role in the construction of the social gradient in adult health. We investigate the factors mediating the link between two components of parental SEP, maternal education (ME) and parental occupation (PO), and AL at 44 years. Data was used from 7573 members of the 1958 British birth cohort follow-up to age 44. AL was constructed using 14 biomarkers representing four physiological systems. We assessed the contribution of financial/materialist, psychological/psychosocial, educational, and health behaviors/BMI pathways over the life course, in mediating the associations between ME, PO and AL. ME and PO were mediated by three pathways: educational, material/financial, and health behaviors, for both men and women. A better understanding of embodiment processes leading to disease development may contribute to developing adapted public policies aiming to reduce health inequalities. PMID:27485729

  17. Enduring links from childhood mathematics and reading achievement to adult socioeconomic status.

    PubMed

    Ritchie, Stuart J; Bates, Timothy C

    2013-07-01

    Understanding the determinants of socioeconomic status (SES) is an important economic and social goal. Several major influences on SES are known, yet much of the variance in SES remains unexplained. In a large, population-representative sample from the United Kingdom, we tested the effects of mathematics and reading achievement at age 7 on attained SES by age 42. Mathematics and reading ability both had substantial positive associations with adult SES, above and beyond the effects of SES at birth, and with other important factors, such as intelligence. Achievement in mathematics and reading was also significantly associated with intelligence scores, academic motivation, and duration of education. These findings suggest effects of improved early mathematics and reading on SES attainment across the life span.

  18. Global Inequalities in Cervical Cancer Incidence and Mortality are Linked to Deprivation, Low Socioeconomic Status, and Human Development

    PubMed Central

    Singh, Gopal K.; Azuine, Romuladus E.; Siahpush, Mohammad

    2012-01-01

    Objectives This study examined global inequalities in cervical cancer incidence and mortality rates as a function of cross-national variations in the Human Development Index (HDI), socioeconomic factors, Gender Inequality Index (GII), and healthcare expenditure. Methods Age-adjusted incidence and mortality rates were calculated for women in 184 countries using the 2008 GLOBOCAN database, and incidence and mortality trends were analyzed using the WHO cancer mortality database. Log-linear regression was used to model annual trends, while OLS and Poisson regression models were used to estimate the impact of socioeconomic and human development factors on incidence and mortality rates. Results Cervical cancer incidence and mortality rates varied widely, with many African countries such as Guinea, Zambia, Comoros, Tanzania, and Malawi having at least 10-to-20-fold higher rates than several West Asian, Middle East, and European countries, including Iran, Saudi Arabia, Syria, Egypt, and Switzerland. HDI, GII, poverty rate, health expenditure per capita, urbanization, and literacy rate were all significantly related to cervical cancer incidence and mortality, with HDI and poverty rate each explaining >52% of the global variance in mortality. Both incidence and mortality rates increased in relation to lower human development and higher gender inequality levels. A 0.2 unit increase in HDI was associated with a 20% decrease in cervical cancer risk and a 33% decrease in cervical cancer mortality risk. The risk of a cervical cancer diagnosis increased by 24% and of cervical cancer death by 42% for a 0.2 unit increase in GII. Higher health expenditure levels were independently associated with decreased incidence and mortality risks. Conclusions and Public Health Implications Global inequalities in cervical cancer are clearly linked to disparities in human development, social inequality, and living standards. Reductions in cervical cancer rates are achievable by reducing

  19. Links between Socio-Economic Circumstances and Changes in Smoking Behavior in the Mexican Population: 2002–2010

    PubMed Central

    Beltrán-Sánchez, HIRAM; Thomas, DUNCAN; Teruel, GRACIELA; Wheaton, FELICIA; Crimmins, EILEEN M.

    2013-01-01

    While deleterious consequences of smoking on health have been widely publicized, in many developing countries, smoking prevalence is high and increasing. Little is known about the dynamics underlying changes in smoking behavior. This paper examines socio-economic and demographic characteristics associated with smoking initiation and quitting in Mexico between 2002 and 2010. In addition to the influences of age, gender, education, household economic resources and location of residence, changes in marital status, living arrangements and health status are examined. Drawing data from the Mexican Family Life Survey, a rich population-based longitudinal study of individuals, smoking behavior of individuals in 2002 is compared with their behavior in 2010. Logistic models are used to examine socio-demographic and health factors that are associated with initiating and quitting smoking. There are three main findings. First, part of the relationship between education and smoking reflects the role of economic resources. Second, associations of smoking with education and economic resources differ for females and males. Third, there is considerable heterogeneity in the factors linked to smoking behavior in Mexico indicating that the smoking epidemic may be at different stages in different population subgroups. Mexico has recently implemented fiscal policies and public health campaigns aimed at reducing smoking prevalence and discouraging smoking initiation. These programs are likely to be more effective if they target particular socio-economic and demographic sub-groups. PMID:23888371

  20. FLOOD MANAGEMENT: A CASE STUDY TO LINK SOCIO-ECONOMIC AND ENVIRONMENTAL POLICY

    EPA Science Inventory

    Human living standards are inextricably linked through the economy to the integrity of the natural resources from which they are derived. The complex trade-offs needed to shape sustainable living standards will require a much greater ability to predict the consequences of public...

  1. Prematurity, Birth Weight, and Socioeconomic Status Are Linked to Atypical Diurnal Hypothalamic-Pituitary-Adrenal Axis Activity in Young Adults.

    PubMed

    Winchester, Suzy Barcelos; Sullivan, Mary C; Roberts, Mary B; Granger, Douglas A

    2016-02-01

    In a prospective, case-controlled longitudinal design, 180 preterm and fullterm infants who had been enrolled at birth participated in a comprehensive assessment battery at age 23. Of these, 149 young adults, 34 formerly full-term and 115 formerly preterm (22 healthy preterm, 48 with medical complications, 21 with neurological complications, and 24 small for gestational age) donated five saliva samples from a single day that were assayed for cortisol to assess diurnal variation of the hypothalamic-pituitary-adrenal (HPA) axis. Analyses were conducted to determine whether prematurity category, birth weight, and socioeconomic status were associated with differences in HPA axis function. Pre- and perinatal circumstances associated with prematurity influenced the activity of this environmentally sensitive physiological system. Results are consistent with the theory of Developmental Origins of Health and Disease and highlight a possible mechanism for the link between prematurity and health disparities later in life. PMID:26676400

  2. Parenting of divorced mothers as a link between social status and boys' academic outcomes: unpacking the effects of socioeconomic status.

    PubMed

    DeGarmo, D S; Forgatch, M S; Martinez, C R

    1999-01-01

    Socialization theories posit parenting practices as mechanisms linking socioeconomic status (SES) and children's academic outcomes. A mediational parenting model was tested examining separate effects of maternal education, occupation, and income for a sample of 238 divorced or recently separated mothers of 6- to 9-year-old sons. For the SEM path models, each indicator of SES was associated with better parenting, and parenting in turn had indirect effects on achievement through home skill-building activities and school behavior. The direct effect of maternal education on achievement was mediated by home skill-building activities, the direct effect of maternal occupation on achievement was not mediated, and income measures had no direct effects on achievement. These findings underscore the importance of unpacking the effects of SES and the relevance of effective parenting practices as a protective factor in the home and school environment for young boys' school success during postdivorce adjustment.

  3. Central role of the brain in stress and adaptation: Links to socioeconomic status, health, and disease

    PubMed Central

    McEwen, Bruce S.; Gianaros, Peter J.

    2010-01-01

    The brain is the key organ of stress reactivity, coping, and recovery processes. Within the brain, a distributed neural circuitry determines what is threatening and thus stressful to the individual. Instrumental brain systems of this circuitry include the hippocampus, amygdala, and areas of the prefrontal cortex. Together, these systems regulate physiological and behavioral stress processes, which can be adaptive in the short-term and maladaptive in the long-term. Importantly, such stress processes arise from bidirectional patterns of communication between the brain and the autonomic, cardiovascular, and immune systems via neural and endocrine mechanisms underpinning cognition, experience, and behavior. In one respect, these bidirectional stress mechanisms are protective in that they promote short-term adaptation (allostasis). In another respect, however, these stress mechanisms can lead to a long-term dysregulation of allostasis in that they promote maladaptive wear-and-tear on the body and brain under chronically stressful conditions (allostatic load), compromising stress resiliency and health. This review focuses specifically on the links between stress-related processes embedded within the social environment and embodied within the brain, which is viewed as the central mediator and target of allostasis and allostatic load. PMID:20201874

  4. A global water scarcity assessment under Shared Socio-economic Pathways - Part 2: Water availability and scarcity

    NASA Astrophysics Data System (ADS)

    Hanasaki, N.; Fujimori, S.; Yamamoto, T.; Yoshikawa, S.; Masaki, Y.; Hijioka, Y.; Kainuma, M.; Kanamori, Y.; Masui, T.; Takahashi, K.; Kanae, S.

    2013-07-01

    A global water scarcity assessment for the 21st century was conducted under the latest socio-economic scenario for global change studies, namely Shared Socio-economic Pathways (SSPs). SSPs depict five global situations with substantially different socio-economic conditions. In the accompanying paper, a water use scenario compatible with the SSPs was developed. This scenario considers not only quantitative socio-economic factors such as population and electricity production but also qualitative ones such as the degree of technological change and overall environmental consciousness. In this paper, water availability and water scarcity were assessed using a global hydrological model called H08. H08 simulates both the natural water cycle and major human activities such as water abstraction and reservoir operation. It simulates water availability and use at daily time intervals at a spatial resolution of 0.5° × 0.5°. A series of global hydrological simulations were conducted under the SSPs, taking into account different climate policy options and the results of climate models. Water scarcity was assessed using an index termed the Cumulative Abstraction to Demand ratio, which is expressed as the accumulation of daily water abstraction from a river divided by the daily consumption-based potential water demand. This index can be used to express whether renewable water resources are available from rivers when required. The results suggested that by 2071-2100 the population living under severely water-stressed conditions for SSP1-5 will reach 2588-2793 × 106 (39-42% of total population), 3966-4298 × 106 (46-50%), 5334-5643 × 106 (52-55%), 3427-3786 × 106 (40-45%), 3164-3379 × 106 (46-49%) respectively, if climate policies are not adopted. Even in SSP1 (the scenario with least change in water use and climate) global water scarcity increases considerably, as compared to the present-day. This is mainly due to the growth in population and economic activity in developing

  5. A Missing Link for California's Pathways Movement: CTE Instructional Staff

    ERIC Educational Resources Information Center

    Lundy-Wagner, Valerie

    2016-01-01

    Recently, the State of California committed nearly one billion dollars to the development of career and technical education (CTE) pathways that lead to locally relevant, high-growth, high-demand careers. This investment represents a pivot from relatively disjointed approaches to CTE in high schools and community colleges, and reflects an…

  6. Linking multiple pathogenic pathways in Alzheimer’s disease

    PubMed Central

    Bou Khalil, Rami; Khoury, Elie; Koussa, Salam

    2016-01-01

    Alzheimer’s disease (AD) is a chronic neurodegenerative disorder presenting as progressive cognitive decline with dementia that does not, to this day, benefit from any disease-modifying drug. Multiple etiologic pathways have been explored and demonstrate promising solutions. For example, iron ion chelators, such as deferoxamine, are a potential therapeutic solution around which future studies are being directed. Another promising domain is related to thrombin inhibitors. In this minireview, a common pathophysiological pathway is suggested for the pathogenesis of AD to prove that all these mechanisms converge onto the same cascade of neuroinflammatory events. This common pathway is initiated by the presence of vascular risk factors that induce brain tissue hypoxia, which leads to endothelial cell activation. However, the ensuing hypoxia stimulates the production and release of reactive oxygen species and pro-inflammatory proteins. Furthermore, the endothelial activation may become excessive and dysfunctional in predisposed individuals, leading to thrombin activation and iron ion decompartmentalization. The oxidative stress that results from these modifications in the neurovascular unit will eventually lead to neuronal and glial cell death, ultimately leading to the development of AD. Hence, future research in this field should focus on conducting trials with combinations of potentially efficient treatments, such as the combination of intranasal deferoxamine and direct thrombin inhibitors. PMID:27354962

  7. Disentangling the indirect links between socioeconomic status and health: the dynamic roles of work stressors and personal control.

    PubMed

    Christie, Amy M; Barling, Julian

    2009-11-01

    Prior research has documented an indirect link between socioeconomic status (SES) and health, and the goal in this study was to help unravel this phenomenon from a dynamic perspective. The authors hypothesized that SES would be positively related to feelings of personal control and negatively related to perceived work stressors. Drawing on dynamic conceptualizations of these psychosocial factors, they suggest that these psychosocial factors relate to one another over time. Individuals who have higher levels of personal control experience increasingly fewer work stressors over time than do those with lower levels of personal control, and those who experience greater work stressors increasingly perceive less personal control over time than do those with fewer work stressors. Finally, the authors argue that trajectories of personal control and work stressors are associated with the accumulation of health problems over the same period. Their model was tested with 3-wave data (over 4 years) from a nationally representative sample of Canadian employees (N = 3,419). Latent curve modeling provides support for the proposed dynamic model. Conceptual and practical implications are drawn, and suggestions for future research are outlined.

  8. Adolescent work intensity, school performance, and substance use: links vary by race/ethnicity and socioeconomic status.

    PubMed

    Bachman, Jerald G; Staff, Jeremy; O'Malley, Patrick M; Freedman-Doan, Peter

    2013-11-01

    High school students who spend long hours in paid employment during the school year are at increased risk of lower grades and higher substance use, although questions remain about whether these linkages reflect causation or prior differences (selection effects). Questions also remain about whether such associations vary by socioeconomic status (SES) and race/ethnicity. This study examines those questions using nationally representative data from two decades (1991-2010) of annual Monitoring the Future surveys involving about 600,000 students in 10th and 12th grades. White students are consistently more likely than minority students to hold paid employment during the school year. Among White and Asian American students, paid work intensity is negatively related to parental education and grade point averages (GPA) and is positively related to substance use. Also among Whites and Asian Americans, students with the most highly educated parents show the strongest negative relations between work intensity and GPA, whereas the links are weaker for those with less educated parents (i.e., lower SES levels). All of these relations are less evident for Hispanic students and still less evident for African American students. It thus appears that any costs possibly attributable to long hours of student work are most severe for those who are most advantaged--White or Asian American students with highly educated parents. Working long hours is linked with fewer disadvantages among Hispanic students and especially among African American students. Youth employment dropped in 2008-2010, but the relations described above have shown little change over two decades.

  9. CREB pathway links PGE2 signaling with macrophage polarization.

    PubMed

    Luan, Bing; Yoon, Young-Sil; Le Lay, John; Kaestner, Klaus H; Hedrick, Susan; Montminy, Marc

    2015-12-22

    Obesity is thought to promote insulin resistance in part via activation of the innate immune system. Increases in proinflammatory cytokine production by M1 macrophages inhibit insulin signaling in white adipose tissue. In contrast, M2 macrophages have been found to enhance insulin sensitivity in part by reducing adipose tissue inflammation. The paracrine hormone prostaglandin E2 (PGE2) enhances M2 polarization in part through activation of the cAMP pathway, although the underlying mechanism is unclear. Here we show that PGE2 stimulates M2 polarization via the cyclic AMP-responsive element binding (CREB)-mediated induction of Krupple-like factor 4 (KLF4). Targeted disruption of CREB or the cAMP-regulated transcriptional coactivators 2 and 3 (CRTC2/3) in macrophages down-regulated M2 marker gene expression and promoted insulin resistance in the context of high-fat diet feeding. As re-expression of KLF4 rescued M2 marker gene expression in CREB-depleted cells, our results demonstrate the importance of the CREB/CRTC pathway in maintaining insulin sensitivity in white adipose tissue via its effects on the innate immune system.

  10. CREB pathway links PGE2 signaling with macrophage polarization

    PubMed Central

    Luan, Bing; Yoon, Young-Sil; Le Lay, John; Kaestner, Klaus H.; Hedrick, Susan; Montminy, Marc

    2015-01-01

    Obesity is thought to promote insulin resistance in part via activation of the innate immune system. Increases in proinflammatory cytokine production by M1 macrophages inhibit insulin signaling in white adipose tissue. In contrast, M2 macrophages have been found to enhance insulin sensitivity in part by reducing adipose tissue inflammation. The paracrine hormone prostaglandin E2 (PGE2) enhances M2 polarization in part through activation of the cAMP pathway, although the underlying mechanism is unclear. Here we show that PGE2 stimulates M2 polarization via the cyclic AMP-responsive element binding (CREB)-mediated induction of Krupple-like factor 4 (KLF4). Targeted disruption of CREB or the cAMP-regulated transcriptional coactivators 2 and 3 (CRTC2/3) in macrophages down-regulated M2 marker gene expression and promoted insulin resistance in the context of high-fat diet feeding. As re-expression of KLF4 rescued M2 marker gene expression in CREB-depleted cells, our results demonstrate the importance of the CREB/CRTC pathway in maintaining insulin sensitivity in white adipose tissue via its effects on the innate immune system. PMID:26644581

  11. Common developmental pathways link tooth shape to regeneration

    PubMed Central

    Fraser, Gareth J.; Bloomquist, Ryan F.; Streelman, J. Todd

    2013-01-01

    In many non-mammalian vertebrates, adult dentitions result from cyclical rounds of tooth regeneration wherein simple unicuspid teeth are replaced by more complex forms. Therefore and by contrast to mammalian models, the numerical majority of vertebrate teeth develop shape during the process of replacement. Here, we exploit the dental diversity of Lake Malawi cichlid fishes to ask how vertebrates generally replace their dentition and in turn how this process acts to influence resulting tooth morphologies. First, we used immunohistochemistry to chart organogenesis of continually replacing cichlid teeth and discovered an epithelial down-growth that initiates the replacement cycle via a labial proliferation bias. Next, we identified sets of co-expressed genes from common pathways active during de novo, lifelong tooth replacement and tooth morphogenesis. Of note, we found two distinct epithelial cell populations, expressing markers of dental competence and cell potency, which may be responsible for tooth regeneration. Related gene sets were simultaneously active in putative signaling centers associated with the differentiation of replacement teeth with complex shapes. Finally, we manipulated targeted pathways (BMP, FGF, Hh, Notch, Wnt/β-catenin) in vivo with small molecules and demonstrated dose-dependent effects on both tooth replacement and tooth shape. Our data suggest that the processes of tooth regeneration and tooth shape morphogenesis are integrated via a common set of molecular signals. This linkage has subsequently been lost or decoupled in mammalian dentitions where complex tooth shapes develop in first generation dentitions that lack the capacity for lifelong replacement. Our dissection of the molecular mechanics of vertebrate tooth replacement coupled to complex shape pinpoints aspects of odontogenesis that might be re-evolved in the lab to solve problems in regenerative dentistry. PMID:23422830

  12. Neuroplasticity Signaling Pathways Linked to the Pathophysiology of Schizophrenia

    PubMed Central

    Balu, Darrick T.; Coyle, Joseph T.

    2010-01-01

    Schizophrenia is a severe mental illness that afflicts nearly 1% of the world's population. One of the cardinal pathological features of schizophrenia is perturbation in synaptic connectivity. Although the etiology of schizophrenia is unknown, it appears to be a developmental disorder involving the interaction of a potentially large number of risk genes, with no one gene producing a strong effect except rare, highly penetrant copy number variants. The purpose of this review is to detail how putative schizophrenia risk genes (DISC-1, neuregulin/ErbB4, dysbindin, Akt1, BDNF, and NMDA receptor) are involved in regulating neuroplasticity and how alterations in their expression may contribute to the disconnectivity observed in schizophrenia. Moreover, this review highlights how many of these risk genes converge to regulate common neurotransmitter systems and signaling pathways. Future studies aimed at elucidating the functions of these risk genes will provide new insights into the pathophysiology of schizophrenia and will likely lead to the nomination of novel therapeutic targets for restoring proper synaptic connectivity in the brain in schizophrenia and related disorders. PMID:20951727

  13. The ZEB1 pathway links glioblastoma initiation, invasion and chemoresistance

    PubMed Central

    Siebzehnrubl, Florian A; Silver, Daniel J; Tugertimur, Bugra; Deleyrolle, Loic P; Siebzehnrubl, Dorit; Sarkisian, Matthew R; Devers, Kelly G; Yachnis, Antony T; Kupper, Marius D; Neal, Daniel; Nabilsi, Nancy H; Kladde, Michael P; Suslov, Oleg; Brabletz, Simone; Brabletz, Thomas; Reynolds, Brent A; Steindler, Dennis A

    2013-01-01

    Glioblastoma remains one of the most lethal types of cancer, and is the most common brain tumour in adults. In particular, tumour recurrence after surgical resection and radiation invariably occurs regardless of aggressive chemotherapy. Here, we provide evidence that the transcription factor ZEB1 (zinc finger E-box binding homeobox 1) exerts simultaneous influence over invasion, chemoresistance and tumourigenesis in glioblastoma. ZEB1 is preferentially expressed in invasive glioblastoma cells, where the ZEB1-miR-200 feedback loop interconnects these processes through the downstream effectors ROBO1, c-MYB and MGMT. Moreover, ZEB1 expression in glioblastoma patients is predictive of shorter survival and poor Temozolomide response. Our findings indicate that this regulator of epithelial-mesenchymal transition orchestrates key features of cancer stem cells in malignant glioma and identify ROBO1, OLIG2, CD133 and MGMT as novel targets of the ZEB1 pathway. Thus, ZEB1 is an important candidate molecule for glioblastoma recurrence, a marker of invasive tumour cells and a potential therapeutic target, along with its downstream effectors. Glioblastoma have a poor prognosis, mainly due to infiltrating and therapy resistant cells leading to cancer recurrence. Here, tumor formation, invasion and resistance are not independent but intertwined processes regulated by the EMT activator ZEB1. PMID:23818228

  14. Integrating Environmental and Socio-Economic Indicators of a Linked Catchment-Coastal System Using Variable Environmental Intensity

    NASA Astrophysics Data System (ADS)

    Dymond, John R.; Davie, Tim J. A.; Fenemor, Andrew D.; Ekanayake, Jagath C.; Knight, Ben R.; Cole, Anthony O.; de Oca Munguia, Oscar Montes; Allen, Will J.; Young, Roger G.; Basher, Les R.; Dresser, Marc; Batstone, Chris J.

    2010-09-01

    Can we develop land use policy that balances the conflicting views of stakeholders in a catchment while moving toward long term sustainability? Adaptive management provides a strategy for this whereby measures of catchment performance are compared against performance goals in order to progressively improve policy. However, the feedback loop of adaptive management is often slow and irreversible impacts may result before policy has been adapted. In contrast, integrated modelling of future land use policy provides rapid feedback and potentially improves the chance of avoiding unwanted collapse events. Replacing measures of catchment performance with modelled catchment performance has usually required the dynamic linking of many models, both biophysical and socio-economic—and this requires much effort in software development. As an alternative, we propose the use of variable environmental intensity (defined as the ratio of environmental impact over economic output) in a loose coupling of models to provide a sufficient level of integration while avoiding significant effort required for software development. This model construct was applied to the Motueka Catchment of New Zealand where several biophysical (riverine water quantity, sediment, E. coli faecal bacteria, trout numbers, nitrogen transport, marine productivity) models, a socio-economic (gross output, gross margin, job numbers) model, and an agent-based model were linked. An extreme set of land use scenarios (historic, present, and intensive) were applied to this modelling framework. Results suggest that the catchment is presently in a near optimal land use configuration that is unlikely to benefit from further intensification. This would quickly put stress on water quantity (at low flow) and water quality ( E. coli). To date, this model evaluation is based on a theoretical test that explores the logical implications of intensification at an unlikely extreme in order to assess the implications of likely growth

  15. Testing pathways linking exposure to community violence and sexual behaviors among African American youth.

    PubMed

    Voisin, Dexter R; Hotton, Anna L; Neilands, Torsten B

    2014-09-01

    Exposure to community violence and HIV sexual risks are two major public health concerns among youth. This study tests various pathways linking exposure to community violence and sexual behaviors among African American adolescents. Using a sample of 563 (61% females) African American youth attending high school we examined whether problematic psychological symptoms, low school engagement, and/or negative perceptions of peer norms about safer sex functioned as pathways linking exposure to community violence and sexual behaviors. Major findings indicated that, for boys, the relationship between exposure to community violence and sexual début and sexual risk behaviors were linked by aggression. In addition, the relationship between exposure to community violence and sexual risk behaviors were linked by negative perceptions of peer attitudes about safer sex. For girls, the relationship between exposure to community violence and sexual début was linked by aggression and negative perceptions of peer attitudes about safer sex. These findings provide support for pathways linking exposure to community violence to sexual behaviors.

  16. Regulation of DNA cross-link repair by the Fanconi anemia/BRCA pathway

    PubMed Central

    Kim, Hyungjin; D'Andrea, Alan D.

    2012-01-01

    The maintenance of genome stability is critical for survival, and its failure is often associated with tumorigenesis. The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand cross-links (ICLs), and a germline defect in the pathway results in FA, a cancer predisposition syndrome driven by genome instability. Central to this pathway is the monoubiquitination of FANCD2, which coordinates multiple DNA repair activities required for the resolution of ICLs. Recent studies have demonstrated how the FA pathway coordinates three critical DNA repair processes, including nucleolytic incision, translesion DNA synthesis (TLS), and homologous recombination (HR). Here, we review recent advances in our understanding of the downstream ICL repair steps initiated by ubiquitin-mediated FA pathway activation. PMID:22751496

  17. The Viability of Combining Academic and Career Pathways: A Study of Linked Learning

    ERIC Educational Resources Information Center

    Hubbard, Lea; McDonald, Mary

    2014-01-01

    In an attempt to reform high schools and prepare students with the knowledge and skills needed for the 21st century, educators and policymakers have turned to programs that combine career and academic pathways. One such program, Linked Learning, has taken up the reform challenge by relying on technical adjustments, rearranging students'…

  18. Linking Strengths: Identifying and Exploring Protective Factor Clusters in Academically Resilient Low-Socioeconomic Urban Students of Color

    ERIC Educational Resources Information Center

    Morales, Erik E.

    2010-01-01

    Based on data from qualitative interviews with 50 high-achieving low-socioeconomic students of color, two "clusters" of important and symbiotic protective factors are identified and explored. Each cluster consists of a series of interrelated protective factors identified by the participants as crucial to their statistically exceptional academic…

  19. Adolescent Work Intensity, School Performance, and Substance Use: Links Vary by Race/Ethnicity and Socioeconomic Status

    ERIC Educational Resources Information Center

    Bachman, Jerald G.; Staff, Jeremy; O'Malley, Patrick M.; Freedman-Doan, Peter

    2013-01-01

    High school students who spend long hours in paid employment during the school year are at increased risk of lower grades and higher substance use, although questions remain about whether these linkages reflect causation or prior differences (selection effects). Questions also remain about whether such associations vary by socioeconomic status…

  20. Axonal Pathways Linked to Therapeutic and Nontherapeutic Outcomes During Psychiatric Deep Brain Stimulation

    PubMed Central

    Lujan, J. Luis; Chaturvedi, Ashutosh; Malone, Donald A.; Rezai, Ali R.; Machado, Andre G.; McIntyre, Cameron C.

    2016-01-01

    Objective The underlying hypothesis of our work is that specific clinical neuropsychiatric benefits can be achieved by selective activation of specific axonal pathways during deep brain stimulation (DBS). As such, the goal of this study was to develop a method for identifying axonal pathways whose activation is most likely necessary for achieving therapeutic benefits during DBS. Experimental design Our approach combined clinical data, diffusion tensor tractography, and computer models of patient-specific neurostimulation to identify particular axonal pathways activated by DBS and determine their correlations with individual clinical outcome measures. We used this method to evaluate a cohort of seven treatment-resistant depression patients treated with DBS of the ventral anterior internal capsule and ventral striatum (VC/VS). Principal observations Clinical responders exhibited five axonal pathways that were consistently activated by DBS. All five pathways coursed lateral and medial to the VS or dorsal and lateral to the nucleus accumbens; however, details of their specific trajectories differed. Similarly, one common pathway was identified across nonresponders. Conclusions Our method and preliminary results provide important background for studies aiming to expand scientific characterization of neural circuitry associated with specific psychiatric outcomes from DBS. Furthermore, identification of pathways linked to therapeutic benefit provides opportunities to improve clinical selection of surgical targets and stimulation settings for DBS devices. PMID:21520343

  1. Seeing the destination but not the path: Effects of socioeconomic disadvantage on school-focused possible self content and linked behavioral strategies.

    PubMed

    Oyserman, Daphna; Johnson, Elizabeth; James, Leah

    2011-10-01

    Low-income children perform better in school when school-focused future identities are a salient aspect of their possible self for the coming year and these school-focused future identities are linked to behavioral strategies (Oyserman et al., 2006). Hierarchical linear modeling of data from a four-state low-income neighborhood sample of eighth-graders suggests two central consequences of family and neighborhood socioeconomic deprivation on children's school-focused possible identities and strategies. First, higher neighborhood disadvantage is associated with greater salience of school in children's possible self for the coming year. Second, disadvantage clouds the path to school-success; controlling for salience of school-focused possible identities, children living in lower socioeconomic status families and boys living in more economically disadvantaged neighborhoods were less likely to have strategies to attain their school-focused possible identities. The influence of family socioeconomic status was seen particularly with regard to strategies to attain academic success and teacher engagement aspects of school-focused identities.

  2. How could differences in 'control over destiny' lead to socio-economic inequalities in health? A synthesis of theories and pathways in the living environment.

    PubMed

    Whitehead, Margaret; Pennington, Andy; Orton, Lois; Nayak, Shilpa; Petticrew, Mark; Sowden, Amanda; White, Martin

    2016-05-01

    We conducted the first synthesis of theories on causal associations and pathways connecting degree of control in the living environment to socio-economic inequalities in health-related outcomes. We identified the main theories about how differences in 'control over destiny' could lead to socio-economic inequalities in health, and conceptualised these at three distinct explanatory levels: micro/personal; meso/community; and macro/societal. These levels are interrelated but have rarely been considered together in the disparate literatures in which they are located. This synthesis of theories provides new conceptual frameworks to contribute to the design and conduct of theory-led evaluations of actions to tackle inequalities in health.

  3. A biological pathway linking inflammation and depression: activation of indoleamine 2,3-dioxygenase.

    PubMed

    Christmas, David M; Potokar, Jp; Davies, Simon Jc

    2011-01-01

    This article highlights the evidence linking depression to increased inflammatory drive and explores putative mechanisms for the association by reviewing both preclinical and clinical literature. The enzyme indoleamine 2,3-dioxygenase is induced by proinflammatory cytokines and may form a link between immune functioning and altered neurotransmission, which results in depression. Increased indoleamine 2,3-dioxygenase activity may cause both tryptophan depletion and increased neurotoxic metabolites of the kynurenine pathway, two alterations which have been hypothesized to cause depression. The tryptophan-kynurenine pathway is comprehensively described with a focus on the evidence linking metabolite alterations to depression. The use of immune-activated groups at high risk of depression have been used to explore these hypotheses; we focus on the studies involving chronic hepatitis C patients receiving interferon-alpha, an immune activating cytokine. Findings from this work have led to novel strategies for the future development of antidepressants including inhibition of indoleamine 2,3-dioxygenase, moderating the cytokines which activate it, or addressing other targets in the kynurenine pathway.

  4. City-Specific Spatiotemporal Infant and Neonatal Mortality Clusters: Links with Socioeconomic and Air Pollution Spatial Patterns in France.

    PubMed

    Padilla, Cindy M; Kihal-Talantikit, Wahida; Vieira, Verónica M; Deguen, Séverine

    2016-01-01

    Infant and neonatal mortality indicators are known to vary geographically, possibly as a result of socioeconomic and environmental inequalities. To better understand how these factors contribute to spatial and temporal patterns, we conducted a French ecological study comparing two time periods between 2002 and 2009 for three (purposefully distinct) Metropolitan Areas (MAs) and the city of Paris, using the French census block of parental residence as the geographic unit of analysis. We identified areas of excess risk and assessed the role of neighborhood deprivation and average nitrogen dioxide concentrations using generalized additive models to generate maps smoothed on longitude and latitude. Comparison of the two time periods indicated that statistically significant areas of elevated infant and neonatal mortality shifted northwards for the city of Paris, are present only in the earlier time period for Lille MA, only in the later time period for Lyon MA, and decrease over time for Marseille MA. These city-specific geographic patterns in neonatal and infant mortality are largely explained by socioeconomic and environmental inequalities. Spatial analysis can be a useful tool for understanding how risk factors contribute to disparities in health outcomes ranging from infant mortality to infectious disease-a leading cause of infant mortality. PMID:27338439

  5. City-Specific Spatiotemporal Infant and Neonatal Mortality Clusters: Links with Socioeconomic and Air Pollution Spatial Patterns in France

    PubMed Central

    Padilla, Cindy M.; Kihal-Talantikit, Wahida; Vieira, Verónica M.; Deguen, Séverine

    2016-01-01

    Infant and neonatal mortality indicators are known to vary geographically, possibly as a result of socioeconomic and environmental inequalities. To better understand how these factors contribute to spatial and temporal patterns, we conducted a French ecological study comparing two time periods between 2002 and 2009 for three (purposefully distinct) Metropolitan Areas (MAs) and the city of Paris, using the French census block of parental residence as the geographic unit of analysis. We identified areas of excess risk and assessed the role of neighborhood deprivation and average nitrogen dioxide concentrations using generalized additive models to generate maps smoothed on longitude and latitude. Comparison of the two time periods indicated that statistically significant areas of elevated infant and neonatal mortality shifted northwards for the city of Paris, are present only in the earlier time period for Lille MA, only in the later time period for Lyon MA, and decrease over time for Marseille MA. These city-specific geographic patterns in neonatal and infant mortality are largely explained by socioeconomic and environmental inequalities. Spatial analysis can be a useful tool for understanding how risk factors contribute to disparities in health outcomes ranging from infant mortality to infectious disease—a leading cause of infant mortality. PMID:27338439

  6. City-Specific Spatiotemporal Infant and Neonatal Mortality Clusters: Links with Socioeconomic and Air Pollution Spatial Patterns in France.

    PubMed

    Padilla, Cindy M; Kihal-Talantikit, Wahida; Vieira, Verónica M; Deguen, Séverine

    2016-01-01

    Infant and neonatal mortality indicators are known to vary geographically, possibly as a result of socioeconomic and environmental inequalities. To better understand how these factors contribute to spatial and temporal patterns, we conducted a French ecological study comparing two time periods between 2002 and 2009 for three (purposefully distinct) Metropolitan Areas (MAs) and the city of Paris, using the French census block of parental residence as the geographic unit of analysis. We identified areas of excess risk and assessed the role of neighborhood deprivation and average nitrogen dioxide concentrations using generalized additive models to generate maps smoothed on longitude and latitude. Comparison of the two time periods indicated that statistically significant areas of elevated infant and neonatal mortality shifted northwards for the city of Paris, are present only in the earlier time period for Lille MA, only in the later time period for Lyon MA, and decrease over time for Marseille MA. These city-specific geographic patterns in neonatal and infant mortality are largely explained by socioeconomic and environmental inequalities. Spatial analysis can be a useful tool for understanding how risk factors contribute to disparities in health outcomes ranging from infant mortality to infectious disease-a leading cause of infant mortality.

  7. Socioeconomic Context and Emotional-Behavioral Achievement Links: Concurrent and Prospective Associations Among Low- and High-Income Youth

    PubMed Central

    Ansary, Nadia S.; McMahon, Thomas J.; Luthar, Suniya S.

    2012-01-01

    Temporal associations in the relationship between emotional-behavioral difficulty and academic achievement were explored in 2 samples followed from 6th through 8th grade. The first sample comprised 280 students entering an economically disadvantaged urban middle school and the second comprised 318 students entering an affluent suburban middle school. Among disadvantaged youth, emotional indices were concurrently associated with poorer achievement while prospective associations between substance use and achievement were evident. For privileged adolescents, only a significant concurrent relationship emerged between social anxiety and achievement, although nonsignificant trends in the data suggest other, albeit weak, associations. The findings are discussed in terms of similarities and differences in these temporal associations across 2 samples representing extremes of the socioeconomic continuum. PMID:23129975

  8. Functional characterization of Sporothrix schenckii glycosidases involved in the N-linked glycosylation pathway.

    PubMed

    Lopes-Bezerra, Leila M; Lozoya-Pérez, Nancy E; López-Ramírez, Luz A; Martínez-Álvarez, José A; Teixeira, Marcus M; Felipe, Maria S S; Flores-Carreón, Arturo; Mora-Montes, Héctor M

    2015-01-01

    Protein glycosylation pathways are conserved metabolic processes in eukaryotic organisms and are required for cell fitness. In fungal pathogens, the N-linked glycosylation pathway is indispensable for proper cell wall composition and virulence. In Sporothrix schenckii sensu stricto, the causative agent of sporotrichosis, little is known about this glycosylation pathway. Here, using a genome-wide screening for putative members of the glycosyl hydrolase (CAZy - GH) families 47 and 63, which group enzymes involved in the processing step during N-linked glycan maturation, we found seven homologue genes belonging to family 47 and one to family 63. The eight genes were individually expressed in C. albicans null mutants lacking either MNS1 (for members of family 47) or CWH41 (for the member of family 63). Our results indicate that SsCWH41 is the functional ortholog of CaCWH41, whereas SsMNS1 is the functional ortholog of CaMNS1. The remaining genes of family 47 encode Golgi mannosidases and endoplasmic reticulum degradation-enhancing alpha-mannosidase-like proteins (EDEMs). Since these GH families gather proteins used as target for drugs to control cell growth, identification of these genes could help in the design of antifungals that could be used to treat sporotrichosis and other fungal diseases. In addition, to our knowledge, we are the first to report that Golgi mannosidases and EDEMs are expressed and characterized in yeast cells.

  9. Functional characterization of Sporothrix schenckii glycosidases involved in the N-linked glycosylation pathway.

    PubMed

    Lopes-Bezerra, Leila M; Lozoya-Pérez, Nancy E; López-Ramírez, Luz A; Martínez-Álvarez, José A; Teixeira, Marcus M; Felipe, Maria S S; Flores-Carreón, Arturo; Mora-Montes, Héctor M

    2015-01-01

    Protein glycosylation pathways are conserved metabolic processes in eukaryotic organisms and are required for cell fitness. In fungal pathogens, the N-linked glycosylation pathway is indispensable for proper cell wall composition and virulence. In Sporothrix schenckii sensu stricto, the causative agent of sporotrichosis, little is known about this glycosylation pathway. Here, using a genome-wide screening for putative members of the glycosyl hydrolase (CAZy - GH) families 47 and 63, which group enzymes involved in the processing step during N-linked glycan maturation, we found seven homologue genes belonging to family 47 and one to family 63. The eight genes were individually expressed in C. albicans null mutants lacking either MNS1 (for members of family 47) or CWH41 (for the member of family 63). Our results indicate that SsCWH41 is the functional ortholog of CaCWH41, whereas SsMNS1 is the functional ortholog of CaMNS1. The remaining genes of family 47 encode Golgi mannosidases and endoplasmic reticulum degradation-enhancing alpha-mannosidase-like proteins (EDEMs). Since these GH families gather proteins used as target for drugs to control cell growth, identification of these genes could help in the design of antifungals that could be used to treat sporotrichosis and other fungal diseases. In addition, to our knowledge, we are the first to report that Golgi mannosidases and EDEMs are expressed and characterized in yeast cells. PMID:25526779

  10. The Role of Parenting in Linking Family Socioeconomic Disadvantage to Physical Activity in Adolescence and Young Adulthood

    ERIC Educational Resources Information Center

    Lee, Hedwig

    2014-01-01

    Parents play an important role in influencing adolescent health behaviors and parenting practices may be an important pathway through which social disadvantage influences adolescent health behaviors that can persist into adulthood. This analysis uses the National Longitudinal Study of Adolescent Health to examine how parenting practices mediate…

  11. Planarian Hh signaling regulates regeneration polarity and links Hh pathway evolution to cilia

    PubMed Central

    Rink, Jochen C.; Gurley, Kyle A.; Elliott, Sarah A.; Alvarado, Alejandro Sánchez

    2010-01-01

    The Hedgehog (Hh) signaling pathway plays multiple essential roles during metazoan development, homeostasis, and disease. Although core protein components are highly conserved, the variations in Hh signal transduction mechanisms exhibited by existing model systems (Drosophila, fish, and mammals) are difficult to understand. We characterize the Hh pathway in planarians. Hh signaling is essential for establishing the Anterior/Posterior axis during regeneration by modulating wnt expression. Moreover, RNAi methods to reduce signal transduction proteins Cos2/Kif27/Kif7, Fused, or Iguana do not result in detectable Hh signaling defects; however, these proteins are essential for planarian ciliogenesis. Our study expands the understanding of Hh signaling in the animal kingdom and suggests an ancestral mechanistic link between Hh signaling and the function of cilia. PMID:19933103

  12. A spatial analysis of variations in health access: linking geography, socio-economic status and access perceptions

    PubMed Central

    2011-01-01

    Background This paper analyses the relationship between public perceptions of access to general practitioners (GPs) surgeries and hospitals against health status, car ownership and geographic distance. In so doing it explores the different dimensions associated with facility access and accessibility. Methods Data on difficulties experienced in accessing health services, respondent health status and car ownership were collected through an attitudes survey. Road distances to the nearest service were calculated for each respondent using a GIS. Difficulty was related to geographic distance, health status and car ownership using logistic generalized linear models. A Geographically Weighted Regression (GWR) was used to explore the spatial non-stationarity in the results. Results Respondent long term illness, reported bad health and non-car ownership were found to be significant predictors of difficulty in accessing GPs and hospitals. Geographic distance was not a significant predictor of difficulty in accessing hospitals but was for GPs. GWR identified the spatial (local) variation in these global relationships indicating locations where the predictive strength of the independent variables was higher or lower than the global trend. The impacts of bad health and non-car ownership on the difficulties experienced in accessing health services varied spatially across the study area, whilst the impacts of geographic distance did not. Conclusions Difficulty in accessing different health facilities was found to be significantly related to health status and car ownership, whilst the impact of geographic distance depends on the service in question. GWR showed how these relationships were varied across the study area. This study demonstrates that the notion of access is a multi-dimensional concept, whose composition varies with location, according to the facility being considered and the health and socio-economic status of the individual concerned. PMID:21787394

  13. Dominant Enhancers of Egfr in Drosophila Melanogaster: Genetic Links between the Notch and Egfr Signaling Pathways

    PubMed Central

    Price, J. V.; Savenye, E. D.; Lum, D.; Breitkreutz, A.

    1997-01-01

    The Drosophila epidermal growth factor receptor (EGFR) is a key component of a complex signaling pathway that participates in multiple developmental processes. We have performed an F(1) screen for mutations that cause dominant enhancement of wing vein phenotypes associated with mutations in Egfr. With this screen, we have recovered mutations in Hairless (H), vein, groucho (gro), and three apparently novel loci. All of the E(Egfr)s we have identified show dominant interactions in transheterozygous combinations with each other and with alleles of N or Su(H), suggesting that they are involved in cross-talk between the N and EGFR signaling pathways. Further examination of the phenotypic interactions between Egfr, H, and gro revealed that reductions in Egfr activity enhanced both the bristle loss associated with H mutations, and the bristle hyperplasia and ocellar hypertrophy associated with gro mutations. Double mutant combinations of Egfr and gro hypomorphic alleles led to the formation of ectopic compound eyes in a dosage sensitive manner. Our findings suggest that these E(Egfr)s represent links between the Egfr and Notch signaling pathways, and that Egfr activity can either promote or suppress Notch signaling, depending on its developmental context. PMID:9383058

  14. The TEA transcription factor Tec1 links TOR and MAPK pathways to coordinate yeast development.

    PubMed

    Brückner, Stefan; Kern, Sandra; Birke, Raphael; Saugar, Irene; Ulrich, Helle D; Mösch, Hans-Ulrich

    2011-10-01

    In Saccharomyces cerevisiae, the TEA transcription factor Tec1 controls several developmental programs in response to nutrients and pheromones. Tec1 is targeted by the pheromone-responsive Fus3/Kss1 mitogen-activated protein kinase (MAPK) cascade, which destabilizes the transcription factor to ensure efficient mating of sexual partner cells. The regulation of Tec1 by signaling pathways that control cell division and development in response to nutrients, however, is not known. Here, we show that Tec1 protein stability is under control of the nutrient-sensitive target of rapamycin complex 1 (TORC1) signaling pathway via the Tip41-Tap42-Sit4 branch. We further show that degradation of Tec1 upon inhibition of TORC1 by rapamycin does not involve polyubiquitylation and appears to be proteasome independent. However, rapamycin-induced Tec1 degradation depends on the HECT ubiquitin ligase Rsp5, which physically interacts with Tec1 via conserved PxY motives. We further demonstrate that rapamycin and mating pheromone control Tec1 protein stability through distinct mechanisms by targeting different domains of the transcription factor. Finally, we show that Tec1 is a positive regulator of yeast chronological lifespan (CLS), a known TORC1-regulated process. Our findings indicate that in yeast, Tec1 links TORC1 and MAPK signaling pathways to coordinate control of cellular development in response to different stimuli. PMID:21840851

  15. High CO2 Primes Plant Biotic Stress Defences through Redox-Linked Pathways1[OPEN

    PubMed Central

    2016-01-01

    Industrial activities have caused tropospheric CO2 concentrations to increase over the last two centuries, a trend that is predicted to continue for at least the next several decades. Here, we report that growth of plants in a CO2-enriched environment activates responses that are central to defense against pathogenic attack. Salicylic acid accumulation was triggered by high-growth CO2 in Arabidopsis (Arabidopsis thaliana) and other plants such as bean (Phaseolus vulgaris). A detailed analysis in Arabidopsis revealed that elevated CO2 primes multiple defense pathways, leading to increased resistance to bacterial and fungal challenge. Analysis of gene-specific mutants provided no evidence that activation of plant defense pathways by high CO2 was caused by stomatal closure. Rather, the activation is partly linked to metabolic effects involving redox signaling. In support of this, genetic modification of redox components (glutathione contents and NADPH-generating enzymes) prevents full priming of the salicylic acid pathway and associated resistance by high CO2. The data point to a particularly influential role for the nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase, a cytosolic enzyme whose role in plants remains unclear. Our observations add new information on relationships between high CO2 and oxidative signaling and provide novel insight into plant stress responses in conditions of increased CO2. PMID:27578552

  16. Intracellular pathways linking hypoxia to activation of c-fos and AP-1.

    PubMed

    Premkumar, D R; Adhikary, G; Overholt, J L; Simonson, M S; Cherniack, N S; Prabhakar, N R

    2000-01-01

    Organisms respond to hypoxia through detection of blood oxygen levels by sensors at peripheral chemoreceptors and by receptors in certain key cells of the body. The pathways over which peripheral chemoreceptor signals are transmitted to respiratory muscles are well established. However, the intracellular pathways that transmit hypoxic stimulus to gene activation are just being identified. Using anti-sense c-fos strategy, we have shown that c-fos is essential for the activation of activator protein-1 transcription factor complex (AP-1) and subsequent stimulation of downstream genes such as tyrosine hydroxylase (TH; Mishra et al. 1998). The purpose of the present study was to identify intracellular pathways that link hypoxia to activation of c-fos. The results of the present study show that hypoxia causes Ca2+ influx through L-type voltage gated Ca2+ channels and that hypoxia-induced c-fos gene expression is Ca2+/calmodulin dependent. We also demonstrate that hypoxia activates the extracellular-regulated kinase (ERK) and p38, but not JNK. Further, phosphorylation of ERK is essential for c-fos activation via SRE cis-element. Further characterization of nuclear signalling pathways provides evidence for the involvement of Src, a non receptor protein tyrosine kinase, and Ras, a small G protein, in the hypoxia-induced c-fos gene expression. These results suggest a possible role for non-receptor protein tyrosine kinases in propagating signals from G-protein coupled receptors to the activation of immediate early genes such as c-fos during hypoxia.

  17. Linking the Fragile X mental retardation protein to the lipoxygenase pathway.

    PubMed

    Beaulieu, Marc-Alexandre

    2013-03-01

    Fragile X mental retardation is caused by the absence of the FMRP (fragile X mental retardation protein) a RNA-binding protein encoded by the Fmr1 gene. Despite the large number of studies about this syndrome, it is still unclear how the absence of FMRP affects the physiology of the nervous system. It has been reported however that the brain of the Fmr1-KO mouse shows altered membrane protein and lipid oxidation. There is also indirect evidence that FMRP may be involved in a negative feedback mechanism with metabotropic glutamate receptors (mGluRs). In this article, we will discuss several lines of evidences which tend to prove that the lipoxygenase pathway might be the missing link between FMRP and mGluRs.

  18. The Genetic Link between Parkinson's Disease and the Kynurenine Pathway Is Still Missing.

    PubMed

    Török, Nóra; Török, Rita; Szolnoki, Zoltán; Somogyvári, Ferenc; Klivényi, Péter; Vécsei, László

    2015-01-01

    Background. There is substantial evidence that the kynurenine pathway (KP) plays a role in the normal physiology of the brain and is involved in the pathology of neurodegenerative disorders such as Huntington's disease and Parkinson's disease (PD). Objective. We set out to investigate the potential roles in PD of single nucleotide polymorphisms (SNPs) from one of the key enzymes of the KP, kynurenine 3-monooxygenase (KMO). Methods. 105 unrelated, clinically definitive PD patients and 131 healthy controls were enrolled to investigate the possible effects of the different alleles of KMO. Fluorescently labeled TaqMan probes were used for allele discrimination. Results. None of the four investigated SNPs proved to be associated with PD or influenced the age at onset of the disease. Conclusions. The genetic link between the KP and PD is still missing. The investigated SNPs presumably do not appear to influence the function of KMO and probably do not contain binding sites for regulatory proteins of relevance in PD. This is the first study to assess the genetic background behind the biochemical alterations of the kynurenine pathway in PD, directing the attention to this previously unexamined field.

  19. A cortical-subcortical syntax pathway linking Broca's area and the striatum.

    PubMed

    Teichmann, Marc; Rosso, Charlotte; Martini, Jean-Baptiste; Bloch, Isabelle; Brugières, Pierre; Duffau, Hugues; Lehéricy, Stéphane; Bachoud-Lévi, Anne-Catherine

    2015-06-01

    Combinatorial syntax has been shown to be underpinned by cortical key regions such as Broca's area and temporal cortices, and by subcortical structures such as the striatum. The cortical regions are connected via several cortico-to-cortical tracts impacting syntactic processing (e.g., the arcuate) but it remains unclear whether and how the striatum can be integrated into this cortex-centered syntax network. Here, we used a systematic stepwise approach to investigate the existence and syntactic function of an additional deep Broca-striatum pathway. We first asked 15 healthy controls and 12 patients with frontal/striatal lesions to perform three syntax tests. The results obtained were subjected to voxel-based lesion-symptom mapping (VLSM) to provide an anatomo-functional approximation of the pathway. The significant VLSM clusters were then overlapped with the probability maps of four cortico-cortical language tracts generated for 12 healthy participants (arcuate, extreme capsule fiber system, uncinate, aslant), including a probabilistic Broca-striatum tract. Finally, we carried out quantitative analyses of the relationship between the lesion load along the tracts and syntactic processing, by calculating tract-lesion overlap for each patient and analyzing the correlation with syntactic data. Our findings revealed a Broca-striatum tract linking BA45 with the left caudate head and overlapping with VLSM voxel clusters relating to complex syntax. The lesion load values for this tract were correlated with complex syntax scores, whereas no such correlation was observed for the other tracts. These results extend current syntax-network models, by adding a deep "Broca-caudate pathway," and are consistent with functional accounts of frontostriatal circuits. PMID:25682763

  20. A cortical-subcortical syntax pathway linking Broca's area and the striatum.

    PubMed

    Teichmann, Marc; Rosso, Charlotte; Martini, Jean-Baptiste; Bloch, Isabelle; Brugières, Pierre; Duffau, Hugues; Lehéricy, Stéphane; Bachoud-Lévi, Anne-Catherine

    2015-06-01

    Combinatorial syntax has been shown to be underpinned by cortical key regions such as Broca's area and temporal cortices, and by subcortical structures such as the striatum. The cortical regions are connected via several cortico-to-cortical tracts impacting syntactic processing (e.g., the arcuate) but it remains unclear whether and how the striatum can be integrated into this cortex-centered syntax network. Here, we used a systematic stepwise approach to investigate the existence and syntactic function of an additional deep Broca-striatum pathway. We first asked 15 healthy controls and 12 patients with frontal/striatal lesions to perform three syntax tests. The results obtained were subjected to voxel-based lesion-symptom mapping (VLSM) to provide an anatomo-functional approximation of the pathway. The significant VLSM clusters were then overlapped with the probability maps of four cortico-cortical language tracts generated for 12 healthy participants (arcuate, extreme capsule fiber system, uncinate, aslant), including a probabilistic Broca-striatum tract. Finally, we carried out quantitative analyses of the relationship between the lesion load along the tracts and syntactic processing, by calculating tract-lesion overlap for each patient and analyzing the correlation with syntactic data. Our findings revealed a Broca-striatum tract linking BA45 with the left caudate head and overlapping with VLSM voxel clusters relating to complex syntax. The lesion load values for this tract were correlated with complex syntax scores, whereas no such correlation was observed for the other tracts. These results extend current syntax-network models, by adding a deep "Broca-caudate pathway," and are consistent with functional accounts of frontostriatal circuits.

  1. Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson's disease.

    PubMed

    Duke, D C; Moran, L B; Kalaitzakis, M E; Deprez, M; Dexter, D T; Pearce, R K B; Graeber, M B

    2006-07-01

    There is growing evidence that dysfunction of the mitochondrial respiratory chain and failure of the cellular protein degradation machinery, specifically the ubiquitin-proteasome system, play an important role in the pathogenesis of Parkinson's disease. We now show that the corresponding pathways of these two systems are linked at the transcriptomic level in Parkinsonian substantia nigra. We examined gene expression in medial and lateral substantia nigra (SN) as well as in frontal cortex using whole genome DNA oligonucleotide microarrays. In this study, we use a hypothesis-driven approach in analysing microarray data to describe the expression of mitochondrial and ubiquitin-proteasomal system (UPS) genes in Parkinson's disease (PD). Although a number of genes showed up-regulation, we found an overall decrease in expression affecting the majority of mitochondrial and UPS sequences. The down-regulated genes include genes that encode subunits of complex I and the Parkinson's-disease-linked UCHL1. The observed changes in expression were very similar for both medial and lateral SN and also affected the PD cerebral cortex. As revealed by "gene shaving" clustering analysis, there was a very significant correlation between the transcriptomic profiles of both systems including in control brains. Therefore, the mitochondria and the proteasome form a higher-order gene regulatory network that is severely perturbed in Parkinson's disease. Our quantitative results also suggest that Parkinson's disease is a disease of more than one cell class, i.e. that it goes beyond the catecholaminergic neuron and involves glia as well.

  2. Pathways linking drug use and labour market trajectories: the role of catastrophic events.

    PubMed

    Richardson, Lindsey; Small, Will; Kerr, Thomas

    2016-01-01

    People affected by substance use disorders often experience sub-optimal employment outcomes. The role of drug use in processes that produce and entrench labour market precarity among people who inject drugs (PWID) have not, however, been fully described. We recruited 22 PWID from ongoing prospective cohort studies in Vancouver, Canada, with whom we conducted semi-structured retrospective interviews and then employed a thematic analysis that drew on concepts from life course theory to explore the mechanisms and pathways linking drug use and labour market trajectories. The participants' narratives identified processes corresponding to causation, whereby suboptimal employment outcomes led to harmful drug use; direct selection, where impairment, health complications or drug-seeking activities selected individuals out of employment; and indirect selection, where external factors, such as catastrophic events, marked the initiation or intensification of substance use concurrent with sudden changes in capacities for employment. Catastrophic events linking negative transitions in both drug use and labour market trajectories were of primary importance, demarcating critical initiation and transitional events in individual risk trajectories. These results challenge conventional assumptions about the primacy of drug use in determining employment outcomes among PWID and suggest the importance of multidimensional support to mitigate the initiation, accumulation and entrenchment of labour market and drug-related disadvantage.

  3. Identification of genes involved in the biosynthesis and attachment of Methanococcus voltae N-linked glycans: insight into N-linked glycosylation pathways in Archaea.

    PubMed

    Chaban, Bonnie; Voisin, Sebastien; Kelly, John; Logan, Susan M; Jarrell, Ken F

    2006-07-01

    N-linked glycosylation is recognized as an important post-translational modification across all three domains of life. However, the understanding of the genetic pathways for the assembly and attachment of N-linked glycans in eukaryotic and bacterial systems far outweighs the knowledge of comparable processes in Archaea. The recent characterization of a novel trisaccharide [beta-ManpNAcA6Thr-(1-4)-beta-GlcpNAc3NAcA-(1-3)-beta-GlcpNAc]N-linked to asparagine residues in Methanococcus voltae flagellin and S-layer proteins affords new opportunities to investigate N-linked glycosylation pathways in Archaea. In this contribution, the insertional inactivation of several candidate genes within the M. voltae genome and their resulting effects on flagellin and S-layer glycosylation are reported. Two of the candidate genes were shown to have effects on flagellin and S-layer protein molecular mass and N-linked glycan structure. Further examination revealed inactivation of either of these two genes also had effects on flagella assembly. These genes, designated agl (archaeal glycosylation) genes, include a glycosyl transferase (aglA) involved in the attachment of the terminal sugar to the glycan and an STT3 oligosaccharyl transferase homologue (aglB) involved in the transfer of the complete glycan to the flagellin and S-layer proteins. These findings document the first experimental evidence for genes involved in any glycosylation process within the domain Archaea. PMID:16824110

  4. Neurocognitive development in socioeconomic context: Multiple mechanisms and implications for measuring socioeconomic status.

    PubMed

    Ursache, Alexandra; Noble, Kimberly G

    2016-01-01

    Socioeconomic status (SES) has been linked to functioning across a variety of neurocognitive domains including language, memory, executive functioning, and social-emotional processing. We review these findings and discuss the ways in which socioeconomic context may shape neural processes such that these skills are supported by different neurobiological pathways in children from lower versus higher SES backgrounds. Moreover, we consider the mechanisms by which SES may be related to specific neurocognitive functions. Specifically, we focus on linguistic exposure and stress as two main pathways through which SES could influence neurocognitive processes and shape relations between the neural and behavioral levels of functioning. Finally, suggestions for conceptualizing and measuring SES in future work are offered. PMID:26681619

  5. The alexithymic brain: the neural pathways linking alexithymia to physical disorders

    PubMed Central

    2013-01-01

    Alexithymia is a personality trait characterized by difficulties in identifying and describing feelings and is associated with psychiatric and psychosomatic disorders. The mechanisms underlying the link between emotional dysregulation and psychosomatic disorders are unclear. Recent progress in neuroimaging has provided important information regarding emotional experience in alexithymia. We have conducted three brain imaging studies on alexithymia, which we describe herein. This article considers the role of emotion in the development of physical symptoms and discusses a possible pathway that we have identified in our neuroimaging studies linking alexithymia with psychosomatic disorders. In terms of socio-affective processing, alexithymics demonstrate lower reactivity in brain regions associated with emotion. Many studies have reported reduced activation in limbic areas (e.g., cingulate cortex, anterior insula, amygdala) and the prefrontal cortex when alexithymics attempt to feel other people’s feelings or retrieve their own emotional episodes, compared to nonalexithymics. With respect to primitive emotional reactions such as the response to pain, alexithymics show amplified activity in areas considered to be involved in physical sensation. In addition to greater hormonal arousal responses in alexithymics during visceral pain, increased activity has been reported in the insula, anterior cingulate cortex, and midbrain. Moreover, in complex social situations, alexithymics may not be able to use feelings to guide their behavior appropriately. The Iowa gambling task (IGT) was developed to assess decision-making processes based on emotion-guided evaluation. When alexithymics perform the IGT, they fail to learn an advantageous decision-making strategy and show reduced activity in the medial prefrontal cortex, a key area for successful performance of the IGT, and increased activity in the caudate, a region associated with impulsive choice. The neural machinery in

  6. Links between topography, moisture fluxes pathways and precipitation over South America

    NASA Astrophysics Data System (ADS)

    Saurral, Ramiro Ignacio; Camilloni, Inés Angela; Ambrizzi, Tércio

    2014-08-01

    The Andes Cordillera plays a role in driving moisture and heat from tropical onto subtropical South America. It forces the development of a lee-side trough that covers most of western Argentina and a low-level jet that maximizes over Paraguay, eastern Bolivia and northern Argentina and is tightly linked to precipitation variability over much of central and southeastern South America. Its steep slopes and the large zonal gradients in topography between the Equator and 40°S are misrepresented in climate simulations using Global Climate Models (GCM) with resolutions coarser than about 100 km, since they naturally have a poor representation of the Andes and related circulation features. This paper analyses the impact of varying artificially the altitude of the Andes Cordillera in a GCM as well as increasing the horizontal resolution to study how these variations determine moisture fluxes and precipitation over selected regions of South America. Results show that the height of the Andes is crucial in shaping moisture fluxes pathways onto subtropical South America all year long. In particular, the low-level jet is only simulated when the Andes heights are doubled. At the same time, the relationship between the Andes shape and the location of the Bolivian High in summer is also discussed. In terms of precipitation, the lowest bias in the simulations is achieved when the horizontal resolution is increased, while in particular near the Andes foothills the simulated annual rainfall is largely determined by the Mountains shape.

  7. Links between topography, moisture fluxes pathways and precipitation over South America

    NASA Astrophysics Data System (ADS)

    Saurral, Ramiro Ignacio; Camilloni, Inés Angela; Ambrizzi, Tércio

    2015-08-01

    The Andes Cordillera plays a role in driving moisture and heat from tropical onto subtropical South America. It forces the development of a lee-side trough that covers most of western Argentina and a low-level jet that maximizes over Paraguay, eastern Bolivia and northern Argentina and is tightly linked to precipitation variability over much of central and southeastern South America. Its steep slopes and the large zonal gradients in topography between the Equator and 40°S are misrepresented in climate simulations using Global Climate Models (GCM) with resolutions coarser than about 100 km, since they naturally have a poor representation of the Andes and related circulation features. This paper analyses the impact of varying artificially the altitude of the Andes Cordillera in a GCM as well as increasing the horizontal resolution to study how these variations determine moisture fluxes and precipitation over selected regions of South America. Results show that the height of the Andes is crucial in shaping moisture fluxes pathways onto subtropical South America all year long. In particular, the low-level jet is only simulated when the Andes heights are doubled. At the same time, the relationship between the Andes shape and the location of the Bolivian High in summer is also discussed. In terms of precipitation, the lowest bias in the simulations is achieved when the horizontal resolution is increased, while in particular near the Andes foothills the simulated annual rainfall is largely determined by the Mountains shape.

  8. The Vac14-interaction network is linked to regulators of the endolysosomal and autophagic pathway.

    PubMed

    Schulze, Ulf; Vollenbröker, Beate; Braun, Daniela A; Van Le, Truc; Granado, Daniel; Kremerskothen, Joachim; Fränzel, Benjamin; Klosowski, Rafael; Barth, Johannes; Fufezan, Christian; Wolters, Dirk A; Pavenstädt, Hermann; Weide, Thomas

    2014-06-01

    The scaffold protein Vac14 acts in a complex with the lipid kinase PIKfyve and its counteracting phosphatase FIG4, regulating the interconversion of phosphatidylinositol-3-phosphate to phosphatidylinositol-3,5-bisphosphate. Dysfunctional Vac14 mutants, a deficiency of one of the Vac14 complex components, or inhibition of PIKfyve enzymatic activity results in the formation of large vacuoles in cells. How these vacuoles are generated and which processes are involved are only poorly understood. Here we show that ectopic overexpression of wild-type Vac14 as well as of the PIKfyve-binding deficient Vac14 L156R mutant causes vacuoles. Vac14-dependent vacuoles and PIKfyve inhibitor-dependent vacuoles resulted in elevated levels of late endosomal, lysosomal, and autophagy-associated proteins. However, only late endosomal marker proteins were bound to the membranes of these enlarged vacuoles. In order to decipher the linkage between the Vac14 complex and regulators of the endolysosomal pathway, a protein affinity approach combined with multidimensional protein identification technology was conducted, and novel molecular links were unraveled. We found and verified the interaction of Rab9 and the Rab7 GAP TBC1D15 with Vac14. The identified Rab-related interaction partners support the theory that the regulation of vesicular transport processes and phosphatidylinositol-modifying enzymes are tightly interconnected.

  9. Pathway analysis supports association of nonsyndromic cryptorchidism with genetic loci linked to cytoskeleton-dependent functions

    PubMed Central

    Barthold, Julia Spencer; Wang, Yanping; Kolon, Thomas F.; Kollin, Claude; Nordenskjöld, Agneta; Olivant Fisher, Alicia; Figueroa, T. Ernesto; BaniHani, Ahmad H.; Hagerty, Jennifer A.; Gonzaléz, Ricardo; Noh, Paul H.; Chiavacci, Rosetta M.; Harden, Kisha R.; Abrams, Debra J.; Kim, Cecilia E.; Li, Jin; Hakonarson, Hakon; Devoto, Marcella

    2015-01-01

    STUDY QUESTION What are the genetic loci that increase susceptibility to nonsyndromic cryptorchidism, or undescended testis? SUMMARY ANSWER A genome-wide association study (GWAS) suggests that susceptibility to cryptorchidism is heterogeneous, with a subset of suggestive signals linked to cytoskeleton-dependent functions and syndromic forms of the disease. WHAT IS KNOWN ALREADY Population studies suggest moderate genetic risk of cryptorchidism and possible maternal and environmental contributions to risk. Previous candidate gene analyses have failed to identify a major associated locus, although variants in insulin-like 3 (INSL3), relaxin/insulin-like family peptide receptor 2 (RXFP2) and other hormonal pathway genes may increase risk in a small percentage of patients. STUDY DESIGN, SIZE, DURATION This is a case–control GWAS of 844 boys with nonsyndromic cryptorchidism and 2718 control subjects without syndromes or genital anomalies, all of European ancestry. PARTICIPANTS/MATERIALS, SETTING, METHODS All boys with cryptorchidism were diagnosed and treated by a pediatric specialist. In the discovery phase, DNA was extracted from tissue or blood samples and genotyping performed using the Illumina HumanHap550 and Human610-Quad (Group 1) or OmniExpress (Group 2) platform. We imputed genotypes genome-wide, and combined single marker association results in meta-analyses for all cases and for secondary subphenotype analyses based on testis position, laterality and age, and defined genome-wide significance as P = 7 × 10−9 to correct for multiple testing. Selected markers were genotyped in an independent replication group of European cases (n = 298) and controls (n = 324). We used several bioinformatics tools to analyze top (P < 10−5) and suggestive (P < 10−3) signals for significant enrichment of signaling pathways, cellular functions and custom gene lists after multiple testing correction. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis, we identified 20

  10. Family support and ease of access link socio-economic status and sports club membership in adolescent girls: a mediation study

    PubMed Central

    2013-01-01

    Background Much research has been conducted into the determinants of physical activity (PA) participation among adolescent girls. However, the more specific question of what are the determinants of particular forms of PA participation, such as the link between participation through a sports club, has not been investigated. Accordingly, the aim of this study was to investigate the relationships between participation in a sports club and socio-economic status (SES), access to facilities, and family and peer support, for female adolescents. Methods A survey of 732 female adolescent school students (521 metropolitan, 211 non-metropolitan; 489 Year 7, 243 Year 11) was conducted. The survey included demographic information (living arrangements, ethnicity indicators, and indicators of SES such as parental education and employment status and locality); access to facilities; and family and peer support (travel, encouragement, watching, praise, joint participation). For each characteristic, sports club participants and non-participants were compared using chi-square tests. Multiple mediation analyses were used to investigate the role of access, family and peer support in the link between SES and sport participation. Results There were significant associations (p<0.05) between sports club participation and: all demographic characteristics; all measures of family and peer support; and access to sport-related facilities. Highest levels of participation were associated with monolingual Australian-born families, with two parents, at least one of whom was well-educated, with both parents employed, and high levels of parental assistance, engagement and support. Participation in club sport among both younger and older adolescent girls was significantly positively associated with the SES of both their neighbourhoods and their households, particularly in metropolitan areas. These associations were most strongly mediated by family support and by access to facilities. Conclusions To

  11. Interrogating causal pathways linking genetic variants, small molecule metabolites, and circulating lipids

    PubMed Central

    2014-01-01

    Background Emerging technologies based on mass spectrometry or nuclear magnetic resonance enable the monitoring of hundreds of small metabolites from tissues or body fluids. Profiling of metabolites can help elucidate causal pathways linking established genetic variants to known disease risk factors such as blood lipid traits. Methods We applied statistical methodology to dissect causal relationships between single nucleotide polymorphisms, metabolite concentrations, and serum lipid traits, focusing on 95 genetic loci reproducibly associated with the four main serum lipids (total-, low-density lipoprotein-, and high-density lipoprotein- cholesterol and triglycerides). The dataset used included 2,973 individuals from two independent population-based cohorts with data for 151 small molecule metabolites and four main serum lipids. Three statistical approaches, namely conditional analysis, Mendelian randomization, and structural equation modeling, were compared to investigate causal relationship at sets of a single nucleotide polymorphism, a metabolite, and a lipid trait associated with one another. Results A subset of three lipid-associated loci (FADS1, GCKR, and LPA) have a statistically significant association with at least one main lipid and one metabolite concentration in our data, defining a total of 38 cross-associated sets of a single nucleotide polymorphism, a metabolite and a lipid trait. Structural equation modeling provided sufficient discrimination to indicate that the association of a single nucleotide polymorphism with a lipid trait was mediated through a metabolite at 15 of the 38 sets, and involving variants at the FADS1 and GCKR loci. Conclusions These data provide a framework for evaluating the causal role of components of the metabolome (or other intermediate factors) in mediating the association between established genetic variants and diseases or traits. PMID:24678845

  12. Defects in the N-linked oligosaccharide biosynthetic pathway in a Trypanosoma brucei glycosylation mutant.

    PubMed

    Acosta-Serrano, Alvaro; O'Rear, Jessica; Quellhorst, George; Lee, Soo Hee; Hwa, Kuo-Yuan; Krag, Sharon S; Englund, Paul T

    2004-04-01

    Concanavalin A (ConA) kills the procyclic (insect) form of Trypanosoma brucei by binding to its major surface glycoprotein, procyclin. We previously isolated a mutant cell line, ConA 1-1, that is less agglutinated and more resistant to ConA killing than are wild-type (WT) cells. Subsequently we found that the ConA resistance phenotype in this mutant is due to the fact that the procyclin either has no N-glycan or has an N-glycan with an altered structure. Here we demonstrate that the alteration in procyclin N-glycosylation correlates with two defects in the N-linked oligosaccharide biosynthetic pathway. First, ConA 1-1 has a defect in activity of polyprenol reductase, an enzyme involved in synthesis of dolichol. Metabolic incorporation of [3H]mevalonate showed that ConA 1-1 synthesizes equal amounts of dolichol and polyprenol, whereas WT cells make predominantly dolichol. Second, we found that ConA 1-1 synthesizes and accumulates an oligosaccharide lipid (OSL) precursor that is smaller in size than that from WT cells. The glycan of OSL in WT cells is apparently Man9GlcNAc2, whereas that from ConA 1-1 is Man7GlcNAc2. The smaller OSL glycan in the ConA 1-1 explains how some procyclin polypeptides bear a Man4GlcNAc2 modified with a terminal N-acetyllactosamine group, which is poorly recognized by ConA.

  13. cAMP-dependent proteolysis of GATA-6 is linked to JNK-signaling pathway

    SciTech Connect

    Ushijima, Hironori; Maeda, Masatomo

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6. Black-Right-Pointing-Pointer Effect of a JNK activator anisomycin on the proteolysis was examined. Black-Right-Pointing-Pointer Anisomycin stimulated the export of nuclear GATA-6 into the cytoplasm. Black-Right-Pointing-Pointer JNK activated the CRM1 mediated nuclear export of GATA-6. Black-Right-Pointing-Pointer JNK further stimulated slowly the degradation of GATA-6 by cytoplasmic proteasomes. -- Abstract: A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6 by proteasomes around its IC50. We further examined the effects of SP600125 on the degradation of GATA-6 in detail, since an activator of JNK (anisomycin) is available. Interestingly, anisomycin immediately stimulated the export of nuclear GATA-6 into the cytoplasm, and then the cytoplasmic content of GATA-6 decreased slowly through degradation by proteasomes. Such an effect of anisomycin was inhibited by SP600125, indicating that the observed phenomenon might be linked to the JNK signaling pathway. The inhibitory effect of SP600125 could not be ascribed to the inhibition of PKA, since phosphorylation of CREB occurred in the presence of dbcAMP and SP600125. The nuclear export of GATA-6 was inhibited by leptomycin B, suggesting that CRM1-mediated export could be activated by anisomycin. Furthermore, it seems likely that the JNK activated by anisomycin may stimulate not only the nuclear export of GATA-6 through CRM1 but also the degradation of GATA-6 by cytoplasmic proteasomes. In contrast, A-kinase might activate only the latter process through JNK.

  14. Deregulated tryptophan-kynurenine pathway is linked to inflammation, oxidative stress, and immune activation pathway in cardiovascular diseases

    PubMed Central

    Wang, Qiongxin; Liu, Danxia; Song, Ping; Zou, Ming-Hui

    2016-01-01

    The kynurenine (Kyn) pathway is the major route for tryptophan (Trp) metabolism, and it contributes to several fundamental biological processes. Trp is constitutively oxidized by tryptophan 2, 3-dioxygenase in liver cells. In other cell types, it is catalyzed by an alternative inducible indoleamine-pyrrole 2, 3-dioxygenase (IDO) under certain pathophysiological conditions, which consequently increases the formation of Kyn metabolites. IDO is up-regulated in response to inflammatory conditions as a novel marker of immune activation in early atherosclerosis. Besides, IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis. In particular, Kyn, 3-hydroxykynurenine, and quinolinic acid are positively associated with inflammation, oxidative stress (SOX), endothelial dysfunction, and carotid artery intima-media thickness values in end-stage renal disease patients. Moreover, IDO is a potential novel contributor to vessel relaxation and metabolism in systemic infections, which is also activated in acute severe heart attacks. The Kyn pathway plays a key role in the increased prevalence of cardiovascular disease by regulating inflammation, SOX, and immune activation. PMID:25961549

  15. Combinatorial high-throughput experimental and bioinformatic approach identifies molecular pathways linked with the sensitivity to anticancer target drugs

    PubMed Central

    Venkova, Larisa; Aliper, Alexander; Suntsova, Maria; Kholodenko, Roman; Shepelin, Denis; Borisov, Nicolas; Malakhova, Galina; Vasilov, Raif; Roumiantsev, Sergey; Zhavoronkov, Alex; Buzdin, Anton

    2015-01-01

    Effective choice of anticancer drugs is important problem of modern medicine. We developed a method termed OncoFinder for the analysis of new type of biomarkers reflecting activation of intracellular signaling and metabolic molecular pathways. These biomarkers may be linked with the sensitivity to anticancer drugs. In this study, we compared the experimental data obtained in our laboratory and in the Genomics of Drug Sensitivity in Cancer (GDS) project for testing response to anticancer drugs and transcriptomes of various human cell lines. The microarray-based profiling of transcriptomes was performed for the cell lines before the addition of drugs to the medium, and experimental growth inhibition curves were built for each drug, featuring characteristic IC50 values. We assayed here four target drugs - Pazopanib, Sorafenib, Sunitinib and Temsirolimus, and 238 different cell lines, of which 11 were profiled in our laboratory and 227 - in GDS project. Using the OncoFinder-processed transcriptomic data on ∼600 molecular pathways, we identified pathways showing significant correlation between pathway activation strength (PAS) and IC50 values for these drugs. Correlations reflect relationships between response to drug and pathway activation features. We intersected the results and found molecular pathways significantly correlated in both our assay and GDS project. For most of these pathways, we generated molecular models of their interaction with known molecular target(s) of the respective drugs. For the first time, our study uncovered mechanisms underlying cancer cell response to drugs at the high-throughput molecular interactomic level. PMID:26317900

  16. Combinatorial high-throughput experimental and bioinformatic approach identifies molecular pathways linked with the sensitivity to anticancer target drugs.

    PubMed

    Venkova, Larisa; Aliper, Alexander; Suntsova, Maria; Kholodenko, Roman; Shepelin, Denis; Borisov, Nicolas; Malakhova, Galina; Vasilov, Raif; Roumiantsev, Sergey; Zhavoronkov, Alex; Buzdin, Anton

    2015-09-29

    Effective choice of anticancer drugs is important problem of modern medicine. We developed a method termed OncoFinder for the analysis of new type of biomarkers reflecting activation of intracellular signaling and metabolic molecular pathways. These biomarkers may be linked with the sensitivity to anticancer drugs. In this study, we compared the experimental data obtained in our laboratory and in the Genomics of Drug Sensitivity in Cancer (GDS) project for testing response to anticancer drugs and transcriptomes of various human cell lines. The microarray-based profiling of transcriptomes was performed for the cell lines before the addition of drugs to the medium, and experimental growth inhibition curves were built for each drug, featuring characteristic IC50 values. We assayed here four target drugs - Pazopanib, Sorafenib, Sunitinib and Temsirolimus, and 238 different cell lines, of which 11 were profiled in our laboratory and 227 - in GDS project. Using the OncoFinder-processed transcriptomic data on ~600 molecular pathways, we identified pathways showing significant correlation between pathway activation strength (PAS) and IC50 values for these drugs. Correlations reflect relationships between response to drug and pathway activation features. We intersected the results and found molecular pathways significantly correlated in both our assay and GDS project. For most of these pathways, we generated molecular models of their interaction with known molecular target(s) of the respective drugs. For the first time, our study uncovered mechanisms underlying cancer cell response to drugs at the high-throughput molecular interactomic level. PMID:26317900

  17. The Association of Attention Deficit Hyperactivity Disorder with Socioeconomic Disadvantage: Alternative Explanations and Evidence

    ERIC Educational Resources Information Center

    Russell, Ginny; Ford, Tamsin; Rosenberg, Rachel; Kelly, Susan

    2014-01-01

    Background: Studies throughout Northern Europe, the United States and Australia have found an association between childhood attention deficit hyperactivity disorder (ADHD) and family socioeconomic disadvantage. We report further evidence for the association and review potential causal pathways that might explain the link. Methods: Secondary…

  18. [Detecting shared pathways linked to rheumatoid arthritis with other autoimmune diseases in a in silico analysis].

    PubMed

    Zheng, W-Y; Zheng, W-X; Hua, L

    2016-01-01

    Pathway-based analysis approach has exploded in use during the last several years. It is successful in recognizing additional biological insight of disease and finding groupings of risk genes that represent disease developing processes. Therefore, shared pathways, with pleiotropic effects, are important for understanding similar pathogenesis and indicating the common genetic origin of certain diseases. Here, we present a pathway analysis to reveal the potential disease associations between RA and three potential RA-related autoimmune diseases: psoriasis, diabetes mellitus, type 1 (T1D) and systemic lupus erythematosus (SLE). First, a comprehensive knowledge mining of public databases is performed to discover risk genes associated with RA, T1D, SLE and psoriasis; then by enrichment test of these genes, disease-related risk pathways are detected to recognize the pathways common for RA and three other diseases. Finally, the underlying disease associations are evaluated with the association rules mining method. In total, we identify multiple RA risk pathways with significant pleiotropic effects, the most unsurprising of which are the immunology related pathways. Meanwhile for the first time we highlight the involvement of the viral myocarditis pathway related to cardiovascular disease (CVD) in autoimmune diseases such as RA, psoriasis, T1D and SLE. Further Association rule mining results validate the strong association between RA and T1D and RA and SLE. It is clear that pleiotropy is a common property of pathways associated with disease traits. We provide novel pathway associations among RA and three autoimmune diseases. These results ascertain that there are shared genetic risk profiles that predispose individuals to autoimmune diseases. PMID:27414792

  19. Exploring Links to Unorganized and Organized Physical Activity during Adolescence: The Role of Gender, Socioeconomic Status, Weight Status, and Enjoyment of Physical Education

    ERIC Educational Resources Information Center

    Bengoechea, Enrique Garcia; Sabiston, Catherine M.; Ahmed, Rashid; Farnoush, Michelle

    2010-01-01

    There is limited research on participation context in studies of physical activity correlates during adolescence. Using an ecological approach, this study explored the association of gender, socioeconomic status (SES), weight status, and physical education enjoyment with participation in organized and unorganized physical activity contexts in a…

  20. The diffusible factor synthase XanB2 is a bifunctional chorismatase that links the shikimate pathway to ubiquinone and xanthomonadins biosynthetic pathways.

    PubMed

    Zhou, Lian; Wang, Jia-Yuan; Wu, Ji'en; Wang, Jianhe; Poplawsky, Alan; Lin, Shuangjun; Zhu, Bangshang; Chang, Changqing; Zhou, Tielin; Zhang, Lian-Hui; He, Ya-Wen

    2013-01-01

    The diffusible factor synthase XanB2, originally identified in Xanthomonas campestris pv. campestris (Xcc), is highly conserved across a wide range of bacterial species, but its substrate and catalytic mechanism have not yet been investigated. Here, we show that XanB2 is a unique bifunctional chorismatase that hydrolyses chorismate, the end-product of the shikimate pathway, to produce 3-hydroxybenzoic acid (3-HBA) and 4-HBA. 3-HBA and 4-HBA are respectively associated with the yellow pigment xanthomonadin biosynthesis and antioxidant activity in Xcc. We further demonstrate that XanB2 is a structurally novel enzyme with three putative domains. It catalyses 3-HBA and 4-HBA biosynthesis via a unique mechanism with the C-terminal YjgF-like domain conferring activity for 3-HBA biosynthesis and the N-terminal FGFG motif-containing domain responsible for 4-HBA biosynthesis. Furthermore, we show that Xcc produces coenzyme Q8 (CoQ8) via a new biosynthetic pathway independent of the key chorismate-pyruvate lyase UbiC. XanB2 is the alternative source of 4-HBA for CoQ8 biosynthesis. The similar CoQ8 biosynthetic pathway, xanthomonadin biosynthetic gene cluster and XanB2 homologues are well conserved in the bacterial species within Xanthomonas, Xylella, Xylophilus, Pseudoxanthomonas, Rhodanobacter, Frateuria, Herminiimonas and Variovorax, suggesting that XanB2 may be a conserved metabolic link between the shikimate pathway, ubiquinone and xanthomonadin biosynthetic pathways in diverse bacteria. PMID:23113660

  1. Adverse outcome pathways linked to population models as a methodology for investigating effects of chemical stressors

    EPA Science Inventory

    In addressing the complexity and toxicity of chemical contaminants in Great Lakes ecosystems, we describe an approach to link chemically induced alterations in molecular and biochemical endpoints to adverse outcomes in whole organisms and populations. Analysis of population impac...

  2. A novel interaction linking the FAS-II and phthiocerol dimycocerosate (PDIM) biosynthetic pathways.

    PubMed

    Kruh, Nicole A; Borgaro, Janine G; Ruzsicska, Béla P; Xu, Hua; Tonge, Peter J

    2008-11-14

    The fatty acid biosynthesis (FAS-II) pathway in Mycobacterium tuberculosis generates long chain fatty acids that serve as the precursors to mycolic acids, essential components of the mycobacterial cell wall. Enzymes in the FAS-II pathway are thought to form one or more noncovalent multi-enzyme complexes within the cell, and a bacterial two-hybrid screen was used to search for missing components of the pathway and to furnish additional data on interactions involving these enzymes in vivo. Using the FAS-II beta-ketoacyl synthase, KasA, as bait, an extensive bacterial two-hybrid screen of a M. tuberculosis genome fragment library unexpectedly revealed a novel interaction between KasA and PpsB as well as PpsD, two polyketide modules involved in the biosynthesis of the virulence lipid phthiocerol dimycocerosate (PDIM). Sequence analysis revealed that KasA interacts with PpsB and PpsD in the region of the acyl carrier domain of each protein, raising the possibility that lipids could be transferred between the FAS-II and PDIM biosynthetic pathways. Subsequent studies utilizing purified proteins and radiolabeled lipids revealed that fatty acids loaded onto PpsB were transferred to KasA and also incorporated into long chain fatty acids synthesized using a Mycobacterium smegmatis lysate. These data suggest that in addition to producing PDIMs, the growing phthiocerol product can also be shuttled into the FAS-II pathway via KasA as an entry point for further elongation. Interactions between these biosynthetic pathways may exist as a simple means to increase mycobacterial lipid diversity, enhancing functionality and the overall complexity of the cell wall. PMID:18703500

  3. Developmental Pathways Linking Externalizing Symptoms, Internalizing Symptoms, and Academic Competence to Adolescent Substance Use

    ERIC Educational Resources Information Center

    Englund, Michelle M.; Siebenbruner, Jessica

    2012-01-01

    This study extends previous research investigating the developmental pathways predicting adolescent alcohol and marijuana use by examining the cascading effects of externalizing and internalizing symptoms and academic competence in the prediction of use and level of use of these substances in adolescence. Participants (N = 191) were drawn from a…

  4. Linking Social Change and Developmental Change: Shifting Pathways of Human Development

    ERIC Educational Resources Information Center

    Greenfield, Patricia M.

    2009-01-01

    P. M. Greenfield's new theory of social change and human development aims to show how changing sociodemographic ecologies alter cultural values and learning environments and thereby shift developmental pathways. Worldwide sociodemographic trends include movement from rural residence, informal education at home, subsistence economy, and…

  5. BRCA1: a missing link in the Fanconi anemia/BRCA pathway.

    PubMed

    D'Andrea, Alan D

    2013-04-01

    Domchek and colleagues provide a case report of a 28-year-old woman with congenital abnormalities, inherited ovarian cancer, and carboplatin hypersensitivity. Interestingly, the woman had validated germline mutations in both BRCA1 alleles. These findings further implicate BRCA1 in the Fanconi anemia/BRCA pathway and have important implications for BRCA1 genetic testing.

  6. Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway

    PubMed Central

    Fraga, Joana; Maranha, Ana; Mendes, Vitor; Pereira, Pedro José Barbosa; Empadinhas, Nuno; Macedo-Ribeiro, Sandra

    2015-01-01

    A novel four-step pathway identified recently in mycobacteria channels trehalose to glycogen synthesis and is also likely involved in the biosynthesis of two other crucial polymers: intracellular methylglucose lipopolysaccharides and exposed capsular glucan. The structures of three of the intervening enzymes - GlgB, GlgE, and TreS - were recently reported, providing the first templates for rational drug design. Here we describe the structural characterization of the fourth enzyme of the pathway, mycobacterial maltokinase (Mak), uncovering a eukaryotic-like kinase (ELK) fold, similar to methylthioribose kinases and aminoglycoside phosphotransferases. The 1.15 Å structure of Mak in complex with a non-hydrolysable ATP analog reveals subtle structural rearrangements upon nucleotide binding in the cleft between the N- and the C-terminal lobes. Remarkably, this new family of ELKs has a novel N-terminal domain topologically resembling the cystatin family of protease inhibitors. By interfacing with and restraining the mobility of the phosphate-binding region of the N-terminal lobe, Mak's unusual N-terminal domain might regulate its phosphotransfer activity and represents the most likely anchoring point for TreS, the upstream enzyme in the pathway. By completing the gallery of atomic-detail models of an essential pathway, this structure opens new avenues for the rational design of alternative anti-tubercular compounds. PMID:25619172

  7. Longitudinal direct and indirect pathways linking older sibling competence to the development of younger sibling competence.

    PubMed

    Brody, Gene H; Kim, Sooyeon; Murry, Velma McBride; Brown, Anita C

    2003-05-01

    A 4-wave longitudinal model tested direct and indirect links between older sibling (OS; M = 11.7 years) and younger sibling (YS; M = 9.2 years) competence in 152 rural African American families. Data were collected at 1-year intervals. At each wave, different teachers assessed OS competence, YS competence, and YS self-regulation. Mothers reported their own psychological functioning; mothers and YSs reported parenting practices toward the YS. OS competence was stable across time and was linked with positive changes in mothers' psychological functioning from Wave 1 to Wave 2. Mothers' Wave 2 psychological functioning was associated with involved-supportive parenting of the YS at Wave 3. OS Wave 2 competence and Wave 3 parenting were indirectly linked with Wave 4 YS competence, through Wave 3 YS self-regulation. Structural equation modeling controlled for Wave 1 YS competence; thus, the model accounted for change in YS competence across 3 years.

  8. A single transcription factor regulates evolutionarily diverse but functionally linked metabolic pathways in response to nutrient availability.

    PubMed

    Schmid, Amy K; Reiss, David J; Pan, Min; Koide, Tie; Baliga, Nitin S

    2009-01-01

    During evolution, enzyme-coding genes are acquired and/or replaced through lateral gene transfer and compiled into metabolic pathways. Gene regulatory networks evolve to fine tune biochemical fluxes through such metabolic pathways, enabling organisms to acclimate to nutrient fluctuations in a competitive environment. Here, we demonstrate that a single TrmB family transcription factor in Halobacterium salinarum NRC-1 globally coordinates functionally linked enzymes of diverse phylogeny in response to changes in carbon source availability. Specifically, during nutritional limitation, TrmB binds a cis-regulatory element to activate or repress 113 promoters of genes encoding enzymes in diverse metabolic pathways. By this mechanism, TrmB coordinates the expression of glycolysis, TCA cycle, and amino-acid biosynthesis pathways with the biosynthesis of their cognate cofactors (e.g. purine and thiamine). Notably, the TrmB-regulated metabolic network includes enzyme-coding genes that are uniquely archaeal as well as those that are conserved across all three domains of life. Simultaneous analysis of metabolic and gene regulatory network architectures suggests an ongoing process of co-evolution in which TrmB integrates the expression of metabolic enzyme-coding genes of diverse origins.

  9. A single transcription factor regulates evolutionarily diverse but functionally linked metabolic pathways in response to nutrient availability

    PubMed Central

    Schmid, Amy K; Reiss, David J; Pan, Min; Koide, Tie; Baliga, Nitin S

    2009-01-01

    During evolution, enzyme-coding genes are acquired and/or replaced through lateral gene transfer and compiled into metabolic pathways. Gene regulatory networks evolve to fine tune biochemical fluxes through such metabolic pathways, enabling organisms to acclimate to nutrient fluctuations in a competitive environment. Here, we demonstrate that a single TrmB family transcription factor in Halobacterium salinarum NRC-1 globally coordinates functionally linked enzymes of diverse phylogeny in response to changes in carbon source availability. Specifically, during nutritional limitation, TrmB binds a cis-regulatory element to activate or repress 113 promoters of genes encoding enzymes in diverse metabolic pathways. By this mechanism, TrmB coordinates the expression of glycolysis, TCA cycle, and amino-acid biosynthesis pathways with the biosynthesis of their cognate cofactors (e.g. purine and thiamine). Notably, the TrmB-regulated metabolic network includes enzyme-coding genes that are uniquely archaeal as well as those that are conserved across all three domains of life. Simultaneous analysis of metabolic and gene regulatory network architectures suggests an ongoing process of co-evolution in which TrmB integrates the expression of metabolic enzyme-coding genes of diverse origins. PMID:19536205

  10. Evidence for a common biological pathway linking three Parkinson's disease-causing genes: parkin, PINK1 and DJ-1.

    PubMed

    van der Merwe, Celia; Jalali Sefid Dashti, Zahra; Christoffels, Alan; Loos, Ben; Bardien, Soraya

    2015-05-01

    Parkinson's disease (PD) is characterised by the loss of dopaminergic neurons in the midbrain. Autosomal recessive, early-onset cases of PD are predominantly caused by mutations in the parkin, PINK1 and DJ-1 genes. Animal and cellular models have verified a direct link between parkin and PINK1, whereby PINK1 phosphorylates and activates parkin at the outer mitochondrial membrane, resulting in removal of dysfunctional mitochondria via mitophagy. Despite the overwhelming evidence for this interaction, few studies have been able to identify a link for DJ-1 with parkin or PINK1. The aim of this review is to summarise the functions of these three proteins, and to analyse the existing evidence for direct and indirect interactions between them. DJ-1 is able to rescue the phenotype of PINK1-knockout Drosophila models, but not of parkin-knockouts, suggesting that DJ-1 may act in a parallel pathway to that of the PINK1/parkin pathway. To further elucidate a commonality between these three proteins, bioinformatics analysis established that Miro (RHOT1) interacts with parkin and PINK1, and HSPA4 interacts with all three proteins. Furthermore, 30 transcription factors were found to be common amongst all three proteins, with many of them being involved in transcriptional regulation. Interestingly, expression of these proteins and their associated transcription factors are found to be significantly down-regulated in PD patients compared to healthy controls. In summary, this review provides insight into common pathways linking three PD-causing genes and highlights some key questions, the answers to which may provide critical insight into the disease process.

  11. Regulation of the protein glycosylation pathway in yeast: structural control of N-linked oligosaccharide elongation.

    PubMed Central

    Gopal, P K; Ballou, C E

    1987-01-01

    The yeast Saccharomyces cerevisiae X2180 strain with the mnn1 mnn2 mnn9 mutations, all of which affect mannoprotein glycosylation, synthesizes N-linked oligosaccharides having the following structure: (Formula: see text) whereas the mnn1 mnn2 mutant extends the alpha 1----6-linked backbone of some of the core oligosaccharides by adding 20-30 mannose units. Membrane fractions from the mnn1 mnn2 and mnn1 mnn2 mnn9 mutants are equally effective in catalyzing transfer from GDP-[3H]mannose to add mannose in both alpha 1----2 and alpha 1----6 linkages to an oligosaccharide having the following structure: (Formula: see text) but neither membrane preparation can utilize the homologous mnn1 mnn2 mnn9 oligosaccharide as an acceptor. Thus, addition of the alpha 1----2-linked mannose side chain to the terminal alpha 1----6-linked mannose in oligosaccharides of the mnn9 mutant inhibits the elongation reaction and may serve as an important structural control of mannoprotein glycosylation. The mnn9 mutation also increases the transit time for invertase secretion, meaning that this mutation could affect the processing machinery in the Golgi apparatus. PMID:3321055

  12. Predicting Ethnic Minority Children's Vocabulary from Socioeconomic Status, Maternal Language and Home Reading Input: Different Pathways for Host and Ethnic Language

    ERIC Educational Resources Information Center

    Prevoo, Mariëlle J. L.; Malda, Maike; Mesman, Judi; Emmen, Rosanneke A. G.; Yeniad, Nihal; Van Ijzendoorn, Marinus; Linting, Mariëlle

    2014-01-01

    When bilingual children enter formal reading education, host language proficiency becomes increasingly important. This study investigated the relation between socioeconomic status (SES), maternal language use, reading input, and vocabulary in a sample of 111 six-year-old children of first- and second-generation Turkish immigrant parents in the…

  13. Source Water Flow Pathways In Forested, Mountain, Headwater Streams: A Link Between Sediment Movement Patterns And Stream Water Chemistry.

    NASA Astrophysics Data System (ADS)

    Martin, S.; Conklin, M. H.; Liu, F.

    2015-12-01

    Three years of continuous and discrete sediment and water quality data, from four forested, mountain, headwater catchments in the Sierra Nevada, is used to identify water sources, determine the importance of sub-surface flow pathways, detect any changes in source waters due to seasonal variation or drought, and link flow pathways with observed patterns of in-channel sediment movement within the study watersheds. Patterns in stream chemistry and turbidity point to infiltration as the dominant flow pathway within these catchments. Data support a flow pathway conceptual model in which precipitation water infiltrates into the shallow or deeper subsurface, increasing the hydraulic head of the water table and pushing pre-event water into the stream ahead of event water. Study catchments contain perennial streams and are characterized by a Mediterranean climate with a distinct wet and dry season. Sites are located in the rain-snow transition zone with snow making up 40 to 60 percent of average annual precipitation. Barring human disturbances such as logging/grazing (compaction) or fire (hydrophobicity), catchment soils have high infiltration capacities. Springs and seeps maintain baseflow during the summer low-flow season, and shifting chemical signals within the streams indicate the increased importance of sub-surface water sources during drought years. End-member mixing analysis was conducted to identify possible water end members. Turbidity hysteresis patterns described by previous studies show in-channel sources are dominant for discharge events year round, and there is no difference in fine sediment delivery to streams with or without a soil protecting layer of snow on the land surface. The dominance of sub-surface water sources and evidence for infiltration flow fits with turbidity data, as little material is reaching the stream due to erosive overland flow. An understanding of flow pathways provides a foundation for sustainable land use management in forested

  14. Psychosis, Socioeconomic Disadvantage, and Health Service Use in South Australia: Findings from the Second Australian National Survey of Psychosis.

    PubMed

    Sweeney, Shaun; Air, Tracy; Zannettino, Lana; Galletly, Cherrie

    2015-01-01

    an important focus for mental health services. Such health policy would provide accessible treatment programs and linked pathways to illness recovery and diminish the pressure on the delivery of health services. Consequently, the development of policy and practice that seeks to redress the socioeconomic and health inequalities created by disadvantage should be an important focus for the improvement of mental health services.

  15. Conceptual disorganization weakens links in cognitive pathways: Disentangling neurocognition, social cognition, and metacognition in schizophrenia.

    PubMed

    Minor, Kyle S; Marggraf, Matthew P; Davis, Beshaun J; Luther, Lauren; Vohs, Jenifer L; Buck, Kelly D; Lysaker, Paul H

    2015-12-01

    Disentangling links between neurocognition, social cognition, and metacognition offers the potential to improve interventions for these cognitive processes. Disorganized symptoms have shown promise for explaining the limiting relationship that neurocognition holds with both social cognition and metacognition. In this study, primary aims included: 1) testing whether conceptual disorganization, a specific disorganized symptom, moderated relationships between cognitive processes, and 2) examining the level of conceptual disorganization necessary for links between cognitive processes to break down. To accomplish these aims, comprehensive assessments of conceptual disorganization, neurocognition, social cognition, and metacognition were administered to 67 people with schizophrenia-spectrum disorders. We found that conceptual disorganization significantly moderated the relationship between neurocognition and metacognition, with links between cognitive processes weakening when conceptual disorganization is present even at minimal levels of severity. There was no evidence that conceptual disorganization-or any other specific disorganized symptom-drove the limiting relationship of neurocognition on social cognition. Based on our findings, conceptual disorganization appears to be a critical piece of the puzzle when disentangling the relationship between neurocognition and metacognition. Roles of specific disorganized symptoms in the neurocognition - social cognition relationship were less clear. Findings from this study suggest that disorganized symptoms are an important treatment consideration when aiming to improve cognitive impairments.

  16. A C. elegans model of human α1-antitrypsin deficiency links components of the RNAi pathway to misfolded protein turnover

    PubMed Central

    Long, Olivia S.; Benson, Joshua A.; Kwak, Joon Hyeok; Luke, Cliff J.; Gosai, Sager J.; O'Reilly, Linda P.; Wang, Yan; Li, Jie; Vetica, Anne C.; Miedel, Mark T.; Stolz, Donna B.; Watkins, Simon C.; Züchner, Stephan; Perlmutter, David H.; Silverman, Gary A.; Pak, Stephen C.

    2014-01-01

    The accumulation of serpin oligomers and polymers within the endoplasmic reticulum (ER) causes cellular injury in patients with the classical form α1-antitrypsin deficiency (ATD). To better understand the cellular and molecular genetic aspects of this disorder, we generated transgenic C. elegans strains expressing either the wild-type (ATM) or Z mutant form (ATZ) of the human serpin fused to GFP. Animals secreted ATM, but retained polymerized ATZ within dilated ER cisternae. These latter animals also showed slow growth, smaller brood sizes and decreased longevity; phenotypes observed in ATD patients or transgenic mouse lines expressing ATZ. Similar to mammalian models, ATZ was disposed of by autophagy and ER-associated degradation pathways. Mutant strains defective in insulin signaling (daf-2) also showed a marked decrease in ATZ accumulation. Enhanced ATZ turnover was associated with the activity of two proteins central to systemic/exogenous (exo)-RNAi pathway: the dsRNA importer, SID-1 and the argonaute, RDE-1. Animals with enhanced exo-RNAi activity (rrf-3 mutant) phenocopied the insulin signaling mutants and also showed increased ATZ turnover. Taken together, these studies allude to the existence of a novel proteostasis pathway that mechanistically links misfolded protein turnover to components of the systemic RNAi machinery. PMID:24838286

  17. Human SNP Links Differential Outcomes in Inflammatory and Infectious Disease to a FOXO3-Regulated Pathway

    PubMed Central

    Lee, James C.; Espéli, Marion; Anderson, Carl A.; Linterman, Michelle A.; Pocock, Joanna M.; Williams, Naomi J.; Roberts, Rebecca; Viatte, Sebastien; Fu, Bo; Peshu, Norbert; Hien, Tran Tinh; Phu, Nguyen Hoan; Wesley, Emma; Edwards, Cathryn; Ahmad, Tariq; Mansfield, John C.; Gearry, Richard; Dunstan, Sarah; Williams, Thomas N.; Barton, Anne; Vinuesa, Carola G.; Phillips, Anne; Mowat, Craig; Drummond, Hazel; Kennedy, Nick; Lees, Charlie W.; Satsangi, Jack; Taylor, Kirstin; Prescott, Natalie J.; Mathew, Christopher G.; Simpson, Peter; Simmons, Alison; Khan, Mohammed; Newman, William G.; Hawkey, Christopher; Hart, Ailsa; Wilson, David C.; Henderson, Paul; Barrett, Jeffrey C.; Parkes, Miles; Lyons, Paul A.; Smith, Kenneth G.C.

    2013-01-01

    Summary The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses. PaperClip PMID:24035192

  18. A distinct brain pathway links viral RNA exposure to sickness behavior

    PubMed Central

    Zhu, Xinxia; Levasseur, Pete R.; Michaelis, Katherine A.; Burfeind, Kevin G.; Marks, Daniel L.

    2016-01-01

    Sickness behaviors and metabolic responses to invading pathogens are common to nearly all types of infection. These responses evolved to provide short-term benefit to the host to ward off infection, but impact on quality of life, and when prolonged lead to neurodegeneration, depression, and cachexia. Among the major infectious agents, viruses most frequently enter the brain, resulting in profound neuroinflammation. We sought to define the unique features of the inflammatory response in the brain to these infections. We demonstrate that the molecular pathway defining the central response to dsRNA is distinct from that found in the periphery. The behavioral and physical response to the dsRNA mimetic poly I:C is dependent on signaling via MyD88 when it is delivered centrally, whereas this response is mediated via the TRIF pathway when delivered peripherally. We also define the likely cellular candidates for this MyD88-dependent step. These findings suggest that symptom management is possible without ameliorating protective antiviral immune responses. PMID:27435819

  19. Characterization of the oxygen tolerance of a hydrogenase linked to a carbon monoxide oxidation pathway in Rubrivivax gelatinosus.

    PubMed

    Maness, Pin-Ching; Smolinski, Sharon; Dillon, Anne C; Heben, Michael J; Weaver, Paul F

    2002-06-01

    A hydrogenase linked to the carbon monoxide oxidation pathway in Rubrivivax gelatinosus displays tolerance to O2. When either whole-cell or membrane-free partially purified hydrogenase was stirred in full air (21% O2, 79% N2), its H2 evolution activity exhibited a half-life of 20 or 6 h, respectively, as determined by an anaerobic assay using reduced methyl viologen. When the partially purified hydrogenase was stirred in an atmosphere containing either 3.3 or 13% O2 for 15 min and evaluated by a hydrogen-deuterium (H-D) exchange assay, nearly 80 or 60% of its isotopic exchange rate was retained, respectively. When this enzyme suspension was subsequently returned to an anaerobic atmosphere, more than 90% of the H-D exchange activity was recovered, reflecting the reversibility of this hydrogenase toward O2 inactivation. Like most hydrogenases, the CO-linked hydrogenase was extremely sensitive to CO, with 50% inhibition occurring at 3.9 microM dissolved CO. Hydrogen production from the CO-linked hydrogenase was detected when ferredoxins of a prokaryotic source were the immediate electron mediator, provided they were photoreduced by spinach thylakoid membranes containing active water-splitting activity. Based on its appreciable tolerance to O2, potential applications of this hydrogenase are discussed.

  20. Characterization of the Oxygen Tolerance of a Hydrogenase Linked to a Carbon Monoxide Oxidation Pathway in Rubrivivax gelatinosus

    PubMed Central

    Maness, Pin-Ching; Smolinski, Sharon; Dillon, Anne C.; Heben, Michael J.; Weaver, Paul F.

    2002-01-01

    A hydrogenase linked to the carbon monoxide oxidation pathway in Rubrivivax gelatinosus displays tolerance to O2. When either whole-cell or membrane-free partially purified hydrogenase was stirred in full air (21% O2, 79% N2), its H2 evolution activity exhibited a half-life of 20 or 6 h, respectively, as determined by an anaerobic assay using reduced methyl viologen. When the partially purified hydrogenase was stirred in an atmosphere containing either 3.3 or 13% O2 for 15 min and evaluated by a hydrogen-deuterium (H-D) exchange assay, nearly 80 or 60% of its isotopic exchange rate was retained, respectively. When this enzyme suspension was subsequently returned to an anaerobic atmosphere, more than 90% of the H-D exchange activity was recovered, reflecting the reversibility of this hydrogenase toward O2 inactivation. Like most hydrogenases, the CO-linked hydrogenase was extremely sensitive to CO, with 50% inhibition occurring at 3.9 μM dissolved CO. Hydrogen production from the CO-linked hydrogenase was detected when ferredoxins of a prokaryotic source were the immediate electron mediator, provided they were photoreduced by spinach thylakoid membranes containing active water-splitting activity. Based on its appreciable tolerance to O2, potential applications of this hydrogenase are discussed. PMID:12039713

  1. A Genome Wide Association Study Links Glutamate Receptor Pathway to Sporadic Creutzfeldt-Jakob Disease Risk

    PubMed Central

    Sanchez-Juan, Pascual; Bishop, Matthew T.; Kovacs, Gabor G.; Calero, Miguel; Aulchenko, Yurii S.; Ladogana, Anna; Boyd, Alison; Lewis, Victoria; Ponto, Claudia; Calero, Olga; Poleggi, Anna; Carracedo, Ángel; van der Lee, Sven J.; Ströbel, Thomas; Rivadeneira, Fernando; Hofman, Albert; Haïk, Stéphane; Combarros, Onofre; Berciano, José; Uitterlinden, Andre G.; Collins, Steven J.; Budka, Herbert; Brandel, Jean-Philippe; Laplanche, Jean Louis; Pocchiari, Maurizio; Zerr, Inga; Knight, Richard S. G.; Will, Robert G.; van Duijn, Cornelia M.

    2015-01-01

    We performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a multinational consortium. From the initial GWA analysis we selected 23 SNPs for further genotyping in 1109 sCJD cases from seven different countries. Five SNPs were significantly associated with sCJD after correction for multiple testing. Subsequently these five SNPs were genotyped in 2264 controls. The pooled analysis, including 1543 sCJD cases and 4203 controls, yielded two genome wide significant results: rs6107516 (p-value=7.62x10-9) a variant tagging the prion protein gene (PRNP); and rs6951643 (p-value=1.66x10-8) tagging the Glutamate Receptor Metabotropic 8 gene (GRM8). Next we analysed the data stratifying by country of origin combining samples from the pooled analysis with genotypes from the 1000 Genomes Project and imputed genotypes from the Rotterdam Study (Total n=12967). The meta-analysis of the results showed that rs6107516 (p-value=3.00x10-8) and rs6951643 (p-value=3.91x10-5) remained as the two most significantly associated SNPs. Rs6951643 is located in an intronic region of GRM8, a gene that was additionally tagged by a cluster of 12 SNPs within our top100 ranked results. GRM8 encodes for mGluR8, a protein which belongs to the metabotropic glutamate receptor family, recently shown to be involved in the transduction of cellular signals triggered by the prion protein. Pathway enrichment analyses performed with both Ingenuity Pathway Analysis and ALIGATOR postulates glutamate receptor signalling as one of the main pathways associated with sCJD. In summary, we have detected GRM8 as a novel, non-PRNP, genome-wide significant marker associated with heightened disease risk, providing additional evidence supporting a role of glutamate receptors in sCJD pathogenesis. PMID:25918841

  2. A visual pathway links brain structures active during magnetic compass orientation in migratory birds.

    PubMed

    Heyers, Dominik; Manns, Martina; Luksch, Harald; Güntürkün, Onur; Mouritsen, Henrik

    2007-09-26

    The magnetic compass of migratory birds has been suggested to be light-dependent. Retinal cryptochrome-expressing neurons and a forebrain region, "Cluster N", show high neuronal activity when night-migratory songbirds perform magnetic compass orientation. By combining neuronal tracing with behavioral experiments leading to sensory-driven gene expression of the neuronal activity marker ZENK during magnetic compass orientation, we demonstrate a functional neuronal connection between the retinal neurons and Cluster N via the visual thalamus. Thus, the two areas of the central nervous system being most active during magnetic compass orientation are part of an ascending visual processing stream, the thalamofugal pathway. Furthermore, Cluster N seems to be a specialized part of the visual wulst. These findings strongly support the hypothesis that migratory birds use their visual system to perceive the reference compass direction of the geomagnetic field and that migratory birds "see" the reference compass direction provided by the geomagnetic field.

  3. Psychoneuroimmunology in pregnancy: immune pathways linking stress with maternal health, adverse birth outcomes, and fetal development.

    PubMed

    Christian, Lisa M

    2012-01-01

    It is well-established that psychological stress promotes immune dysregulation in nonpregnant humans and animals. Stress promotes inflammation, impairs antibody responses to vaccination, slows wound healing, and suppresses cell-mediated immune function. Importantly, the immune system changes substantially to support healthy pregnancy, with attenuation of inflammatory responses and impairment of cell-mediated immunity. This adaptation is postulated to protect the fetus from rejection by the maternal immune system. Thus, stress-induced immune dysregulation during pregnancy has unique implications for both maternal and fetal health, particularly preterm birth. However, very limited research has examined stress-immune relationships in pregnancy. The application of psychoneuroimmunology research models to the perinatal period holds great promise for elucidating biological pathways by which stress may affect adverse pregnancy outcomes, maternal health, and fetal development.

  4. Psychoneuroimmunology in Pregnancy: Immune Pathways Linking Stress with Maternal Health, Adverse Birth Outcomes, and Fetal Development

    PubMed Central

    Christian, Lisa M.

    2011-01-01

    It is well-established that psychological stress promotes immune dysregulation in nonpregnant humans and animals. Stress promotes inflammation, impairs antibody responses to vaccination, slows wound healing, and suppresses cell-mediated immune function. Importantly, the immune system changes substantially to support healthy pregnancy, with attenuation of inflammatory responses and impairment of cell-mediated immunity. This adaptation is postulated to protect the fetus from rejection by the maternal immune system. Thus, stress-induced immune dysregulation during pregnancy has unique implications for both maternal and fetal health, particularly preterm birth. However, very limited research has examined stress-immune relationships in pregnancy. The application of psychoneuroimmunology research models to the perinatal period holds great promise for elucidating biological pathways by which stress may affect adverse pregnancy outcomes, maternal health, and fetal development. PMID:21787802

  5. Membrane-to-nucleus signaling links insulin-like growth factor-1- and stem cell factor-activated pathways.

    PubMed

    Hayashi, Yujiro; Asuzu, David T; Gibbons, Simon J; Aarsvold, Kirsten H; Bardsley, Michael R; Lomberk, Gwen A; Mathison, Angela J; Kendrick, Michael L; Shen, K Robert; Taguchi, Takahiro; Gupta, Anu; Rubin, Brian P; Fletcher, Jonathan A; Farrugia, Gianrico; Urrutia, Raul A; Ordog, Tamas

    2013-01-01

    Stem cell factor (mouse: Kitl, human: KITLG) and insulin-like growth factor-1 (IGF1), acting via KIT and IGF1 receptor (IGF1R), respectively, are critical for the development and integrity of several tissues. Autocrine/paracrine KITLG-KIT and IGF1-IGF1R signaling are also activated in several cancers including gastrointestinal stromal tumors (GIST), the most common sarcoma. In murine gastric muscles, IGF1 promotes Kitl-dependent development of interstitial cells of Cajal (ICC), the non-neoplastic counterpart of GIST, suggesting cooperation between these pathways. Here, we report a novel mechanism linking IGF1-IGF1R and KITLG-KIT signaling in both normal and neoplastic cells. In murine gastric muscles, the microenvironment for ICC and GIST, human hepatic stellate cells (LX-2), a model for cancer niches, and GIST cells, IGF1 stimulated Kitl/KITLG protein and mRNA expression and promoter activity by activating several signaling pathways including AKT-mediated glycogen synthase kinase-3β inhibition (GSK3i). GSK3i alone also stimulated Kitl/KITLG expression without activating mitogenic pathways. Both IGF1 and GSK3i induced chromatin-level changes favoring transcriptional activation at the Kitl promoter including increased histone H3/H4 acetylation and H3 lysine (K) 4 methylation, reduced H3K9 and H3K27 methylation and reduced occupancy by the H3K27 methyltransferase EZH2. By pharmacological or RNA interference-mediated inhibition of chromatin modifiers we demonstrated that these changes have the predicted impact on KITLG expression. KITLG knock-down and immunoneutralization inhibited the proliferation of GIST cells expressing wild-type KIT, signifying oncogenic autocrine/paracrine KITLG-KIT signaling. We conclude that membrane-to-nucleus signaling involving GSK3i establishes a previously unrecognized link between the IGF1-IGF1R and KITLG-KIT pathways, which is active in both physiologic and oncogenic contexts and can be exploited for therapeutic purposes. PMID:24116170

  6. Inflexible ethanol intake: A putative link with the Lrrk2 pathway.

    PubMed

    da Silva E Silva, Daniel Almeida; Frozino Ribeiro, Andrea; Damasceno, Samara; Rocha, Cristiane S; Berenguer de Matos, Alexandre H; Boerngen-Lacerda, Roseli; Correia, Diego; Brunialti Godard, Ana Lúcia

    2016-10-15

    Alcoholism is a complex multifactorial disorder with a strong genetic influence. Although several studies have shown the impact of high ethanol intake on the striatal gene expression, few have addressed the relationship between the patterns of gene expression underlying the compulsive behaviour associated with the two major concerns in addiction: the excessive drug consumption and relapsing. In this study, we used a chronic three-bottle free-choice murine model to address striatal transcript regulation among animals with different ethanol intakes and preferences: Light Drinkers (preference for water throughout the experiment), Heavy Drinkers (preference for ethanol with a non-compulsive intake) and Inflexible Drinkers (preference for ethanol and simultaneous loss of control over the drug intake). Our aim was to correlate the intake patterns observed in this model with gene expression changes in the striatum, a brain region critical for the development of alcohol addiction. We found that the transcripts of the Lrrk2 gene, which encodes a multifunctional protein with kinase and GTPase activities, is upregulated only in Inflexible Drinkers suggesting, for the first time, that the Lrrk2 pathway plays a major role in the compulsive ethanol intake behaviour of addicted subjects. PMID:27411784

  7. Clostridium difficile flagella predominantly activate TLR5-linked NF-κB pathway in epithelial cells.

    PubMed

    Batah, Jameel; Denève-Larrazet, Cécile; Jolivot, Pierre-Alain; Kuehne, Sarah; Collignon, Anne; Marvaud, Jean-Christophe; Kansau, Imad

    2016-04-01

    Clostridium difficile has become the most common enteropathogen responsible for intestinal nosocomial post-antibiotic infections. This has coincided with the appearance of serious cases related to the emergence of hypervirulent strains. The toxins are the main virulence factors and elicit an inflammatory response during C. difficile infection. However, other bacterial components appear to be involved in the inflammatory process. In some pathogens, flagella play a role in pathogenesis through abnormal stimulation of the TLR5-mediated host immune response. To date, few studies have addressed this role for C. difficile flagella. In the current study, we confirm in two different epithelial cell models that C. difficile thanks to its FliC flagellin interacts with TLR5. In addition, thanks to inhibition and transcriptomic studies we demonstrate that the interaction of flagellin and TLR5 predominantly activates the NF-κB and, in a lesser degree, the MAPK pathways, via TLR5, leading to up-regulation of pro-inflammatory gene expression and synthesis of pro-inflammatory mediators. These results suggest a role for C. difficile flagella in contributing to inflammatory response in host intestinal cells. PMID:26790921

  8. Dental fluorosis linked to degassing of Ambrym volcano, Vanuatu: a novel exposure pathway.

    PubMed

    Allibone, Rachel; Cronin, Shane J; Charley, Douglas T; Neall, Vince E; Stewart, Robert B; Oppenheimer, Clive

    2012-04-01

    Ambrym in Vanuatu is a persistently degassing island volcano whose inhabitants harvest rainwater for their potable water needs. The findings from this study indicate that dental fluorosis is prevalent in the population due to fluoride contamination of rainwater by the volcanic plume. A dental survey was undertaken of 835 children aged 6-18 years using the Dean's Index of Fluorosis. Prevalence of dental fluorosis was found to be 96% in the target area of West Ambrym, 71% in North Ambrym, and 61% in Southeast Ambrym. This spatial distribution appears to reflect the prevailing winds and rainfall patterns on the island. Severe cases were predominantly in West Ambrym, the most arid part of the island, and the most commonly affected by the volcanic plume. Over 50 km downwind, on a portion of Malakula Island, the dental fluorosis prevalence was 85%, with 36% prevalence on Tongoa Island, an area rarely affected by volcanic emissions. Drinking water samples from West Ambrym contained fluoride levels from 0.7 to 9.5 ppm F (average 4.2 ppm F, n = 158) with 99% exceeding the recommended concentration of 1.0 ppm F. The pathway of fluoride-enriched rainwater impacting upon human health as identified in this study has not previously been recognised in the aetiology of fluorosis. This is an important consideration for populations in the vicinity of degassing volcanoes, particularly where rainwater comprises the primary potable water supply for humans or animals. PMID:20703513

  9. Octopamine neuromodulation regulates Gr32a-linked aggression and courtship pathways in Drosophila males.

    PubMed

    Andrews, Jonathan C; Fernández, María Paz; Yu, Qin; Leary, Greg P; Leung, Adelaine K W; Kavanaugh, Michael P; Kravitz, Edward A; Certel, Sarah J

    2014-05-01

    Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a neurons promote male aggression and form synaptic contacts with OA neurons. By restricting the monoamine neuron target population, we show that three previously identified OA-Fru(M) neurons involved in behavioral choice are among the Gr32a-OA connections. Our findings demonstrate that octopaminergic neuromodulatory neurons function as early as a second-order step in this chemosensory-driven male social behavior pathway.

  10. The GTPase Rab26 links synaptic vesicles to the autophagy pathway.

    PubMed

    Binotti, Beyenech; Pavlos, Nathan J; Riedel, Dietmar; Wenzel, Dirk; Vorbrüggen, Gerd; Schalk, Amanda M; Kühnel, Karin; Boyken, Janina; Erck, Christian; Martens, Henrik; Chua, John J E; Jahn, Reinhard

    2015-01-01

    Small GTPases of the Rab family not only regulate target recognition in membrane traffic but also control other cellular functions such as cytoskeletal transport and autophagy. Here we show that Rab26 is specifically associated with clusters of synaptic vesicles in neurites. Overexpression of active but not of GDP-preferring Rab26 enhances vesicle clustering, which is particularly conspicuous for the EGFP-tagged variant, resulting in a massive accumulation of synaptic vesicles in neuronal somata without altering the distribution of other organelles. Both endogenous and induced clusters co-localize with autophagy-related proteins such as Atg16L1, LC3B and Rab33B but not with other organelles. Furthermore, Atg16L1 appears to be a direct effector of Rab26 and binds Rab26 in its GTP-bound form, albeit only with low affinity. We propose that Rab26 selectively directs synaptic and secretory vesicles into preautophagosomal structures, suggesting the presence of a novel pathway for degradation of synaptic vesicles.

  11. Developmental pathways for social understanding: linking social cognition to social contexts

    PubMed Central

    Brink, Kimberly A.; Lane, Jonathan D.; Wellman, Henry M.

    2015-01-01

    Contemporary research, often with looking-time tasks, reveals that infants possess foundational understandings of their social worlds. However, few studies have examined how these early social cognitions relate to the child’s social interactions and behavior in early development. Does an early understanding of the social world relate to how an infant interacts with his or her parents? Do early social interactions along with social-cognitive understandings in infancy predict later preschool social competencies? In the current paper, we propose a theory in which children’s later social behaviors and their understanding of the social world depend on the integration of early social understanding and experiences in infancy. We review several of our studies, as well as other research, that directly examine the pathways between these competencies to support a hypothesized network of relations between social-cognitive development and social-interactive behaviors in the development from infancy to childhood. In total, these findings reveal differences in infant social competences that both track the developmental trajectory of infants’ understanding of people over the first years of life and provide external validation for the large body of social-cognitive findings emerging from laboratory looking-time paradigms. PMID:26074859

  12. THOC2 Mutations Implicate mRNA-Export Pathway in X-Linked Intellectual Disability

    PubMed Central

    Kumar, Raman; Corbett, Mark A.; van Bon, Bregje W.M.; Woenig, Joshua A.; Weir, Lloyd; Douglas, Evelyn; Friend, Kathryn L.; Gardner, Alison; Shaw, Marie; Jolly, Lachlan A.; Tan, Chuan; Hunter, Matthew F.; Hackett, Anna; Field, Michael; Palmer, Elizabeth E.; Leffler, Melanie; Rogers, Carolyn; Boyle, Jackie; Bienek, Melanie; Jensen, Corinna; Van Buggenhout, Griet; Van Esch, Hilde; Hoffmann, Katrin; Raynaud, Martine; Zhao, Huiying; Reed, Robin; Hu, Hao; Haas, Stefan A.; Haan, Eric; Kalscheuer, Vera M.; Gecz, Jozef

    2015-01-01

    Export of mRNA from the cell nucleus to the cytoplasm is essential for protein synthesis, a process vital to all living eukaryotic cells. mRNA export is highly conserved and ubiquitous. Mutations affecting mRNA and mRNA processing or export factors, which cause aberrant retention of mRNAs in the nucleus, are thus emerging as contributors to an important class of human genetic disorders. Here, we report that variants in THOC2, which encodes a subunit of the highly conserved TREX mRNA-export complex, cause syndromic intellectual disability (ID). Affected individuals presented with variable degrees of ID and commonly observed features included speech delay, elevated BMI, short stature, seizure disorders, gait disturbance, and tremors. X chromosome exome sequencing revealed four missense variants in THOC2 in four families, including family MRX12, first ascertained in 1971. We show that two variants lead to decreased stability of THOC2 and its TREX-complex partners in cells derived from the affected individuals. Protein structural modeling showed that the altered amino acids are located in the RNA-binding domains of two complex THOC2 structures, potentially representing two different intermediate RNA-binding states of THOC2 during RNA transport. Our results show that disturbance of the canonical molecular pathway of mRNA export is compatible with life but results in altered neuronal development with other comorbidities. PMID:26166480

  13. The Gordon Wilson Lecture: Neurohormonal Signaling Pathways That Link Cardiac Growth and Death

    PubMed Central

    Dorn, Gerald W.

    2007-01-01

    Far from being a simple muscular pump, the heart senses changes in hemodynamic forces and neurohormonal signaling, and responds by elaborating autocrine and paracrine factors that self-regulate cardiomyocyte contraction, growth, and programmed death. Interference with the afferent or efferent arms of this stress-response mechanism, as with inhibition of the β-adrenergic or renin/angiotensin systems, is a mainstay of pharmacological therapy for heart failure. However, despite striking group-mean effects showing mortality benefits of neurohormonal antagonists, inter-individual variability in the therapeutic response to these agents suggests a pharmacogenomic interaction, where common sequence variations of genes that regulate neurohormonal signaling modify the individual response to treatment. Furthermore, there is increasing evidence that, depending upon physiological milieu, conventional neurohormone receptor-ligand pairs can activate non-traditional signaling pathways, with pathological consequences. Recently, studies that integrate the findings from human gene polymorphism discovery, recombinant gene variant expression in cell and animal models, and outcome or risk analysis of polymorphisms in human disease have provided additional understanding into adaptive and maladaptive events that are the consequence of the cardiac stress-response sequence. PMID:18528498

  14. Prioritizing disease-linked variants, genes, and pathways with an interactive whole-genome analysis pipeline.

    PubMed

    Lee, In-Hee; Lee, Kyungjoon; Hsing, Michael; Choe, Yongjoon; Park, Jin-Ho; Kim, Shu Hee; Bohn, Justin M; Neu, Matthew B; Hwang, Kyu-Baek; Green, Robert C; Kohane, Isaac S; Kong, Sek Won

    2014-05-01

    Whole-genome sequencing (WGS) studies are uncovering disease-associated variants in both rare and nonrare diseases. Utilizing the next-generation sequencing for WGS requires a series of computational methods for alignment, variant detection, and annotation, and the accuracy and reproducibility of annotation results are essential for clinical implementation. However, annotating WGS with up to date genomic information is still challenging for biomedical researchers. Here, we present one of the fastest and highly scalable annotation, filtering, and analysis pipeline-gNOME-to prioritize phenotype-associated variants while minimizing false-positive findings. Intuitive graphical user interface of gNOME facilitates the selection of phenotype-associated variants, and the result summaries are provided at variant, gene, and genome levels. Moreover, the enrichment results of specific variants, genes, and gene sets between two groups or compared with population scale WGS datasets that is already integrated in the pipeline can help the interpretation. We found a small number of discordant results between annotation software tools in part due to different reporting strategies for the variants with complex impacts. Using two published whole-exome datasets of uveal melanoma and bladder cancer, we demonstrated gNOME's accuracy of variant annotation and the enrichment of loss-of-function variants in known cancer pathways. gNOME Web server and source codes are freely available to the academic community (http://gnome.tchlab.org).

  15. Inflexible ethanol intake: A putative link with the Lrrk2 pathway.

    PubMed

    da Silva E Silva, Daniel Almeida; Frozino Ribeiro, Andrea; Damasceno, Samara; Rocha, Cristiane S; Berenguer de Matos, Alexandre H; Boerngen-Lacerda, Roseli; Correia, Diego; Brunialti Godard, Ana Lúcia

    2016-10-15

    Alcoholism is a complex multifactorial disorder with a strong genetic influence. Although several studies have shown the impact of high ethanol intake on the striatal gene expression, few have addressed the relationship between the patterns of gene expression underlying the compulsive behaviour associated with the two major concerns in addiction: the excessive drug consumption and relapsing. In this study, we used a chronic three-bottle free-choice murine model to address striatal transcript regulation among animals with different ethanol intakes and preferences: Light Drinkers (preference for water throughout the experiment), Heavy Drinkers (preference for ethanol with a non-compulsive intake) and Inflexible Drinkers (preference for ethanol and simultaneous loss of control over the drug intake). Our aim was to correlate the intake patterns observed in this model with gene expression changes in the striatum, a brain region critical for the development of alcohol addiction. We found that the transcripts of the Lrrk2 gene, which encodes a multifunctional protein with kinase and GTPase activities, is upregulated only in Inflexible Drinkers suggesting, for the first time, that the Lrrk2 pathway plays a major role in the compulsive ethanol intake behaviour of addicted subjects.

  16. Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia.

    PubMed

    Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

    2016-08-11

    Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

  17. Linking Prenatal Maternal Adversity to Developmental Outcomes in Infants: The Role of Epigenetic Pathways

    PubMed Central

    Monk, Catherine; Spicer, Julie; Champagne, Frances A.

    2013-01-01

    Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with consequences for risk of psychopathology. Though the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally-induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this review, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and here we review findings illustrating prenatal-postnatal interplay and the developmental and epigenetic consequences of postnatal mother-infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress. PMID:23062303

  18. Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

    PubMed Central

    Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B.; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

    2016-01-01

    Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis. PMID:27529214

  19. Emotion regulation strategies in trauma-related disorders: pathways linking neurobiology and clinical manifestations.

    PubMed

    Del Río-Casanova, Lucía; González, Anabel; Páramo, Mario; Van Dijke, Annemiek; Brenlla, Julio

    2016-06-01

    Emotion regulation impairments with traumatic origins have mainly been studied from posttraumatic stress disorder (PTSD) models by studying cases of adult onset and single-incident trauma exposure. The effects of adverse traumatic experiences, however, go beyond the PTSD. Different authors have proposed that PTSD, borderline personality, dissociative, conversive and somatoform disorders constitute a full spectrum of trauma-related conditions. Therefore, a comprehensive review of the neurobiological findings covering this posttraumatic spectrum is needed in order to develop an all-encompassing model for trauma-related disorders with emotion regulation at its center. The present review has sought to link neurobiology findings concerning cortico-limbic function to the field of emotion regulation. In so doing, trauma-related disorders have been placed in a continuum between under- and over-regulation of affect strategies. Under-regulation of affect was predominant in borderline personality disorder, PTSD with re-experiencing symptoms and positive psychoform and somatoform dissociative symptoms. Over-regulation of affect was more prevalent in somatoform disorders and pathologies characterized by negative psychoform and somatoform symptoms. Throughout this continuum, different combinations between under- and over-regulation of affect strategies were also found. PMID:26812780

  20. Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia.

    PubMed

    Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

    2016-01-01

    Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis. PMID:27529214

  1. Identification of Links Between Cellular Pathways by Genetic Interaction Mapping (GIM).

    PubMed

    Malabat, Christophe; Saveanu, Cosmin

    2016-01-01

    The yeast systematic deletion collection offered the basis for a number of different strategies that establish functional links between genes by analyzing the phenotype of cells that combine two different deletions or mutations. A distinguishing feature of the collection is the presence of molecular barcodes at each deleted locus, which can be used to quantify the presence and abundance of cells bearing a given allele in a complex mix. As a result, a large number of mutants can be tested in batch cultures, replacing tedious manipulation of thousands of individual strains with a barcode microarray readout. Barcode-based genetic screens like Genetic Interaction Mapping (GIM) thus require little investment in terms of specific equipment, are fast to perform, and allow precise measurements of double mutant growth rates for both aggravating (synthetic sick) and alleviating (epistatic) effects. We describe here protocols for preparing the pools of haploid double mutant S. cerevisiae cells, testing their composition with barcode microarrays, and analyzing the results to extract useful functional information.

  2. Streptococcus pyogenes malate degradation pathway links pH regulation and virulence.

    PubMed

    Paluscio, Elyse; Caparon, Michael G

    2015-03-01

    The ability of Streptococcus pyogenes to infect different niches within its human host most likely relies on its ability to utilize alternative carbon sources. In examining this question, we discovered that all sequenced S. pyogenes strains possess the genes for the malic enzyme (ME) pathway, which allows malate to be used as a supplemental carbon source for growth. ME is comprised of four genes in two adjacent operons, with the regulatory two-component MaeKR required for expression of genes encoding a malate permease (maeP) and malic enzyme (maeE). Analysis of transcription indicated that expression of maeP and maeE is induced by both malate and low pH, and induction in response to both cues is dependent on the MaeK sensor kinase. Furthermore, both maePE and maeKR are repressed by glucose, which occurs via a CcpA-independent mechanism. Additionally, malate utilization requires the PTS transporter EI enzyme (PtsI), as a PtsI(-) mutant fails to express the ME genes and is unable to utilize malate. Virulence of selected ME mutants was assessed in a murine model of soft tissue infection. MaeP(-), MaeK(-), and MaeR(-) mutants were attenuated for virulence, whereas a MaeE(-) mutant showed enhanced virulence compared to that of the wild type. Taken together, these data show that ME contributes to S. pyogenes' carbon source repertory, that malate utilization is a highly regulated process, and that a single regulator controls ME expression in response to diverse signals. Furthermore, malate uptake and utilization contribute to the adaptive pH response, and ME can influence the outcome of infection.

  3. Streptococcus pyogenes Malate Degradation Pathway Links pH Regulation and Virulence

    PubMed Central

    Paluscio, Elyse

    2015-01-01

    The ability of Streptococcus pyogenes to infect different niches within its human host most likely relies on its ability to utilize alternative carbon sources. In examining this question, we discovered that all sequenced S. pyogenes strains possess the genes for the malic enzyme (ME) pathway, which allows malate to be used as a supplemental carbon source for growth. ME is comprised of four genes in two adjacent operons, with the regulatory two-component MaeKR required for expression of genes encoding a malate permease (maeP) and malic enzyme (maeE). Analysis of transcription indicated that expression of maeP and maeE is induced by both malate and low pH, and induction in response to both cues is dependent on the MaeK sensor kinase. Furthermore, both maePE and maeKR are repressed by glucose, which occurs via a CcpA-independent mechanism. Additionally, malate utilization requires the PTS transporter EI enzyme (PtsI), as a PtsI– mutant fails to express the ME genes and is unable to utilize malate. Virulence of selected ME mutants was assessed in a murine model of soft tissue infection. MaeP–, MaeK–, and MaeR– mutants were attenuated for virulence, whereas a MaeE– mutant showed enhanced virulence compared to that of the wild type. Taken together, these data show that ME contributes to S. pyogenes' carbon source repertory, that malate utilization is a highly regulated process, and that a single regulator controls ME expression in response to diverse signals. Furthermore, malate uptake and utilization contribute to the adaptive pH response, and ME can influence the outcome of infection. PMID:25583521

  4. Is ozone pre-conditioning effect linked to Nrf2/EpRE activation pathway in vivo? A preliminary result.

    PubMed

    Re, Lamberto; Martínez-Sánchez, Gregorio; Bordicchia, Marica; Malcangi, Giuseppe; Pocognoli, Antonella; Morales-Segura, Miguel Angel; Rothchild, John; Rojas, Armando

    2014-11-01

    The present preliminary study has been focused on verifying whether ozone preconditioning may be linked to Nrf2/EpRE (nuclear factor erythroid 2/electrophile-responsive element) activation pathway in vivo. Healthy volunteers received a total of three Major Auto-Hemotherapy (MAH) treatments, with treatments administered every second day. The amount of blood used for each subject was standardized to the value obtained multiplying the subject׳s body weight by 1.3 in order to ensure the same ozone concentrations for each subject. A parallel group (n=50) age and gender matched was used as reference for the experimental variables related to the oxidative stress parameters. Levels of Nrf2 and oxidative stress index were measured throughout the study. Levels of Nrf2 (P<0.01) in peripheral blood mononuclear cells (PBMC) were found to increase immediately after ozone/oxygen exposure (35µg/ml, prior to reinfusion). This effect was still detected (P<0.05) in total circulating PBMC when measured 30min following reinfusion. After a series of 3 MAH, Nrf2 returned back to the basal level. At the end of the experiment the activities of superoxide dismutase and catalase were increased (P<0.05). These data demonstrate for the first time in vivo the activation of the Nrf2 pathway by a low dose of ozone and the promotion of the feedback mechanism that induces the synthesis of proteins which collectively favors cell survival.

  5. Cell cycle-linked MeCP2 phosphorylation modulates adult neurogenesis involving the Notch signaling pathway

    PubMed Central

    Li, Hongda; Zhong, Xiaofen; Chau, Kevin Fongching; Santistevan, Nicholas J.; Guo, Weixiang; Kong, Guangyao; Li, Xuekun; Kadakia, Mitul; Masliah, Jamie; Chi, Jingyi; Jin, Peng; Zhang, Jing; Zhao, Xinyu; Chang, Qiang

    2014-01-01

    Neuronal activity regulates the phosphorylation states at multiple sites on MeCP2 in postmitotic neurons. The precise control of the phosphorylation status of MeCP2 in neurons is critical for the normal development and function of the mammalian brain. However, it is unknown whether phosphorylation at any of the previously identified sites on MeCP2 can be induced by signals other than neuronal activity in other cell types, and what functions MeCP2 phosphorylation may have in those contexts. Here we show that, in neural progenitor cells isolated from the adult mouse hippocampus, cell cycle-linked phosphorylation at serine 421 on MeCP2 is directly regulated by aurora kinase B, and modulates the balance between proliferation and neural differentiation through the Notch signaling pathway. Our findings suggest MeCP2 S421 phosphorylation may function as a general epigenetic switch accessible by different extracellular stimuli through different signaling pathways for regulating diverse biological functions in different cell types. PMID:25420914

  6. Cytochrome c, a hub linking energy, redox, stress and signaling pathways in mitochondria and other cell compartments.

    PubMed

    Welchen, Elina; Gonzalez, Daniel H

    2016-07-01

    Cytochrome c (CYTc) is a soluble redox-active heme protein that transfers electrons from complex III to complex IV in the cyanide-sensitive mitochondrial respiratory pathway. CYTc biogenesis is a complex process that requires multiple steps until the mature active protein is obtained. CYTc levels and activity are finely regulated, revealing the importance of this protein not only as electron carrier but also in many other processes. In this article, we describe the role of CYTc in mitochondrial respiration, from its canonical role as electron carrier for ATP production to its involvement in protein import and the stabilization of respiratory complexes and supercomplexes. In plants, CYTc is connected to the synthesis of the antioxidant ascorbate and the detoxification of toxic compounds. Finally, CYTc is also a multi-functional signaling molecule that influences the balance between life and death, acting in energy provision for cellular functions or triggering programmed cell death. The confluence of several metabolic routes into a single protein that links redox reactions with energy producing pathways seems logical from the point of view of cellular economy, control and organization. PMID:27080474

  7. Linking γ-aminobutyric acid A receptor to epidermal growth factor receptor pathways activation in human prostate cancer.

    PubMed

    Wu, Weijuan; Yang, Qing; Fung, Kar-Ming; Humphreys, Mitchell R; Brame, Lacy S; Cao, Amy; Fang, Yu-Ting; Shih, Pin-Tsen; Kropp, Bradley P; Lin, Hsueh-Kung

    2014-03-01

    Neuroendocrine (NE) differentiation has been attributed to the progression of castration-resistant prostate cancer (CRPC). Growth factor pathways including the epidermal growth factor receptor (EGFR) signaling have been implicated in the development of NE features and progression to a castration-resistant phenotype. However, upstream molecules that regulate the growth factor pathway remain largely unknown. Using androgen-insensitive bone metastasis PC-3 cells and androgen-sensitive lymph node metastasis LNCaP cells derived from human prostate cancer (PCa) patients, we demonstrated that γ-aminobutyric acid A receptor (GABA(A)R) ligand (GABA) and agonist (isoguvacine) stimulate cell proliferation, enhance EGF family members expression, and activate EGFR and a downstream signaling molecule, Src, in both PC-3 and LNCaP cells. Inclusion of a GABA(A)R antagonist, picrotoxin, or an EGFR tyrosine kinase inhibitor, Gefitinib (ZD1839 or Iressa), blocked isoguvacine and GABA-stimulated cell growth, trans-phospohorylation of EGFR, and tyrosyl phosphorylation of Src in both PCa cell lines. Spatial distributions of GABAAR α₁ and phosphorylated Src (Tyr416) were studied in human prostate tissues by immunohistochemistry. In contrast to extremely low or absence of GABA(A)R α₁-positive immunoreactivity in normal prostate epithelium, elevated GABA(A)R α₁ immunoreactivity was detected in prostate carcinomatous glands. Similarly, immunoreactivity of phospho-Src (Tyr416) was specifically localized and limited to the nucleoli of all invasive prostate carcinoma cells, but negative in normal tissues. Strong GABAAR α₁ immunoreactivity was spatially adjacent to the neoplastic glands where strong phospho-Src (Tyr416)-positive immunoreactivity was demonstrated, but not in adjacent to normal glands. These results suggest that the GABA signaling is linked to the EGFR pathway and may work through autocrine or paracine mechanism to promote CRPC progression.

  8. Adolescent smoking and tertiary education: opposing pathways linking socio‐economic background to alcohol consumption

    PubMed Central

    Leyland, Alastair H.; Sweeting, Helen; Benzeval, Michaela

    2016-01-01

    Abstract Background and Aims If socio‐economic disadvantage is associated with more adolescent smoking, but less participation in tertiary education, and smoking and tertiary education are both associated with heavier drinking, these may represent opposing pathways to heavy drinking. This paper examines contextual variation in the magnitude and direction of these associations. Design Comparing cohort studies. Setting United Kingdom. Participants Participants were from the 1958 National Child Development Study (NCDS58; n = 15 672), the British birth cohort study (BCS70; n = 12 735) and the West of Scotland Twenty‐07 1970s cohort (T07; n = 1515). Measurements Participants self‐reported daily smoking and weekly drinking in adolescence (age 16 years) and heavy drinking (> 14/21 units in past week) in early adulthood (ages 22–26 years). Parental occupational class (manual versus non‐manual) indicated socio‐economic background. Education beyond age 18 was coded as tertiary. Models were adjusted for parental smoking and drinking, family structure and adolescent psychiatric distress. Findings Respondents from a manual class were more likely to smoke and less likely to enter tertiary education (e.g. in NCDS58, probit coefficients were 0.201 and –0.765, respectively; P < 0.001 for both) than respondents from a non‐manual class. Adolescent smokers were more likely to drink weekly in adolescence (0.346; P < 0.001) and more likely to drink heavily in early adulthood (0.178; P < 0.001) than adolescent non‐smokers. Respondents who participated in tertiary education were more likely to drink heavily in early adulthood (0.110 for males, 0.182 for females; P < 0.001 for both) than respondents with no tertiary education. With some variation in magnitude, these associations were consistent across all three cohorts. Conclusions In Britain, young adults are more likely to drink heavily both if they smoke and participate in tertiary education (college

  9. Inhibition of the pentose phosphate pathway by dichloroacetate unravels a missing link between aerobic glycolysis and cancer cell proliferation.

    PubMed

    De Preter, Géraldine; Neveu, Marie-Aline; Danhier, Pierre; Brisson, Lucie; Payen, Valéry L; Porporato, Paolo E; Jordan, Bénédicte F; Sonveaux, Pierre; Gallez, Bernard

    2016-01-19

    Glucose fermentation through glycolysis even in the presence of oxygen (Warburg effect) is a common feature of cancer cells increasingly considered as an enticing target in clinical development. This study aimed to analyze the link between metabolism, energy stores and proliferation rates in cancer cells. We found that cell proliferation, evaluated by DNA synthesis quantification, is correlated to glycolytic efficiency in six cancer cell lines as well as in isogenic cancer cell lines. To further investigate the link between glycolysis and proliferation, a pharmacological inhibitor of the pentose phosphate pathway (PPP) was used. We demonstrated that reduction of PPP activity decreases cancer cells proliferation, with a profound effect in Warburg-phenotype cancer cells. The crucial role of the PPP in sustaining cancer cells proliferation was confirmed using siRNAs against glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the PPP. In addition, we found that dichloroacetate (DCA), a new clinically tested compound, induced a switch of glycolytic cancer cells to a more oxidative phenotype and decreased proliferation. By demonstrating that DCA decreased the activity of the PPP, we provide a new mechanism by which DCA controls cancer cells proliferation.

  10. Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy

    PubMed Central

    Creedon, Helen; Gómez-Cuadrado, Laura; Tarnauskaitė, Žygimantė; Balla, Jozef; Canel, Marta; MacLeod, Kenneth G.; Serrels, Bryan; Fraser, Craig; Unciti-Broceta, Asier; Tracey, Natasha; Le Bihan, Thierry; Klinowska, Teresa; Sims, Andrew H.; Byron, Adam; Brunton, Valerie G.

    2016-01-01

    Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapies in the treatment of HER2-positive breast cancer is a major clinical problem. To identify pathways linked to resistance, we generated HER2-positive breast cancer cell lines which are resistant to either lapatinib or AZD8931, two pan-HER family kinase inhibitors. Resistance was HER2 independent and was associated with epithelial-to-mesenchymal transition (EMT), resulting in increased proliferation and migration of the resistant cells. Using a global proteomics approach, we identified a novel set of EMT-associated proteins linked to HER2-independent resistance. We demonstrate that a subset of these EMT-associated genes is predictive of prognosis within the ERBB2 subtype of human breast cancers. Furthermore, targeting the EMT-associated kinases Src and Axl potently inhibited proliferation of the resistant cells, and inhibitors to these kinases may provide additional options for the treatment of HER2-independent resistance in tumors. PMID:26883193

  11. Inhibition of the pentose phosphate pathway by dichloroacetate unravels a missing link between aerobic glycolysis and cancer cell proliferation

    PubMed Central

    De Preter, Géraldine; Neveu, Marie-Aline; Danhier, Pierre; Brisson, Lucie; Payen, Valéry L.; Porporato, Paolo E.; Jordan, Bénédicte F.; Sonveaux, Pierre; Gallez, Bernard

    2016-01-01

    Glucose fermentation through glycolysis even in the presence of oxygen (Warburg effect) is a common feature of cancer cells increasingly considered as an enticing target in clinical development. This study aimed to analyze the link between metabolism, energy stores and proliferation rates in cancer cells. We found that cell proliferation, evaluated by DNA synthesis quantification, is correlated to glycolytic efficiency in six cancer cell lines as well as in isogenic cancer cell lines. To further investigate the link between glycolysis and proliferation, a pharmacological inhibitior of the pentose phosphate pathway (PPP) was used. We demonstrated that reduction of PPP activity decreases cancer cells proliferation, with a profound effect in Warburg-phenotype cancer cells. The crucial role of the PPP in sustaining cancer cells proliferation was confirmed using siRNAs against glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the PPP. In addition, we found that dichloroacetate (DCA), a new clinically tested compound, induced a switch of glycolytic cancer cells to a more oxidative phenotype and decreased proliferation. By demonstrating that DCA decreased the activity of the PPP, we provide a new mechanism by which DCA controls cancer cells proliferation. PMID:26543237

  12. Favorable Socioeconomic Status and Recreational Polydrug Use Are Linked With Sexual Hepatitis C Virus Transmission Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men

    PubMed Central

    Chen, Yun-Chi; Wiberg, Kjell J.; Hsieh, Yu-Hsiang; Bansal, Arun; Bolzan, Philipe; Guy, Janelle A.; Maina, Erastus N.; Cox, Andrea L.; Thio, Chloe L.

    2016-01-01

    Background. Sexual transmission of hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) is an emerging issue. Studies addressing the temporal trends and risk factors associated with incident HCV in HIV-infected MSM in the community-based primary care settings in the United States are scarce. Methods. Using a retrospective cohort study design, HCV incidence, defined as HCV antibody seroconversion, was determined in 1147 HIV-infected men receiving care at Chase Brexton Health Care clinics in Baltimore, Maryland between 2004 and 2014. Multivariate regression analyses were used to identify factors associated with incident HCV. Results. There were 42 incident HCV infections during 5242 person-years (PY) of follow up (incidence rate [IR], 8.01/1000 PY). Thirty-seven (88%) of the incident infections were in MSM, of whom 31 (84%) reported no injection-drug use (IDU). The annual IRs for MSM were 13.1–15.8/1000 PY between 2004 and 2007, decreased to 2.7–6.2/1000 PY between 2008 and 2011, and increased to 10.4/1000 PY and 13.3/1000 PY in 2013 and 2014, respectively. Injection-drug use was strongly associated with incident HCV among all MSM (IR ratio [IRR], 14.15; P = .003); however, among MSM without IDU, entering care between 2010 and 2013 (IRR, 3.32; P = .01), being employed (IRR, 3.14; P = .03), and having a history of ulcerative sexually transmitted infections (IRR, 3.70; P = .009) or of polydrug use (IRR, 5.54; P = .01) independently predicted incident HCV. Conclusions. In this cohort of HIV-infected men, a re-emerging HCV epidemic was observed from 2011 to 2014 among MSM. In addition to IDU, high-risk sexual behaviors, favorable socioeconomic status, and polydrug use fueled this increase in HCV infections. PMID:27703998

  13. Linking of Primary Care Records to Census Data to Study the Association between Socioeconomic Status and Cancer Incidence in Southern Europe: A Nation-Wide Ecological Study

    PubMed Central

    Garcia-Gil, Maria; Elorza, Josep-Maria; Banque, Marta; Comas-Cufí, Marc; Blanch, Jordi; Ramos, Rafel; Méndez-Boo, Leonardo; Hermosilla, Eduardo; Bolibar, Bonaventura; Prieto-Alhambra, Daniel

    2014-01-01

    Background Area-based measures of economic deprivation are seldom applied to large medical records databases to establish population-scale associations between deprivation and disease. Objective To study the association between deprivation and incidence of common cancer types in a Southern European region. Methods Retrospective ecological study using the SIDIAP (Information System for the Development of Research in Primary Care) database of longitudinal electronic medical records for a representative population of Catalonia (Spain) and the MEDEA index based on urban socioeconomic indicators in the Spanish census. Study outcomes were incident cervical, breast, colorectal, prostate, and lung cancer in 2009–2012. The completeness of SIDIAP cancer recording was evaluated through linkage of a geographic data subset to a hospital cancer registry. Associations between MEDEA quintiles and cancer incidence was evaluated using zero-inflated Poisson regression adjusted for sex, age, smoking, alcoholism, obesity, hypertension, and diabetes. Results SIDIAP sensitivity was 63% to 92% for the five cancers studied. There was direct association between deprivation and lung, colorectal, and cervical cancer: incidence rate ratios (IRR) 1.82 [1.64–2.01], IRR 1.60 [1.34–1.90], IRR 1.22 [1.07–1.38], respectively, comparing the most deprived to most affluent areas. In wealthy areas, prostate and breast cancers were more common: IRR 0.92 [0.80–1.00], IRR 0.91 [0.78–1.06]. Adjustment for confounders attenuated the association with lung cancer risk (fully adjusted IRR 1.16 [1.08–1.25]), reversed the direction of the association with colorectal cancer (IRR 0.90 [0.84–0.95]), and did not modify the associations with cervical (IRR 1.27 [1.11–1.45]), prostate (0.74 [0.69–0.80]), and breast (0.76 [0.71–0.81]) cancer. Conclusions Deprivation is associated differently with the occurrence of various cancer types. These results provide evidence that MEDEA is a useful, area

  14. Predicting ethnic minority children's vocabulary from socioeconomic status, maternal language and home reading input: different pathways for host and ethnic language.

    PubMed

    Prevoo, Mariëlle J L; Malda, Maike; Mesman, Judi; Emmen, Rosanneke A G; Yeniad, Nihal; Van Ijzendoorn, Marinus H; Linting, Mariëlle

    2014-09-01

    When bilingual children enter formal reading education, host language proficiency becomes increasingly important. This study investigated the relation between socioeconomic status (SES), maternal language use, reading input, and vocabulary in a sample of 111 six-year-old children of first- and second-generation Turkish immigrant parents in the Netherlands. Mothers reported on their language use with the child, frequency of reading by both parents, and availability of children's books in the ethnic and the host language. Children's Dutch and Turkish vocabulary were tested during a home visit. SES was related to maternal language use and to host language reading input. Reading input mediated the relation between SES and host language vocabulary and between maternal language use and host language vocabulary, whereas only maternal language use was related to ethnic language vocabulary. During transition to formal reading education, one should be aware that children from low-SES families receive less host language reading input.

  15. Socioeconomic Inequalities in Heart Failure.

    PubMed

    Díaz-Toro, Felipe; Verdejo, Hugo E; Castro, Pablo F

    2015-10-01

    Prevalence and incidence of chronic heart failure (CHF) has increased during the past decades. Beyond its impact on mortality rates, CHF severely impairs quality of life, particularly with the elderly and vulnerable population. Several studies have shown that CHF takes its toll mostly on the uneducated, low-income population, who exhibit impaired access to health care systems, less knowledge regarding its pathology and poorer self-care behaviors. This review summarizes the available evidence linking socioeconomic inequalities and CHF, focusing on the modifiable factors that may explain the impaired health outcomes in socioeconomically deprived populations. PMID:26462090

  16. Concanavalin A amplifies both beta-adrenergic and muscarinic cholinergic receptor-adenylate cyclase-linked pathways in cardiac myocytes.

    PubMed Central

    Rocha-Singh, K J; Hines, D K; Honbo, N Y; Karliner, J S

    1991-01-01

    Concanavalin A (Con A) is a tetrameric plant lectin that disrupts plasma membrane-cytoskeletal interactions and alters plasma membrane fluidity. We used Con A as a probe to explore beta-adrenergic and muscarinic cholinergic receptor-mediated regulation of cAMP in intact neonatal rat ventricular myocytes. Preincubation with Con A, 0.5 micrograms/ml, attenuated 1 microM (-)-norepinephrine (NE)-induced downregulation of beta-adrenergic receptors and resulted in a 50% augmentation of cAMP accumulation stimulated by 1 microM NE. Con A also augmented forskolin (1-10 microM)-stimulated cAMP accumulation by an average of 37% (P less than 0.05); however, Con A preincubation had no effect on basal or cholera toxin-stimulated cAMP content. The muscarinic cholinergic agonist carbachol (1-100 microM) decreased 1 microM NE-stimulated cAMP generation by an average of 32% (n = 7, P less than 0.05); preincubation with Con A further enhanced the inhibitory effect of carbachol by 18% (n = 7, P less than 0.05). Carbachol (1 microM) for 2 h decreased muscarinic cholinergic receptor density in whole cells by 33%; preincubation with Con A prevented this receptor downregulation. Con A pretreatment did not affect (-)-isoproterenol- or forskolin-stimulated adenylate cyclase activity in cell homogenates, suggesting that an intact cytoarchitecture is necessary for Con A to augment cAMP formation. We conclude that Con A, through its modulation of beta-adrenergic and muscarinic cholinergic receptor signaling, amplifies both stimulatory and inhibitory adenylate cyclase-linked pathways in intact neonatal ventricular myocytes. These data suggest the possibility that plasma membrane-cytoskeletal interaction is an important regulator of transmembrane signaling because interference with this interaction results in alterations in cAMP accumulation mediated by both beta-adrenergic- and muscarinic cholinergic-adenylate cyclase pathways. PMID:1653274

  17. A common pathway for O-linked protein-glycosylation and synthesis of capsule in Acinetobacter baumannii.

    PubMed

    Lees-Miller, Robert G; Iwashkiw, Jeremy A; Scott, Nichollas E; Seper, Andrea; Vinogradov, Evgeny; Schild, Stefan; Feldman, Mario F

    2013-09-01

    Multi-drug resistant strains of Acinetobacter baumannii are increasingly being isolated in hospitals worldwide. Among the virulence factors identified in this bacterium there is a general O-glycosylation system that appears to be important for biofilm formation and virulence, and the capsular polysaccharide, which is essential for resistance to complement killing. In this work, we identified a locus that is responsible for the synthesis of the O-pentasaccharide found on the glycoproteins. Besides the enzymes required for the assembly of the glycan, additional proteins typically involved in polymerization and transport of capsule were identified within or adjacently to the locus. Mutagenesis of PglC, the initiating glycosyltransferase prevented the synthesis of both glycoproteins and capsule, resulting in abnormal biofilm structures and attenuated virulence in mice. These results, together with the structural analysis of A. baumannii 17978 capsular polysaccharide via NMR, demonstrated that the pentasaccharides that decorate the glycoproteins are also the building blocks for capsule biosynthesis. Two linked subunits, but not longer glycan chains, were detected on proteins via MS. The discovery of a bifurcated pathway for O-glycosylation and capsule synthesis not only provides insight into the biology of A. baumannii but also identifies potential novel candidates for intervention against this emerging pathogen.

  18. Endocrine and Metabolic Pathways Linked to Keratoconus: Implications for the Role of Hormones in the Stromal Microenvironment

    PubMed Central

    McKay, Tina B; Hjortdal, Jesper; Sejersen, Henrik; Asara, John M; Wu, Jennifer; Karamichos, Dimitrios

    2016-01-01

    Hormones play a critical role in regulating tissue function by promoting cell survival, proliferation, and differentiation. Our study explores the influence of endocrine function in regulating metabolism and inflammatory pathways in Keratoconus (KC), which is a corneal thinning disease associated with reduced stromal deposition. KC is known to be a multifactorial disease with an elusive pathogenesis. We utilized a cross-sectional study analyzing clinical features and saliva samples from sixty-four KC patients and fourteen healthy controls. In order to determine if endocrine function varied between healthy controls and KC, we measured hormone levels in saliva and found significantly increased dehydroepiandrosterone sulfate (DHEA-S) and reduced estrone levels in KC patients compared to healthy controls. We measured significant variations in metabolites associated with pro-inflammatory processes, including myoinositol and 1-methyl-histidine, by targeted mass spectrometry. We also measured significantly increased IL-16 and stem cell factor in KC saliva samples compared to healthy controls, with higher expression of these pro-inflammatory proteins correlating with increased KC clinical grade, corneal curvature, and stromal thinning. Our results identify a novel mechanism linking KC and pro-inflammatory markers and suggest that altered hormone levels modulate metabolism, cytokine, and growth factor expression leading to increased severity of the KC condition. PMID:27157003

  19. The methyltransferase Suv39h1 links the SUMO pathway to HP1α marking at pericentric heterochromatin

    PubMed Central

    Maison, Christèle; Bailly, Delphine; Quivy, Jean-Pierre; Almouzni, Geneviève

    2016-01-01

    The trimethylation of histone H3 on lysine 9 (H3K9me3) – a mark recognized by HP1 that depends on the Suv39h lysine methyltransferases (KMTs) – has provided a basis for the reader/writer model to explain HP1 accumulation at pericentric heterochromatin in mammals. Here, we identify the Suv39h1 paralog, as a unique enhancer of HP1α sumoylation both in vitro and in vivo. The region responsible for promoting HP1α sumoylation (aa1–167) is distinct from the KMT catalytic domain and mediates binding to Ubc9. Tethering the 1–167 domain of Suv39h1 to pericentric heterochromatin, but not mutants unable to bind Ubc9, accelerates the de novo targeting of HP1α to these domains. Our results establish an unexpected feature of Suv39h1, distinct from the KMT activity, with a major role for heterochromatin formation. We discuss how linking Suv39h1 to the SUMO pathway provides conceptual implications for our general view on nuclear domain organization and physiological functions. PMID:27426629

  20. A novel inhibitor of the insulin/IGF signaling pathway protects from age-onset, neurodegeneration-linked proteotoxicity.

    PubMed

    El-Ami, Tayir; Moll, Lorna; Carvalhal Marques, Filipa; Volovik, Yuli; Reuveni, Hadas; Cohen, Ehud

    2014-02-01

    Aging manipulation is an emerging strategy aimed to postpone the manifestation of late-onset neurodegenerative disorders such as Alzheimer's (AD) and Huntington's diseases (HD) and to slow their progression once emerged. Reducing the activity of the insulin/IGF signaling cascade (IIS), a prominent aging-regulating pathway, protects worms from proteotoxicity of various aggregative proteins, including the AD-associated peptide, Aβ- and the HD-linked peptide, polyQ40. Similarly, IGF1 signaling reduction protects mice from AD-like disease. These discoveries suggest that IIS inhibitors can serve as new drugs for the treatment of neurodegenerative maladies including AD and HD. Here, we report that NT219, a novel IIS inhibitor, mediates a long-lasting, highly efficient inhibition of this signaling cascade by a dual mechanism; it reduces the autophosphorylation of the IGF1 receptor and directs the insulin receptor substrates 1 and 2 (IRS 1/2) for degradation. NT219 treatment promotes stress resistance and protects nematodes from AD- and HD-associated proteotoxicity without affecting lifespan. Our discoveries strengthen the theme that IIS inhibition has a therapeutic potential as a cure for neurodegenerative maladies and point at NT219 as a promising compound for the treatment of these disorders through a selective manipulation of aging.

  1. Different neural pathways linking personality traits and eudaimonic well-being: a resting-state functional magnetic resonance imaging study.

    PubMed

    Kong, Feng; Liu, Ling; Wang, Xu; Hu, Siyuan; Song, Yiying; Liu, Jia

    2015-06-01

    Eudaimonic well-being (EWB) is the fulfillment of human potential and a meaningful life. Previous studies have shown that personality traits, especially extraversion, neuroticism, and conscientiousness, significantly contribute to EWB. However, the neurobiological pathways linking personality and EWB are not understood. Here, we used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate this issue. Specifically, we correlated individuals' EWB scores with the regional fractional amplitude of low-frequency fluctuations (fALFF) of the brain, and then examined how personality traits predicted EWB-related spontaneous brain activity. We found that EWB was positively correlated with the fALFF in the right posterior superior temporal gyrus (pSTG) and thalamus, and negatively correlated with the strength of the thalamic-insular connectivity. More importantly, we found that personality traits influenced EWB in different ways. At the regional level, the fALFF in the pSTG and thalamus mediated the effects of neuroticism and extraversion on EWB, whereas the thalamus mediated the effect of conscientiousness on EWB. At the functional connectivity level, the thalamic-insular connectivity only mediated the effect of neuroticism on EWB. Taken together, our study provides the first evidence that EWB is associated with personality traits through different neural substrates.

  2. A diet-sensitive BAF60a-mediated pathway links hepatic bile acid metabolism to cholesterol absorption and atherosclerosis

    PubMed Central

    Meng, Zhuo-Xian; Wang, Lin; Chang, Lin; Sun, Jingxia; Bao, Jiangyin; Li, Yaqiang; Chen, Y. Eugene; Lin, Jiandie D.

    2015-01-01

    Summary Dietary nutrients interact with gene networks to orchestrate adaptive responses during metabolic stress. Here we identify Baf60a as a diet-sensitive subunit of the SWI/SNF chromatin-remodeling complexes in the mouse liver that links the consumption of fat- and cholesterol-rich diet to elevated plasma cholesterol levels. Baf60a expression was elevated in the liver following feeding with a western diet. Hepatocyte-specific inactivation of Baf60a reduced bile acid production and cholesterol absorption, and attenuated diet-induced hypercholesterolemia and atherosclerosis in mice. Baf60a stimulates expression of genes involved in bile acid synthesis, modification, and transport through a CAR/Baf60a feedforward regulatory loop. Baf60a is required for the recruitment of the SWI/SNF chromatin-remodeling complexes to facilitate an activating epigenetic switch on target genes. These studies elucidate a regulatory pathway that mediates the hyperlipidemic and atherogenic effects of western diet consumption. PMID:26586440

  3. A novel inhibitor of the insulin/IGF signaling pathway protects from age-onset, neurodegeneration-linked proteotoxicity

    PubMed Central

    El-Ami, Tayir; Moll, Lorna; Carvalhal Marques, Filipa; Volovik, Yuli; Reuveni, Hadas; Cohen, Ehud

    2014-01-01

    Aging manipulation is an emerging strategy aimed to postpone the manifestation of late-onset neurodegenerative disorders such as Alzheimer’s (AD) and Huntington’s diseases (HD) and to slow their progression once emerged. Reducing the activity of the insulin/IGF signaling cascade (IIS), a prominent aging-regulating pathway, protects worms from proteotoxicity of various aggregative proteins, including the AD-associated peptide, Aβ- and the HD-linked peptide, polyQ40. Similarly, IGF1 signaling reduction protects mice from AD-like disease. These discoveries suggest that IIS inhibitors can serve as new drugs for the treatment of neurodegenerative maladies including AD and HD. Here, we report that NT219, a novel IIS inhibitor, mediates a long-lasting, highly efficient inhibition of this signaling cascade by a dual mechanism; it reduces the autophosphorylation of the IGF1 receptor and directs the insulin receptor substrates 1 and 2 (IRS 1/2) for degradation. NT219 treatment promotes stress resistance and protects nematodes from AD- and HD-associated proteotoxicity without affecting lifespan. Our discoveries strengthen the theme that IIS inhibition has a therapeutic potential as a cure for neurodegenerative maladies and point at NT219 as a promising compound for the treatment of these disorders through a selective manipulation of aging. PMID:24261972

  4. Endocrine and Metabolic Pathways Linked to Keratoconus: Implications for the Role of Hormones in the Stromal Microenvironment.

    PubMed

    McKay, Tina B; Hjortdal, Jesper; Sejersen, Henrik; Asara, John M; Wu, Jennifer; Karamichos, Dimitrios

    2016-01-01

    Hormones play a critical role in regulating tissue function by promoting cell survival, proliferation, and differentiation. Our study explores the influence of endocrine function in regulating metabolism and inflammatory pathways in Keratoconus (KC), which is a corneal thinning disease associated with reduced stromal deposition. KC is known to be a multifactorial disease with an elusive pathogenesis. We utilized a cross-sectional study analyzing clinical features and saliva samples from sixty-four KC patients and fourteen healthy controls. In order to determine if endocrine function varied between healthy controls and KC, we measured hormone levels in saliva and found significantly increased dehydroepiandrosterone sulfate (DHEA-S) and reduced estrone levels in KC patients compared to healthy controls. We measured significant variations in metabolites associated with pro-inflammatory processes, including myoinositol and 1-methyl-histidine, by targeted mass spectrometry. We also measured significantly increased IL-16 and stem cell factor in KC saliva samples compared to healthy controls, with higher expression of these pro-inflammatory proteins correlating with increased KC clinical grade, corneal curvature, and stromal thinning. Our results identify a novel mechanism linking KC and pro-inflammatory markers and suggest that altered hormone levels modulate metabolism, cytokine, and growth factor expression leading to increased severity of the KC condition. PMID:27157003

  5. Neuropeptide Y regulates intracellular calcium through different signalling pathways linked to a Y1-receptor in rat mesenteric small arteries

    PubMed Central

    Prieto, Dolores; Buus, Carsten L; Mulvany, Michael J; Nilsson, Holger

    2000-01-01

    Simultaneous measurements of intracellular calcium concentration ([Ca2+]i) and tension were performed to clarify whether the mechanisms which cause the neuropeptide Y (NPY)-elicited contraction and potentiation of noradrenaline contractions, and the NPY inhibition of forskolin responses are linked to a single or different NPY receptor(s) in rat mesenteric small arteries.In resting arteries, NPY moderately elevated [Ca2+]i and tension. These effects were antagonized by the selective Y1 receptor antagonist, (R)-N2-(diphenacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginineamide (BIBP 3226) (apparent pKB values of 8.54±0.25 and 8.27±0.17, respectively).NPY (0.1 μM) caused a near 3 fold increase in sensitivity to noradrenaline but did not significantly modify the tension-[Ca2+]i relationship for this agonist. BIBP 3226 competitively antagonized the contractile response to NPY in arteries submaximally preconstricted with noradrenaline (pA2 7.87±0.20).In arteries activated by vasopressin, the adenylyl cyclase activator forskolin (3 μM) induced a maximum relaxation and a return of [Ca2+]i to resting levels. NPY completely inhibited these effects. The contractile responses to NPY in arteries maximally relaxed with either sodium nitroprusside (SNP) or nifedipine were not significantly higher than those evoked by the peptide at resting tension, in contrast to the contractions to NPY in forskolin-relaxed arteries. BIBP 3226 competitively antagonized the contraction to NPY in forskolin-relaxed arteries with a pA2 of 7.92±0.29.Electrical field stimulation (EFS) at 8–32 Hz caused large contractions in arteries relaxed with either forskolin or noradrenaline in the presence of phentolamine. These responses to EFS were inhibited by BIBP 3226. Similar EFS in resting, non-activated arteries did not produce any response.The present results suggest that different intracellular pathways are linked to a single NPY Y1 receptor in intact rat mesenteric small arteries, and provide

  6. Neuropeptide Y regulates intracellular calcium through different signalling pathways linked to a Y(1)-receptor in rat mesenteric small arteries.

    PubMed

    Prieto, D; Buus, C L; Mulvany, M J; Nilsson, H

    2000-04-01

    Simultaneous measurements of intracellular calcium concentration ([Ca(2+)](i)) and tension were performed to clarify whether the mechanisms which cause the neuropeptide Y (NPY)-elicited contraction and potentiation of noradrenaline contractions, and the NPY inhibition of forskolin responses are linked to a single or different NPY receptor(s) in rat mesenteric small arteries. In resting arteries, NPY moderately elevated [Ca(2+)](i) and tension. These effects were antagonized by the selective Y(1) receptor antagonist, (R)-N(2)-(diphenacetyl)-N-[(4-hydroxyphenyl)methyl]-D-argininea mide (BIBP 3226) (apparent pK(B) values of 8.54+/-0.25 and 8.27+/-0.17, respectively). NPY (0.1 microM) caused a near 3 fold increase in sensitivity to noradrenaline but did not significantly modify the tension-[Ca(2+)](i) relationship for this agonist. BIBP 3226 competitively antagonized the contractile response to NPY in arteries submaximally preconstricted with noradrenaline (pA(2) 7.87+/-0.20). In arteries activated by vasopressin, the adenylyl cyclase activator forskolin (3 microM) induced a maximum relaxation and a return of [Ca(2+)](i) to resting levels. NPY completely inhibited these effects. The contractile responses to NPY in arteries maximally relaxed with either sodium nitroprusside (SNP) or nifedipine were not significantly higher than those evoked by the peptide at resting tension, in contrast to the contractions to NPY in forskolin-relaxed arteries. BIBP 3226 competitively antagonized the contraction to NPY in forskolin-relaxed arteries with a pA(2) of 7.92+/-0.29. Electrical field stimulation (EFS) at 8-32 Hz caused large contractions in arteries relaxed with either forskolin or noradrenaline in the presence of phentolamine. These responses to EFS were inhibited by BIBP 3226. Similar EFS in resting, non-activated arteries did not produce any response. The present results suggest that different intracellular pathways are linked to a single NPY Y(1) receptor in intact rat

  7. Taurine protected kidney from oxidative injury through mitochondrial-linked pathway in a rat model of nephrolithiasis.

    PubMed

    Li, Cheng Yang; Deng, Yao Liang; Sun, Bing Hua

    2009-08-01

    Hyperoxaluria and crystal deposition induce oxidative stress (OS) and renal epithelial cells injury, both mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are considered as the main sources of reactive oxygen species (ROS). Taurine is known to have antioxidant activity and shows renoprotective effect. We investigate the effect of taurine treatment on renal protection, and the putative source of ROS, in a rat model of calcium oxalate nephrolithiasis. Rats were administered with 2.5% (V/V) ethylene glycol + 2.5% (W/V) ammonium chloride (4 ml/day), with restriction on intake of drinking water (20 ml/day) for 4 weeks. Simultaneous treatment with taurine (2% W/W, mixed with the chow) was performed. At the end of the study, indexes of OS and renal injury were assessed. Renal tubular ultrastructure changes were analyzed under transmission electron microscopy. Crystal deposition in kidney was scored under light microscopy. Angiotensin II in kidney homogenates was determined by radioimmunoassay. Expression of NADPH oxidase subunits p47phox and Nox-4 mRNAs in kidney was evaluated by real time-polymerase chain reaction. The data showed that oxidative injury of the kidney occurred in nephrolithiasis-induced rats. Hyperplasia of mitochondria developed in renal tubular epithelium. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mitochondria decreased and the mitochondrial membrane showed oxidative injury. Taurine treatment alleviated the oxidative injury of the kidney, improved SOD and GSH-Px activities, as well as the mitochondrial membrane injury, with lesser crystal depositions in the kidney. We could not detect statistical changes in the renal angiotensin II level, and the renal p47phox and Nox-4 mRNAs expression in those rats. The results suggest that mitochondria but not NADPH oxidase may account for the OS and taurine protected kidney from oxidative injury through mitochondrial-linked pathway in this rat

  8. Melanoregulin, product of the dsu locus, links the BLOC-pathway and OA1 in organelle biogenesis.

    PubMed

    Rachel, Rivka A; Nagashima, Kunio; O'Sullivan, T Norene; Frost, Laura S; Stefano, Frank P; Marigo, Valeria; Boesze-Battaglia, Kathleen

    2012-01-01

    Humans with Hermansky-Pudlak Syndrome (HPS) or ocular albinism (OA1) display abnormal aspects of organelle biogenesis. The multigenic disorder HPS displays broad defects in biogenesis of lysosome-related organelles including melanosomes, platelet dense granules, and lysosomes. A phenotype of ocular pigmentation in OA1 is a smaller number of macromelanosomes, in contrast to HPS, where in many cases the melanosomes are smaller than normal. In these studies we define the role of the Mreg(dsu) gene, which suppresses the coat color dilution of Myo5a, melanophilin, and Rab27a mutant mice in maintaining melanosome size and distribution. We show that the product of the Mreg(dsu) locus, melanoregulin (MREG), interacts both with members of the HPS BLOC-2 complex and with Oa1 in regulating melanosome size. Loss of MREG function facilitates increase in the size of micromelanosomes in the choroid of the HPS BLOC-2 mutants ruby, ruby2, and cocoa, while a transgenic mouse overexpressing melanoregulin corrects the size of retinal pigment epithelium (RPE) macromelanosomes in Oa1(ko/ko) mice. Collectively, these results suggest that MREG levels regulate pigment incorporation into melanosomes. Immunohistochemical analysis localizes melanoregulin not to melanosomes, but to small vesicles in the cytoplasm of the RPE, consistent with a role for this protein in regulating membrane interactions during melanosome biogenesis. These results provide the first link between the BLOC pathway and Oa1 in melanosome biogenesis, thus supporting the hypothesis that intracellular G-protein coupled receptors may be involved in the biogenesis of other organelles. Furthermore these studies provide the foundation for therapeutic approaches to correct the pigment defects in the RPE of HPS and OA1.

  9. Melanoregulin, product of the dsu locus, links the BLOC-pathway and OA1 in organelle biogenesis.

    PubMed

    Rachel, Rivka A; Nagashima, Kunio; O'Sullivan, T Norene; Frost, Laura S; Stefano, Frank P; Marigo, Valeria; Boesze-Battaglia, Kathleen

    2012-01-01

    Humans with Hermansky-Pudlak Syndrome (HPS) or ocular albinism (OA1) display abnormal aspects of organelle biogenesis. The multigenic disorder HPS displays broad defects in biogenesis of lysosome-related organelles including melanosomes, platelet dense granules, and lysosomes. A phenotype of ocular pigmentation in OA1 is a smaller number of macromelanosomes, in contrast to HPS, where in many cases the melanosomes are smaller than normal. In these studies we define the role of the Mreg(dsu) gene, which suppresses the coat color dilution of Myo5a, melanophilin, and Rab27a mutant mice in maintaining melanosome size and distribution. We show that the product of the Mreg(dsu) locus, melanoregulin (MREG), interacts both with members of the HPS BLOC-2 complex and with Oa1 in regulating melanosome size. Loss of MREG function facilitates increase in the size of micromelanosomes in the choroid of the HPS BLOC-2 mutants ruby, ruby2, and cocoa, while a transgenic mouse overexpressing melanoregulin corrects the size of retinal pigment epithelium (RPE) macromelanosomes in Oa1(ko/ko) mice. Collectively, these results suggest that MREG levels regulate pigment incorporation into melanosomes. Immunohistochemical analysis localizes melanoregulin not to melanosomes, but to small vesicles in the cytoplasm of the RPE, consistent with a role for this protein in regulating membrane interactions during melanosome biogenesis. These results provide the first link between the BLOC pathway and Oa1 in melanosome biogenesis, thus supporting the hypothesis that intracellular G-protein coupled receptors may be involved in the biogenesis of other organelles. Furthermore these studies provide the foundation for therapeutic approaches to correct the pigment defects in the RPE of HPS and OA1. PMID:22984402

  10. Molecular pathway activation features linked with transition from normal skin to primary and metastatic melanomas in human.

    PubMed

    Shepelin, Denis; Korzinkin, Mikhail; Vanyushina, Anna; Aliper, Alexander; Borisov, Nicolas; Vasilov, Raif; Zhukov, Nikolay; Sokov, Dmitry; Prassolov, Vladimir; Gaifullin, Nurshat; Zhavoronkov, Alex; Bhullar, Bhupinder; Buzdin, Anton

    2016-01-01

    Melanoma is the most aggressive and dangerous type of skin cancer, but its molecular mechanisms remain largely unclear. For transcriptomic data of 478 primary and metastatic melanoma, nevi and normal skin samples, we performed high-throughput analysis of intracellular molecular networks including 592 signaling and metabolic pathways. We showed that at the molecular pathway level, the formation of nevi largely resembles transition from normal skin to primary melanoma. Using a combination of bioinformatic machine learning algorithms, we identified 44 characteristic signaling and metabolic pathways connected with the formation of nevi, development of primary melanoma, and its metastases. We created a model describing formation and progression of melanoma at the level of molecular pathway activation. We discovered six novel associations between activation of metabolic molecular pathways and progression of melanoma: for allopregnanolone biosynthesis, L-carnitine biosynthesis, zymosterol biosynthesis (inhibited in melanoma), fructose 2, 6-bisphosphate synthesis and dephosphorylation, resolvin D biosynthesis (activated in melanoma), D-myo-inositol hexakisphosphate biosynthesis (activated in primary, inhibited in metastatic melanoma). Finally, we discovered fourteen tightly coordinated functional clusters of molecular pathways. This study helps to decode molecular mechanisms underlying the development of melanoma. PMID:26624979

  11. Molecular pathway activation features linked with transition from normal skin to primary and metastatic melanomas in human

    PubMed Central

    Shepelin, Denis; Korzinkin, Mikhail; Vanyushina, Anna; Aliper, Alexander; Borisov, Nicolas; Vasilov, Raif; Zhukov, Nikolay; Sokov, Dmitry; Prassolov, Vladimir; Gaifullin, Nurshat; Zhavoronkov, Alex; Bhullar, Bhupinder; Buzdin, Anton

    2016-01-01

    Melanoma is the most aggressive and dangerous type of skin cancer, but its molecular mechanisms remain largely unclear. For transcriptomic data of 478 primary and metastatic melanoma, nevi and normal skin samples, we performed high-throughput analysis of intracellular molecular networks including 592 signaling and metabolic pathways. We showed that at the molecular pathway level, the formation of nevi largely resembles transition from normal skin to primary melanoma. Using a combination of bioinformatic machine learning algorithms, we identified 44 characteristic signaling and metabolic pathways connected with the formation of nevi, development of primary melanoma, and its metastases. We created a model describing formation and progression of melanoma at the level of molecular pathway activation. We discovered six novel associations between activation of metabolic molecular pathways and progression of melanoma: for allopregnanolone biosynthesis, L-carnitine biosynthesis, zymosterol biosynthesis (inhibited in melanoma), fructose 2, 6-bisphosphate synthesis and dephosphorylation, resolvin D biosynthesis (activated in melanoma), D-myo-inositol hexakisphosphate biosynthesis (activated in primary, inhibited in metastatic melanoma). Finally, we discovered fourteen tightly coordinated functional clusters of molecular pathways. This study helps to decode molecular mechanisms underlying the development of melanoma. PMID:26624979

  12. Molecular pathway activation features linked with transition from normal skin to primary and metastatic melanomas in human.

    PubMed

    Shepelin, Denis; Korzinkin, Mikhail; Vanyushina, Anna; Aliper, Alexander; Borisov, Nicolas; Vasilov, Raif; Zhukov, Nikolay; Sokov, Dmitry; Prassolov, Vladimir; Gaifullin, Nurshat; Zhavoronkov, Alex; Bhullar, Bhupinder; Buzdin, Anton

    2016-01-01

    Melanoma is the most aggressive and dangerous type of skin cancer, but its molecular mechanisms remain largely unclear. For transcriptomic data of 478 primary and metastatic melanoma, nevi and normal skin samples, we performed high-throughput analysis of intracellular molecular networks including 592 signaling and metabolic pathways. We showed that at the molecular pathway level, the formation of nevi largely resembles transition from normal skin to primary melanoma. Using a combination of bioinformatic machine learning algorithms, we identified 44 characteristic signaling and metabolic pathways connected with the formation of nevi, development of primary melanoma, and its metastases. We created a model describing formation and progression of melanoma at the level of molecular pathway activation. We discovered six novel associations between activation of metabolic molecular pathways and progression of melanoma: for allopregnanolone biosynthesis, L-carnitine biosynthesis, zymosterol biosynthesis (inhibited in melanoma), fructose 2, 6-bisphosphate synthesis and dephosphorylation, resolvin D biosynthesis (activated in melanoma), D-myo-inositol hexakisphosphate biosynthesis (activated in primary, inhibited in metastatic melanoma). Finally, we discovered fourteen tightly coordinated functional clusters of molecular pathways. This study helps to decode molecular mechanisms underlying the development of melanoma.

  13. Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework

    PubMed Central

    Teeguarden, Justin. G.; Tan, Yu-Mei; Edwards, Stephen W.; Leonard, Jeremy A.; Anderson, Kim A.; Corley, Richard A.; Harding, Anna K; Kile, Molly L.; Simonich, Staci M; Stone, David; Tanguay, Robert L.; Waters, Katrina M.; Harper, Stacey L.; Williams, David E.

    2016-01-01

    Synopsis Driven by major scientific advances in analytical methods, biomonitoring, computational tools, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the “systems approaches” used in the biological sciences is a necessary step in this evolution. Here we propose the Aggregate Exposure Pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the Adverse Outcome Pathway (AOP) concept in the toxicological sciences. Aggregate exposure pathways offer an intuitive framework to organize exposure data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathways and adverse outcome pathways, completing the source to outcome continuum for more efficient integration of exposure assessment and hazard identification. Together, the two pathways form and inform a decision-making framework with the flexibility for risk-based, hazard-based, or exposure-based decision making. PMID:26759916

  14. L-xylo-3-hexulose reductase is the missing link in the oxidoreductive pathway for D-galactose catabolism in filamentous fungi.

    PubMed

    Mojzita, Dominik; Herold, Silvia; Metz, Benjamin; Seiboth, Bernhard; Richard, Peter

    2012-07-27

    In addition to the well established Leloir pathway for the catabolism of d-galactose in fungi, the oxidoreductive pathway has been recently identified. In this oxidoreductive pathway, D-galactose is converted via a series of NADPH-dependent reductions and NAD(+)-dependent oxidations into D-fructose. The pathway intermediates include galactitol, L-xylo-3-hexulose, and d-sorbitol. This study identified the missing link in the pathway, the L-xylo-3-hexulose reductase that catalyzes the conversion of L-xylo-3-hexulose to D-sorbitol. In Trichoderma reesei (Hypocrea jecorina) and Aspergillus niger, we identified the genes lxr4 and xhrA, respectively, that encode the l-xylo-3-hexulose reductases. The deletion of these genes resulted in no growth on galactitol and in reduced growth on D-galactose. The LXR4 was heterologously expressed, and the purified protein showed high specificity for L-xylo-3-hexulose with a K(m) = 2.0 ± 0.5 mm and a V(max) = 5.5 ± 1.0 units/mg. We also confirmed that the product of the LXR4 reaction is D-sorbitol.

  15. Psychosis, Socioeconomic Disadvantage, and Health Service Use in South Australia: Findings from the Second Australian National Survey of Psychosis

    PubMed Central

    Sweeney, Shaun; Air, Tracy; Zannettino, Lana; Galletly, Cherrie

    2015-01-01

    an important focus for mental health services. Such health policy would provide accessible treatment programs and linked pathways to illness recovery and diminish the pressure on the delivery of health services. Consequently, the development of policy and practice that seeks to redress the socioeconomic and health inequalities created by disadvantage should be an important focus for the improvement of mental health services. PMID:26636059

  16. Psychological pathways linking social support to health outcomes: a visit with the "ghosts" of research past, present, and future.

    PubMed

    Uchino, Bert N; Bowen, Kimberly; Carlisle, McKenzie; Birmingham, Wendy

    2012-04-01

    Contemporary models postulate the importance of psychological mechanisms linking perceived and received social support to physical health outcomes. In this review, we examine studies that directly tested the potential psychological mechanisms responsible for links between social support and health-relevant physiological processes (1980s-2010). Inconsistent with existing theoretical models, no evidence was found that psychological mechanisms such as depression, perceived stress, and other affective processes are directly responsible for links between support and health. We discuss the importance of considering statistical/design issues, emerging conceptual perspectives, and limitations of our existing models for future research aimed at elucidating the psychological mechanisms responsible for links between social support and physical health outcomes.

  17. Completing the link between exposure science and toxicology for improved environmental health decision making: The aggregate exposure pathway framework

    DOE PAGES

    Teeguarden, Justin G.; Tan, Yu -Mei; Edwards, Stephen W.; Leonard, Jeremy A.; Anderson, Kim A.; Corley, Richard A.; Kile, Molly L.; Simonich, Staci M.; Stone, David; Tanguay, Robert L.; et al

    2016-01-13

    Here, driven by major scientific advances in analytical methods, biomonitoring, computation, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the “systems approaches” used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) concept in the toxicological sciences.more » Aggregate exposure pathways offer an intuitive framework to organize exposure data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathways and adverse outcome pathways, completing the source to outcome continuum for more meaningful integration of exposure assessment and hazard identification. Together, the two frameworks form and inform a decision-making framework with the flexibility for risk-based, hazard-based, or exposure-based decision making.« less

  18. Causal Link between the Cortico-Rubral Pathway and Functional Recovery through Forced Impaired Limb Use in Rats with Stroke

    PubMed Central

    Ishida, Akimasa; Isa, Kaoru; Umeda, Tatsuya; Kobayashi, Kazuto; Kobayashi, Kenta; Hida, Hideki

    2016-01-01

    Intensive rehabilitation is believed to induce use-dependent plasticity in the injured nervous system; however, its causal relationship to functional recovery is unclear. Here, we performed systematic analysis of the effects of forced use of an impaired forelimb on the recovery of rats after lesioning the internal capsule with intracerebral hemorrhage (ICH). Forced limb use (FLU) group rats exhibited better recovery of skilled forelimb functions and their cortical motor area with forelimb representation was restored and enlarged on the ipsilesional side. In addition, abundant axonal sprouting from the reemerged forelimb area was found in the ipsilateral red nucleus after FLU. To test the causal relationship between the plasticity in the cortico-rubral pathway and recovery, loss-of-function experiments were conducted using a double-viral vector technique, which induces selective blockade of the target pathway. Blockade of the cortico-rubral tract resulted in deficits of the recovered forelimb function in FLU group rats. These findings suggest that the cortico-rubral pathway is a substrate for recovery induced by intensive rehabilitation after ICH. SIGNIFICANCE STATEMENT The research aimed at determining the causal linkage between reorganization of the motor pathway induced by intensive rehabilitative training and recovery after stroke. We clarified the expansion of the forelimb representation area of the ipsilesional motor cortex by forced impaired forelimb use (FLU) after lesioning the internal capsule with intracerebral hemorrhaging (ICH) in rats. Anterograde tracing showed robust axonal sprouting from the forelimb area to the red nucleus in response to FLU. Selective blockade of the cortico-rubral pathway by the novel double-viral vector technique clearly revealed that the increased cortico-rubral axonal projections had causal linkage to the recovery of reaching movements induced by FLU. Our data demonstrate that the cortico-rubral pathway is responsible for the

  19. Socioeconomic Disparities and Influenza Hospitalizations, Tennessee, USA.

    PubMed

    Sloan, Chantel; Chandrasekhar, Rameela; Mitchel, Edward; Schaffner, William; Lindegren, Mary Lou

    2015-09-01

    We examined population-based surveillance data from the Tennessee Emerging Infections Program to determine whether neighborhood socioeconomic status was associated with influenza hospitalization rates. Hospitalization data collected during October 2007-April 2014 were geocoded (N = 1,743) and linked to neighborhood socioeconomic data. We calculated age-standardized annual incidence rates, relative index of inequality, and concentration curves for socioeconomic variables. Influenza hospitalizations increased with increased percentages of persons who lived in poverty, had female-headed households, lived in crowded households, and lived in population-dense areas. Influenza hospitalizations decreased with increased percentages of persons who were college educated, were employed, and had health insurance. Higher incidence of influenza hospitalization was also associated with lower neighborhood socioeconomic status when data were stratified by race. PMID:26292106

  20. Linking the physical and the socio-economic compartments of an integrated water and land use management model on a river basin scale using an object-oriented water supply model

    NASA Astrophysics Data System (ADS)

    Barthel, Roland; Nickel, Darla; Meleg, Alejandro; Trifkovic, Aleksandar; Braun, Juergen

    Within the framework of the research project ‘GLOWA-Danube’, a model of the water supply sector has been developed. GLOWA-Danube investigates long-term changes in the water cycle of the Upper Danube river basin in light of global change. For this purpose, the decision support system DANUBIA, comprising 15 fully coupled models, has been developed. Within DANUBIA the water supply model (‘WaterSupply’) forms the link between various physical models determining water quality and availability and several socio-economic models determining water consumption and demand. Having a central focus on public drinking water supply, its purpose is to correctly simulate the present day system of water extraction and distribution and the related costs, but also to allow meaningful response to possible future changes of boundary conditions, first and foremost changes in water demand or water availability and quality. Response mechanisms are also envisioned for changes in political and economic boundary conditions, and advances in technology. The model will be used locate critical regions which could experience water stress in the future, but does not aim to find the appropriate solutions or to predict the optimal organisation of water supply in the Danube Basin under such changing conditions. In the object-oriented model structure, both water supply companies (WSC) and communities are represented by main classes. Both classes have a limited view and knowledge of their environment. A community knows where and how much water is consumed and from which WSC it is served. A WSC possesses information regarding extraction sites and water rights, raw water quality and potential collaborating WSC. The WSC can perform actions that are different from ‘business as usual’. These deviations from their usual behaviour can be interpreted by decision makers but should not be regarded as a replacement for the decision-making process itself. The model is conceptualised using object

  1. Modeling Socioeconomic Status Effects on Language Development

    ERIC Educational Resources Information Center

    Thomas, Michael S. C.; Forrester, Neil A.; Ronald, Angelica

    2013-01-01

    Socioeconomic status (SES) is an important environmental predictor of language and cognitive development, but the causal pathways by which it operates are unclear. We used a computational model of development to explore the adequacy of manipulations of environmental information to simulate SES effects in English past-tense acquisition, in a data…

  2. Neural Correlates of Socioeconomic Status in the Developing Human Brain

    ERIC Educational Resources Information Center

    Noble, Kimberly G.; Houston, Suzanne M.; Kan, Eric; Sowell, Elizabeth R.

    2012-01-01

    Socioeconomic disparities in childhood are associated with remarkable differences in cognitive and socio-emotional development during a time when dramatic changes are occurring in the brain. Yet, the neurobiological pathways through which socioeconomic status (SES) shapes development remain poorly understood. Behavioral evidence suggests that…

  3. A Functional 4-Hydroxysalicylate/Hydroxyquinol Degradative Pathway Gene Cluster Is Linked to the Initial Dibenzo-p-Dioxin Pathway Genes in Sphingomonas sp. Strain RW1

    PubMed Central

    Armengaud, Jean; Timmis, Kenneth N.; Wittich, Rolf-Michael

    1999-01-01

    The bacterium Sphingomonas sp. strain RW1 is able to use dibenzo-p-dioxin, dibenzofuran, and several hydroxylated derivatives as sole sources of carbon and energy. We have determined and analyzed the nucleic acid sequence of a 9,997-bp HindIII fragment downstream of cistrons dxnA1A2, which encode the dioxygenase component of the initial dioxygenase system of the corresponding catabolic pathways. This fragment contains 10 colinear open reading frames (ORFs), apparently organized in one compact operon. The enzymatic activities of some proteins encoded by these genes were analyzed in the strain RW1 and, after hyperexpression, in Escherichia coli. The first three ORFs of the locus, designated dxnC, ORF2, and fdx3, specify a protein with a low homology to bacterial siderophore receptors, a polypeptide representing no significant homology to known proteins, and a putative ferredoxin, respectively. dxnD encodes a 69-kDa phenol monooxygenase-like protein with activity for the turnover of 4-hydroxysalicylate, and dxnE codes for a 37-kDa protein whose sequence and activity are similar to those of known maleylacetate reductases. The following gene, dxnF, encodes a 33-kDa intradiol dioxygenase which efficiently cleaves hydroxyquinol, yielding maleylacetate, the ketoform of 3-hydroxy-cis,cis-muconate. The heteromeric protein encoded by dxnGH is a 3-oxoadipate succinyl coenzyme A (succinyl-CoA) transferase, whereas dxnI specifies a protein exhibiting marked homology to acetyl-CoA acetyltransferases (thiolases). The last ORF of the sequenced fragment codes for a putative transposase. DxnD, DxnF, DxnE, DxnGH, and DxnI (the activities of most of them have also been detected in strain RW1) thus form a complete 4-hydroxysalicylate/hydroxyquinol degradative pathway. A route for the mineralization of the growth substrates 3-hydroxydibenzofuran and 2-hydroxydibenzo-p-dioxin in Sphingomonas sp. strain RW1 thus suggests itself. PMID:10348858

  4. Depression and the Link with Cardiovascular Disease

    PubMed Central

    Dhar, Arup K.; Barton, David A.

    2016-01-01

    This review provides an outline of the association between major depressive disorder (MDD) and coronary heart disease (CHD). Much is known about the two individual clinical conditions; however, it is not until recently, biological mechanisms have been uncovered that link both MDD and CHD. The activation of stress pathways have been implicated as a neurochemical mechanism that links MDD and CHD. Depression is known to be associated with poorer outcomes of CHD. Psychological factors, such as major depression and stress, are now known as risk factors for developing CHD, which is as important and is independent of classic risk factors, such as hypertension, diabetes mellitus, and cigarette smoking. Both conditions have great socioeconomic importance given that depression and CHD are likely to be two of the three leading causes of global burden of disease. Better understanding of the common causal pathways will help us delineate more appropriate treatments. PMID:27047396

  5. Depression and the Link with Cardiovascular Disease.

    PubMed

    Dhar, Arup K; Barton, David A

    2016-01-01

    This review provides an outline of the association between major depressive disorder (MDD) and coronary heart disease (CHD). Much is known about the two individual clinical conditions; however, it is not until recently, biological mechanisms have been uncovered that link both MDD and CHD. The activation of stress pathways have been implicated as a neurochemical mechanism that links MDD and CHD. Depression is known to be associated with poorer outcomes of CHD. Psychological factors, such as major depression and stress, are now known as risk factors for developing CHD, which is as important and is independent of classic risk factors, such as hypertension, diabetes mellitus, and cigarette smoking. Both conditions have great socioeconomic importance given that depression and CHD are likely to be two of the three leading causes of global burden of disease. Better understanding of the common causal pathways will help us delineate more appropriate treatments. PMID:27047396

  6. Genetic link between Cabeza, a Drosophila homologue of Fused in Sarcoma (FUS), and the EGFR signaling pathway

    SciTech Connect

    Shimamura, Mai; Kyotani, Akane; Azuma, Yumiko; Yoshida, Hideki; Binh Nguyen, Thanh; Mizuta, Ikuko; Yoshida, Tomokatsu; Mizuno, Toshiki; Nakagawa, Masanori; Tokuda, Takahiko; Yamaguchi, Masamitsu

    2014-08-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive muscular weakness. Fused in Sarcoma (FUS) that has been identified in familial ALS is an RNA binding protein that is normally localized in the nucleus. However, its function in vivo is not fully understood. Drosophila has Cabeza (Caz) as a FUS homologue and specific knockdown of Caz in the eye imaginal disc and pupal retina using a GMR-GAL4 driver was here found to induce an abnormal morphology of the adult compound eyes, a rough eye phenotype. This was partially suppressed by expression of the apoptosis inhibitor P35. Knockdown of Caz exerted no apparent effect on differentiation of photoreceptor cells. However, immunostaining with an antibody to Cut that marks cone cells revealed fusion of these and ommatidia of pupal retinae. These results indicate that Caz knockdown induces apoptosis and also inhibits differentiation of cone cells, resulting in abnormal eye morphology in adults. Mutation in EGFR pathway-related genes, such as rhomboid-1, rhomboid-3 and mirror suppressed the rough eye phenotype induced by Caz knockdown. Moreover, the rhomboid-1 mutation rescued the fusion of cone cells and ommatidia observed in Caz knockdown flies. The results suggest that Caz negatively regulates the EGFR signaling pathway required for determination of cone cell fate in Drosophila. - Highlights: • Knockdown of Cabeza induced rough eye phenotype. • Knockdown of Cabeza induced fusion of cone cells in pupal retinae. • Knockdown of Cabeza induced apoptosis in pupal retinae. • Mutation in EGFR pathway-related genes suppressed the rough eye phenotype. • Cabeza may negatively regulate the EGFR pathway.

  7. Malic Enzyme and Malolactic Enzyme Pathways Are Functionally Linked but Independently Regulated in Lactobacillus casei BL23

    PubMed Central

    Landete, José María; Ferrer, Sergi; Monedero, Vicente

    2013-01-01

    Lactobacillus casei is the only lactic acid bacterium in which two pathways for l-malate degradation have been described: the malolactic enzyme (MLE) and the malic enzyme (ME) pathways. Whereas the ME pathway enables L. casei to grow on l-malate, MLE does not support growth. The mle gene cluster consists of three genes encoding MLE (mleS), the putative l-malate transporter MleT, and the putative regulator MleR. The mae gene cluster consists of four genes encoding ME (maeE), the putative transporter MaeP, and the two-component system MaeKR. Since both pathways compete for the same substrate, we sought to determine whether they are coordinately regulated and their role in l-malate utilization as a carbon source. Transcriptional analyses revealed that the mle and mae genes are independently regulated and showed that MleR acts as an activator and requires internalization of l-malate to induce the expression of mle genes. Notwithstanding, both l-malate transporters were required for maximal l-malate uptake, although only an mleT mutation caused a growth defect on l-malate, indicating its crucial role in l-malate metabolism. However, inactivation of MLE resulted in higher growth rates and higher final optical densities on l-malate. The limited growth on l-malate of the wild-type strain was correlated to a rapid degradation of the available l-malate to l-lactate, which cannot be further metabolized. Taken together, our results indicate that L. casei l-malate metabolism is not optimized for utilization of l-malate as a carbon source but for deacidification of the medium by conversion of l-malate into l-lactate via MLE. PMID:23835171

  8. Malic enzyme and malolactic enzyme pathways are functionally linked but independently regulated in Lactobacillus casei BL23.

    PubMed

    Landete, José María; Ferrer, Sergi; Monedero, Vicente; Zúñiga, Manuel

    2013-09-01

    Lactobacillus casei is the only lactic acid bacterium in which two pathways for l-malate degradation have been described: the malolactic enzyme (MLE) and the malic enzyme (ME) pathways. Whereas the ME pathway enables L. casei to grow on l-malate, MLE does not support growth. The mle gene cluster consists of three genes encoding MLE (mleS), the putative l-malate transporter MleT, and the putative regulator MleR. The mae gene cluster consists of four genes encoding ME (maeE), the putative transporter MaeP, and the two-component system MaeKR. Since both pathways compete for the same substrate, we sought to determine whether they are coordinately regulated and their role in l-malate utilization as a carbon source. Transcriptional analyses revealed that the mle and mae genes are independently regulated and showed that MleR acts as an activator and requires internalization of l-malate to induce the expression of mle genes. Notwithstanding, both l-malate transporters were required for maximal l-malate uptake, although only an mleT mutation caused a growth defect on l-malate, indicating its crucial role in l-malate metabolism. However, inactivation of MLE resulted in higher growth rates and higher final optical densities on l-malate. The limited growth on l-malate of the wild-type strain was correlated to a rapid degradation of the available l-malate to l-lactate, which cannot be further metabolized. Taken together, our results indicate that L. casei l-malate metabolism is not optimized for utilization of l-malate as a carbon source but for deacidification of the medium by conversion of l-malate into l-lactate via MLE. PMID:23835171

  9. Corona cell RNA sequencing from individual oocytes revealed transcripts and pathways linked to euploid oocyte competence and live birth.

    PubMed

    Parks, Jason C; Patton, Alyssa L; McCallie, Blair R; Griffin, Darren K; Schoolcraft, William B; Katz-Jaffe, Mandy G

    2016-05-01

    Corona cells surround the oocyte and maintain a close relationship through transzonal processes and gap junctions, and may be used to assess oocyte competence. In this study, the corona cell transcriptome of individual cumulus oocyte complexes (COCs) was investigated. Isolated corona cells were collected from COCs that developed into euploid blastocysts and were transferred in a subsequent frozen embryo transfer. Ten corona cell samples underwent RNA-sequencing to generate unique gene expression profiles. Live birth was compared with negative implantation after the transfer of a euploid blastocyst using bioinformatics and statistical analysis. Individual corona cell samples produced a mean of 21.2 million sequence reads, and 307 differentially expressed transcrpits (P < 0.05; fold change ≥ 2). Enriched pathway analysis showed Wnt signalling, mitogen-activated protein kinases signalling, focal adhesion and tricarboxylic acid cycle to be affected by implantation outcome. The Wnt/beta-catenin signalling pathway, including genes APC, AXIN and GSK3B, were independently validated by real-time quantitative reverse transcription. Individual, corona cell transcriptome was successfully generated using RNA-sequencing. Key genes and signalling pathways were identified in association with implantation outcome after the transfer of a euploid blastocyst in a frozen embryo transfer. These data could provide novel biomarkers for the non-invasive assessment of embryo viability.

  10. Synthetic promoters consisting of defined cis-acting elements link multiple signaling pathways to probenazole-inducible system * #

    PubMed Central

    Zhu, Zheng; Gao, Jiong; Yang, Jin-xiao; Wang, Xiao-yan; Ren, Guo-dong; Ding, Yu-long; Kuai, Ben-ke

    2015-01-01

    Probenazole (3-allyloxy-1,2-benzisothiazole-1,1-dioxide, PBZ), the active component of Oryzemate, could induce systemic acquired resistance (SAR) in plants through the induction of salicylic acid (SA) biosynthesis. As a widely used chemical inducer, PBZ is a good prospect for establishing a new chemical-inducible system. We first designed artificially synthetic promoters with tandem copies of a single type of cis-element (SARE, JERE, GCC, GST1, HSRE, and W-box) that could mediate the expression of the β-glucuronidase (GUS) reporter gene in plants upon PBZ treatment. Then we combined different types of elements in order to improve inducibility in the PBZ-inducible system. On the other hand, we were surprised to find that the cis-elements, which are responsive to jasmonic acid (JA) and ethylene, also responded to PBZ, implying that SA, JA, and ethylene pathways also would play important roles in PBZ’s action. Further analysis demonstrated that PBZ also induced early events of innate immunity via a signaling pathway in which Ca2+ influx and mitogen-activated protein kinase (MAPK) activity were involved. We constructed synthesized artificial promoters to establish a PBZ chemical-inducible system, and preliminarily explored SA, JA, ethylene, calcium, and MAPK signaling pathways via PBZ-inducible system, which could provide an insight for in-depth study. PMID:25845359

  11. Disturbance of proteasomal and autophagic protein degradation pathways by amyotrophic lateral sclerosis-linked mutations in ubiquilin 2.

    PubMed

    Osaka, Mayuko; Ito, Daisuke; Suzuki, Norihiro

    2016-04-01

    Ubiquilin (UBQLN), a member of the ubiquitin-like (UBL)-ubiquitin-associated (UBA) family, is a dual regulator of both the proteasomal and autophagic branches of the cellular protein degradation system. Mutations in the UBQLN2 gene encoding ubiquilin 2 cause X-linked amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD), and UBQLN2-positive inclusions have been identified in ALS patients with UBQLN2 mutations as well as in cases of both familial and sporadic ALS without UBQLN2 mutations. Compelling evidence links UBQLN2 to disturbance of the protein quality control network in neurons, but the pathomechanisms remain obscure. This study aimed to clarify how ALS-linked mutations in UBQLN2 affect the protein degradation system. Overexpression of a UBQLN2 with ALS-associated mutations resulted in the accumulation of polyubiquitinated proteins in neuronal cells, including the ALS-associated protein TDP-43. This effect was dependent on the UBA domain but not on inclusion formation. Immunocytochemistry and protein fractionation analysis of IVm-UBQLN2 cellular distribution indicated that it sequesters ubiquitinated substrates from both the proteasomal and autophagic branches of the protein degradation system, resulting in accumulation of polyubiquitinated substrates. These findings provide a molecular basis for the development of ALS/FTD-associated proteinopathy and establish novel therapeutic targets for ALS.

  12. Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin-proteasome pathway and mitochondria to neurodegeneration.

    PubMed

    Figueiredo-Pereira, Maria E; Rockwell, Patricia; Schmidt-Glenewinkel, Thomas; Serrano, Peter

    2014-01-01

    The immune response of the CNS is a defense mechanism activated upon injury to initiate repair mechanisms while chronic over-activation of the CNS immune system (termed neuroinflammation) may exacerbate injury. The latter is implicated in a variety of neurological and neurodegenerative disorders such as Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, HIV dementia, and prion diseases. Cyclooxygenases (COX-1 and COX-2), which are key enzymes in the conversion of arachidonic acid into bioactive prostanoids, play a central role in the inflammatory cascade. J2 prostaglandins are endogenous toxic products of cyclooxygenases, and because their levels are significantly increased upon brain injury, they are actively involved in neuronal dysfunction induced by pro-inflammatory stimuli. In this review, we highlight the mechanisms by which J2 prostaglandins (1) exert their actions, (2) potentially contribute to the transition from acute to chronic inflammation and to the spreading of neuropathology, (3) disturb the ubiquitin-proteasome pathway and mitochondrial function, and (4) contribute to neurodegenerative disorders such as Alzheimer and Parkinson diseases, and amyotrophic lateral sclerosis, as well as stroke, traumatic brain injury (TBI), and demyelination in Krabbe disease. We conclude by discussing the therapeutic potential of targeting the J2 prostaglandin pathway to prevent/delay neurodegeneration associated with neuroinflammation. In this context, we suggest a shift from the traditional view that cyclooxygenases are the most appropriate targets to treat neuroinflammation, to the notion that J2 prostaglandin pathways and other neurotoxic prostaglandins downstream from cyclooxygenases, would offer significant benefits as more effective therapeutic targets to treat chronic neurodegenerative diseases, while minimizing adverse side effects. PMID:25628533

  13. Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin-proteasome pathway and mitochondria to neurodegeneration

    PubMed Central

    Figueiredo-Pereira, Maria E.; Rockwell, Patricia; Schmidt-Glenewinkel, Thomas; Serrano, Peter

    2015-01-01

    The immune response of the CNS is a defense mechanism activated upon injury to initiate repair mechanisms while chronic over-activation of the CNS immune system (termed neuroinflammation) may exacerbate injury. The latter is implicated in a variety of neurological and neurodegenerative disorders such as Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, HIV dementia, and prion diseases. Cyclooxygenases (COX-1 and COX-2), which are key enzymes in the conversion of arachidonic acid into bioactive prostanoids, play a central role in the inflammatory cascade. J2 prostaglandins are endogenous toxic products of cyclooxygenases, and because their levels are significantly increased upon brain injury, they are actively involved in neuronal dysfunction induced by pro-inflammatory stimuli. In this review, we highlight the mechanisms by which J2 prostaglandins (1) exert their actions, (2) potentially contribute to the transition from acute to chronic inflammation and to the spreading of neuropathology, (3) disturb the ubiquitin-proteasome pathway and mitochondrial function, and (4) contribute to neurodegenerative disorders such as Alzheimer and Parkinson diseases, and amyotrophic lateral sclerosis, as well as stroke, traumatic brain injury (TBI), and demyelination in Krabbe disease. We conclude by discussing the therapeutic potential of targeting the J2 prostaglandin pathway to prevent/delay neurodegeneration associated with neuroinflammation. In this context, we suggest a shift from the traditional view that cyclooxygenases are the most appropriate targets to treat neuroinflammation, to the notion that J2 prostaglandin pathways and other neurotoxic prostaglandins downstream from cyclooxygenases, would offer significant benefits as more effective therapeutic targets to treat chronic neurodegenerative diseases, while minimizing adverse side effects. PMID:25628533

  14. Linking genome content to biofuel production yields: a meta-analysis of major catabolic pathways among select H2 and ethanol-producing bacteria

    PubMed Central

    2012-01-01

    to have little impact on H2 production in organisms that do not encode ethanol producing pathways, they do influence reduced end-product yields in those that do. Conclusions Here we show that composition of genes encoding pathways involved in pyruvate catabolism and end-product synthesis pathways can be used to approximate potential end-product distribution patterns. We have identified a number of genetic biomarkers for streamlining ethanol and H2 producing capabilities. By linking genome content, reaction thermodynamics, and end-product yields, we offer potential targets for optimization of either ethanol or H2 yields through metabolic engineering. PMID:23249097

  15. Identification of a gene involved in the biosynthesis pathway of the terminal sugar of the archaellin N-linked tetrasaccharide in Methanococcus maripaludis.

    PubMed

    Ding, Yan; Jones, Gareth M; Brimacombe, Cedric; Uchida, Kaoru; Aizawa, Shin-Ichi; Logan, Susan M; Kelly, John F; Jarrell, Ken F

    2016-01-01

    In Methanococcus maripaludis, the three archaellins which comprise the archaellum are modified at multiple sites with an N-linked tetrasaccharide with the structure of Sug-4-β-ManNAc3NAmA6Thr-4-β-GlcNAc3NAcA-3-β-GalNAc, where Sug is a unique sugar (5S)-2-acetamido-2,4-dideoxy-5-O-methyl-L-erythro-hexos-5-ulo-1,5-pyranose, so far found exclusively in this species. In this study, a six-gene cluster mmp1089-1094, neighboring one of the genomic regions already known to contain genes involved with the archaellin N-glycosylation pathway, was examined for its potential involvement in the archaellin N-glycosylation or sugar biosynthesis pathway. The co-transcription of these six genes was demonstrated by RT-PCR. Mutants carrying an in-frame deletion in mmp1090, mmp1091 or mmp1092 were successfully generated. The Δmmp1090 deletion mutant was archaellated when examined by electron microscopy and mass spectrometry analysis of purified archaella showed that the archaellins were modified with a truncated N-glycan in which the terminal sugar residue and the threonine linked to the third sugar residue were missing. Both gene annotation and bioinformatic analyses indicate that MMP1090 is a UDP-glucose 4-epimerase, suggesting that the unique terminal sugar of the archaellin N-glycan might be synthesised from UDP-glucose or UDP-N-acetylglucosamine with an essential early step in synthesis catalysed by MMP1090. In contrast, no detectable phenotype related to archaellin glycosylation was observed in mutants deleted for either mmp1091 or mmp1092 while attempts to delete mmp1089, mmp1093 and mmp1094 were unsuccessful. Based on its demonstrated involvement in the archaellin N-glycosylation pathway, we designated mmp1090 as aglW. PMID:26590834

  16. MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked

    PubMed Central

    Dobó, József; Szakács, Dávid; Oroszlán, Gábor; Kortvely, Elod; Kiss, Bence; Boros, Eszter; Szász, Róbert; Závodszky, Péter; Gál, Péter; Pál, Gábor

    2016-01-01

    MASP-3 was discovered 15 years ago as the third mannan-binding lectin (MBL)-associated serine protease of the complement lectin pathway. Lacking any verified substrate its role remained ambiguous. MASP-3 was shown to compete with a key lectin pathway enzyme MASP-2 for MBL binding, and was therefore considered to be a negative complement regulator. Later, knock-out mice experiments suggested that MASP-1 and/or MASP-3 play important roles in complement pro-factor D (pro-FD) maturation. However, studies on a MASP-1/MASP-3-deficient human patient produced contradicting results. In normal resting blood unperturbed by ongoing coagulation or complement activation, factor D is present predominantly in its active form, suggesting that resting blood contains at least one pro-FD activating proteinase that is not a direct initiator of coagulation or complement activation. We have recently showed that all three MASPs can activate pro-FD in vitro. In resting blood, however, using our previously evolved MASP-1 and MASP-2 inhibitors we proved that neither MASP-1 nor MASP-2 activates pro-FD. Other plasma proteinases, particularly MASP-3, remained candidates for that function. For this study we evolved a specific MASP-3 inhibitor and unambiguously proved that activated MASP-3 is the exclusive pro-FD activator in resting blood, which demonstrates a fundamental link between the lectin and alternative pathways. PMID:27535802

  17. Linking family economic pressure and supportive parenting to adolescent health behaviors: two developmental pathways leading to health promoting and health risk behaviors.

    PubMed

    Kwon, Josephine A; Wickrama, K A S

    2014-07-01

    Adolescent health behaviors, especially health risk behaviors, have previously been linked to distal (i.e., family economic pressure) and proximal (i.e., parental support) contributors. However, few studies have examined both types of contributors along with considering health promoting and health risk behaviors separately. The present study investigated the influences of family economic hardship, supportive parenting as conceptualized by self-determination theory, and individual psychosocial and behavioral characteristics (i.e., mastery and delinquency, respectively) on adolescents' health promoting and health risk behaviors. We used structural equation modeling to analyze longitudinal data from a sample of Caucasian adolescent children and their mothers and fathers (N = 407, 54 % female) to examine direct and indirect effects, as well as gender symmetry and asymmetry. Findings suggest that family economic pressure contributed to adolescent mastery and delinquency through supportive parenting. Further, supportive parenting indirectly affected adolescent health risk behaviors only through delinquency, whereas supportive parenting indirectly influenced health promoting behaviors only through mastery, suggesting different developmental pathways for adolescent health risk and health promoting behaviors. Testing for gender symmetry of the full model showed that maternal and paternal parenting contributed to females' health risk behaviors directly, while maternal and paternal parenting contributed to males' health risk behaviors through delinquency. Gender symmetry was largely unsupported. The study highlights key direct and indirect pathways to adolescent health risk and health promoting behaviors within a family stress model and self-determination theory framework, and also highlights important gender differences in these developmental pathways.

  18. Evidence that the Entamoeba histolytica Mitochondrial Carrier Family Links Mitosomal and Cytosolic Pathways through Exchange of 3'-Phosphoadenosine 5'-Phosphosulfate and ATP.

    PubMed

    Mi-ichi, Fumika; Nozawa, Akira; Yoshida, Hiroki; Tozawa, Yuzuru; Nozaki, Tomoyoshi

    2015-11-01

    Entamoeba histolytica, a microaerophilic protozoan parasite, possesses mitosomes. Mitosomes are mitochondrion-related organelles that have largely lost typical mitochondrial functions, such as those involved in the tricarboxylic acid cycle and oxidative phosphorylation. The biological roles of Entamoeba mitosomes have been a long-standing enigma. We previously demonstrated that sulfate activation, which is not generally compartmentalized to mitochondria, is a major function of E. histolytica mitosomes. Sulfate activation cooperates with cytosolic enzymes, i.e., sulfotransferases (SULTs), for the synthesis of sulfolipids, one of which is cholesteryl sulfate. Notably, cholesteryl sulfate plays an important role in encystation, an essential process in the Entamoeba life cycle. These findings identified a biological role for Entamoeba mitosomes; however, they simultaneously raised a new issue concerning how the reactions of the pathway, separated by the mitosomal membranes, cooperate. Here, we demonstrated that the E. histolytica mitochondrial carrier family (EhMCF) has the capacity to exchange 3'-phosphoadenosine 5'-phosphosulfate (PAPS) with ATP. We also confirmed the cytosolic localization of all the E. histolytica SULTs, suggesting that in Entamoeba, PAPS, which is produced through mitosomal sulfate activation, is translocated to the cytosol and becomes a substrate for SULTs. In contrast, ATP, which is produced through cytosolic pathways, is translocated into the mitosomes and is a necessary substrate for sulfate activation. Taking our findings collectively, we suggest that EhMCF functions as a PAPS/ATP antiporter and plays a crucial role in linking the mitosomal sulfate activation pathway to cytosolic SULTs for the production of sulfolipids.

  19. MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked.

    PubMed

    Dobó, József; Szakács, Dávid; Oroszlán, Gábor; Kortvely, Elod; Kiss, Bence; Boros, Eszter; Szász, Róbert; Závodszky, Péter; Gál, Péter; Pál, Gábor

    2016-01-01

    MASP-3 was discovered 15 years ago as the third mannan-binding lectin (MBL)-associated serine protease of the complement lectin pathway. Lacking any verified substrate its role remained ambiguous. MASP-3 was shown to compete with a key lectin pathway enzyme MASP-2 for MBL binding, and was therefore considered to be a negative complement regulator. Later, knock-out mice experiments suggested that MASP-1 and/or MASP-3 play important roles in complement pro-factor D (pro-FD) maturation. However, studies on a MASP-1/MASP-3-deficient human patient produced contradicting results. In normal resting blood unperturbed by ongoing coagulation or complement activation, factor D is present predominantly in its active form, suggesting that resting blood contains at least one pro-FD activating proteinase that is not a direct initiator of coagulation or complement activation. We have recently showed that all three MASPs can activate pro-FD in vitro. In resting blood, however, using our previously evolved MASP-1 and MASP-2 inhibitors we proved that neither MASP-1 nor MASP-2 activates pro-FD. Other plasma proteinases, particularly MASP-3, remained candidates for that function. For this study we evolved a specific MASP-3 inhibitor and unambiguously proved that activated MASP-3 is the exclusive pro-FD activator in resting blood, which demonstrates a fundamental link between the lectin and alternative pathways.

  20. MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked.

    PubMed

    Dobó, József; Szakács, Dávid; Oroszlán, Gábor; Kortvely, Elod; Kiss, Bence; Boros, Eszter; Szász, Róbert; Závodszky, Péter; Gál, Péter; Pál, Gábor

    2016-01-01

    MASP-3 was discovered 15 years ago as the third mannan-binding lectin (MBL)-associated serine protease of the complement lectin pathway. Lacking any verified substrate its role remained ambiguous. MASP-3 was shown to compete with a key lectin pathway enzyme MASP-2 for MBL binding, and was therefore considered to be a negative complement regulator. Later, knock-out mice experiments suggested that MASP-1 and/or MASP-3 play important roles in complement pro-factor D (pro-FD) maturation. However, studies on a MASP-1/MASP-3-deficient human patient produced contradicting results. In normal resting blood unperturbed by ongoing coagulation or complement activation, factor D is present predominantly in its active form, suggesting that resting blood contains at least one pro-FD activating proteinase that is not a direct initiator of coagulation or complement activation. We have recently showed that all three MASPs can activate pro-FD in vitro. In resting blood, however, using our previously evolved MASP-1 and MASP-2 inhibitors we proved that neither MASP-1 nor MASP-2 activates pro-FD. Other plasma proteinases, particularly MASP-3, remained candidates for that function. For this study we evolved a specific MASP-3 inhibitor and unambiguously proved that activated MASP-3 is the exclusive pro-FD activator in resting blood, which demonstrates a fundamental link between the lectin and alternative pathways. PMID:27535802

  1. The Nuclear Factor κB pathway: A link to the immune system in the radiation response.

    PubMed

    Hellweg, Christine E

    2015-11-28

    Exposure to ionizing radiation modulates immune responses in a complex dose-dependent pattern, with possible anti-inflammatory effects in the low dose range, expression of pro-inflammatory cytokines at moderate doses and immunosuppression after exposure to higher doses due to precursor cell death together with concomitant exacerbated innate immune responses. A central regulator in the immune system is the transcription factor Nuclear Factor κB (NF-κB). NF-κB is involved in the regulation of cellular survival, immune responses and inflammation, resulting in eminent importance in cancerogenesis. After exposure to ionizing radiation, NF-κB activation is initially triggered by ATM which is activated by DNA double strand breaks. Together with the NF-κB essential modulator (NEMO), it serves as a nucleoplasmic shuttle. The pathway converges with the classical NF-κB pathway at IκB kinase (IKK) complex activation. Resulting cytokine expression can activate NF-κB in a positive feed forward loop. Danger signals released from dying cells can activate NF-κB via Toll-like receptors (TLRs). The resulting immune activation can be beneficial or detrimental. In the low dose range, pro- and anticancerogenic effects are possible. In the radiotherapy-relevant dose range, tolerogenic immune responses should be avoided, and an anti-tumor immune response might be supported by TLR agonists activating NF-κB.

  2. Novel regulatory action of ribosomal inactivation on epithelial Nod2-linked proinflammatory signals in two convergent ATF3-associated pathways.

    PubMed

    Park, Seong-Hwan; Do, Kee Hun; Choi, Hye Jin; Kim, Juil; Kim, Ki-Hyung; Park, Jiyeon; Oh, Chang Gyu; Moon, Yuseok

    2013-11-15

    In response to excessive nucleotide-binding oligomerization domain-containing protein 2 (Nod2) stimulation caused by mucosal bacterial components, gut epithelia need to activate regulatory machinery to maintain epithelial homeostasis. Activating transcription factor 3 (ATF3) is a representative regulator in the negative feedback loop that modulates TLR-associated inflammatory responses. In the current study, the regulatory effects of ribosomal stress-induced ATF3 on Nod2-stimulated proinflammatory signals were assessed. Ribosomal inactivation caused persistent ATF3 expression that in turn suppressed proinflammatory chemokine production facilitated by Nod2. Decreased chemokine production was due to attenuation of Nod2-activated NF-κB and early growth response protein 1 (EGR-1) signals by ATF3. However, the underlying molecular mechanisms involve two convergent regulatory pathways. Although ATF3 induced by ribosomal inactivation regulated Nod2-induced EGR-1 expression epigenetically through the recruitment of histone deacetylase 1, NF-κB regulation was associated with posttranscriptional regulation by ATF3 rather than epigenetic modification. ATF3 induced by ribosomal inactivation led to the destabilization of p65 mRNA caused by nuclear entrapment of transcript-stabilizing human Ag R protein via direct interaction with ATF3. These findings demonstrate that ribosomal stress-induced ATF3 is a critical regulator in the convergent pathways between EGR-1 and NF-κB, which contributes to the suppression of Nod2-activated proinflammatory gene expression.

  3. A novel functional link between MAP kinase cascades and the Ras/cAMP pathway that regulates survival.

    PubMed

    Cherkasova, Vera A; McCully, Ryan; Wang, Yunmei; Hinnebusch, Alan; Elion, Elaine A

    2003-07-15

    In mammalian cells, Ras regulates multiple effectors, including activators of mitogen-activated protein kinase (MAPK) cascades, phosphatidylinositol-3-kinase, and guanine nucleotide exchange factors (GEFs) for RalGTPases. In S. cerevisiae, Ras regulates the Kss1 MAPK cascade that promotes filamentous growth and cell integrity, but its major function is to activate adenylyl cyclase and control proliferation and survival ([; see Figure S1 in the Supplemental Data available with this article online). Previous work hints that the mating Fus3/Kss1 MAPK cascade cross-regulates the Ras/cAMP pathway during growth and mating, but direct evidence is lacking. Here, we report that Kss1 and Fus3 act upstream of the Ras/cAMP pathway to regulate survival. Loss of Fus3 increases cAMP and causes poor long-term survival and resistance to stress. These effects are dependent on Kss1 and Ras2. Activation of Kss1 by a hyperactive Ste11 MAPKKK also increases cAMP, but mating receptor/scaffold activation has little effect and may therefore insulate the MAPKs from cross-regulation. Catalytically inactive Fus3 represses cAMP by blocking accumulation of active Kss1 and by another function also shared by Kss1. The conserved RasGEF Cdc25 is a likely control point, because Kss1 and Fus3 complexes associate with and phosphorylate Cdc25. Cross-regulation of Cdc25 may be a general way that MAPKs control Ras signaling networks. PMID:12867033

  4. Non-targeted metabolomic approach reveals urinary metabolites linked to steroid biosynthesis pathway after ingestion of citrus juice.

    PubMed

    Medina, S; Ferreres, F; García-Viguera, C; Horcajada, M N; Orduna, J; Savirón, M; Zurek, G; Martínez-Sanz, J M; Gil, J I; Gil-Izquierdo, A

    2013-01-15

    Citrus juice intake has been highlighted because of its health-promoting effects. LC-MS based metabolomics approaches are applied to obtain a better knowledge on changes in the concentration of metabolites due to its dietary intake and allow a better understanding of involved metabolic pathways. Eight volunteers daily consumed 400 mL of juice for four consecutive days and urine samples were collected before intake and 24h after each citrus juice intake. Urine samples were analysed by nanoHPLC-q-TOF, followed by principal component analysis (PCA) and Student's t-test (p<0.05). PCA showed a separation between two groups (before and after citrus juice consumption). This approach allowed the identification of four endocrine compounds (tetrahydroaldosterone-3-glucuronide, cortolone-3-glucuronide, testosterone-glucuronide and 17-hydroxyprogesterone), which belonged to the steroid biosynthesis pathway as significant metabolites upregulated by citrus juice intake. Additionally, these results confirmed the importance of using the non-targeted metabolomics technique to identify new endogenous metabolites, up- or down-regulated as a consequence of food intake.

  5. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

    SciTech Connect

    Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole; Testa, Mauro; Tang, Shikui; Gheorghiu, Liliana; Biggs, Peter; Paganetti, Harald; Efstathiou, Jason A.; Lu, Hsiao-Ming; Held, Kathryn D.; Willers, Henning

    2015-04-01

    Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and {sup 137}Cs γ-rays were used. To estimate the RBE of protons relative to {sup 60}Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.

  6. Hedonic tone and activation level in the mood-creativity link: toward a dual pathway to creativity model.

    PubMed

    De Dreu, Carsten K W; Baas, Matthijs; Nijstad, Bernard A

    2008-05-01

    To understand when and why mood states influence creativity, the authors developed and tested a dual pathway to creativity model; creative fluency (number of ideas or insights) and originality (novelty) are functions of cognitive flexibility, persistence, or some combination thereof. Invoking work on arousal, psychophysiological processes, and working memory capacity, the authors argue that activating moods (e.g., angry, fearful, happy, elated) lead to more creative fluency and originality than do deactivating moods (e.g., sad, depressed, relaxed, serene). Furthermore, activating moods influence creative fluency and originality because of enhanced cognitive flexibility when tone is positive and because of enhanced persistence when tone is negative. Four studies with different mood manipulations and operationalizations of creativity (e.g., brainstorming, category inclusion tasks, gestalt completion tests) support the model.

  7. Possible pathways linking ploidy level to cell elongation and cuticular function in hypocotyls of dark-grown Arabidopsis seedlings

    PubMed Central

    Narukawa, Hideki; Yokoyama, Ryusuke; Nishitani, Kazuhiko

    2016-01-01

    abstract The mechanisms underlying correlations between ploidy level and cell size in eukaryotes remain unclear. Recently, we showed that cell length was higher in tetraploid than in diploid dark-grown Arabidopsis hypocotyls. Cuticular function was aberrant, and expression of genes of cuticle formation was reduced. Here, the links between cell elongation, cuticular function, and ploidy level in the etiolated hypocotyl were examined. Seedlings defective in cuticle formation exhibited shorter hypocotyls. This was due to inhibition of cell elongation rather than cell proliferation, indicating that the reduced cuticular function was a consequence of tetraploidy-induced cell elongation rather than its cause. Inhibition of hypocotyl elongation by impaired cuticles was lower in tetraploid than diploid, indicating that tetraploid hypocotyls were less sensitive to cuticular damage. PMID:26618780

  8. Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence

    PubMed Central

    Krishnan, Neeraja; Gupta, Saurabh; Palve, Vinayak; Varghese, Linu; Pattnaik, Swetansu; Jain, Prach; Khyriem, Costerwell; Hariharan, Arun; Dhas, Kunal; Nair, Jayalakshmi; Pareek, Manisha; Prasad, Venkatesh; Siddappa, Gangotri; Suresh, Amritha; Kekatpure, Vikram; Kuriakose, Moni; Panda, Binay

    2015-01-01

    Oral tongue squamous cell carcinomas (OTSCC) are a homogeneous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs) is on the rise; many of whom lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on single nucleotide variations (SNVs), indels, regions with loss of heterozygosity (LOH), and copy number variations (CNVs) from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including human papilloma virus (HPV) infection and tumor recurrence. Apart from the frequent somatic variants harbored in TP53, CASP8, RASA1, NOTCH and CDKN2A genes, significant amplifications and/or deletions were detected in chromosomes 6-9, and 11 in the tumors. Variants in CASP8 and CDKN2A were mutually exclusive. CDKN2A, PIK3CA, RASA1 and DMD variants were exclusively linked to smoking, chewing, HPV infection and tumor stage. We also performed a whole-genome gene expression study that identified matrix metalloproteases to be highly expressed in tumors and linked pathways involving arachidonic acid and NF-k-B to habits and distant metastasis, respectively. Functional knockdown studies in cell lines demonstrated the role of CASP8 in a HPV-negative OTSCC cell line. Finally, we identified a 38-gene minimal signature that predicts tumor recurrence using an ensemble machine-learning method. Taken together, this study links molecular signatures to various clinical and epidemiological factors in a homogeneous tumor population with a relatively high HPV prevalence. PMID:26834999

  9. Plant Aquaporin AtPIP1;4 Links Apoplastic H2O2 Induction to Disease Immunity Pathways.

    PubMed

    Tian, Shan; Wang, Xiaobing; Li, Ping; Wang, Hao; Ji, Hongtao; Xie, Junyi; Qiu, Qinglei; Shen, Dan; Dong, Hansong

    2016-07-01

    Hydrogen peroxide (H2O2) is a stable component of reactive oxygen species, and its production in plants represents the successful recognition of pathogen infection and pathogen-associated molecular patterns (PAMPs). This production of H2O2 is typically apoplastic but is subsequently associated with intracellular immunity pathways that regulate disease resistance, such as systemic acquired resistance and PAMP-triggered immunity. Here, we elucidate that an Arabidopsis (Arabidopsis thaliana) aquaporin (i.e. the plasma membrane intrinsic protein AtPIP1;4) acts to close the cytological distance between H2O2 production and functional performance. Expression of the AtPIP1;4 gene in plant leaves is inducible by a bacterial pathogen, and the expression accompanies H2O2 accumulation in the cytoplasm. Under de novo expression conditions, AtPIP1;4 is able to mediate the translocation of externally applied H2O2 into the cytoplasm of yeast (Saccharomyces cerevisiae) cells. In plant cells treated with H2O2, AtPIP1;4 functions as an effective facilitator of H2O2 transport across plasma membranes and mediates the translocation of externally applied H2O2 from the apoplast to the cytoplasm. The H2O2-transport role of AtPIP1;4 is essentially required for the cytoplasmic import of apoplastic H2O2 induced by the bacterial pathogen and two typical PAMPs in the absence of induced production of intracellular H2O2 As a consequence, cytoplasmic H2O2 quantities increase substantially while systemic acquired resistance and PAMP-triggered immunity are activated to repress the bacterial pathogenicity. By contrast, loss-of-function mutation at the AtPIP1;4 gene locus not only nullifies the cytoplasmic import of pathogen- and PAMP-induced apoplastic H2O2 but also cancels the subsequent immune responses, suggesting a pivotal role of AtPIP1;4 in apocytoplastic signal transduction in immunity pathways.

  10. Insulin stimulates glucose uptake via a phosphatidylinositide 3-kinase-linked signaling pathway in bovine mammary epithelial cells.

    PubMed

    Zhao, K; Liu, H-Y; Zhou, M-M; Zhao, F-Q; Liu, J-X

    2014-01-01

    The aim of this study was to investigate the effects of insulin on glucose uptake in lactating bovine mammary epithelial cells (BMEC). Primary BMEC were cultured in Dulbecco's modified Eagle's medium/nutrient mixture F-12 and treated with different levels of insulin (0, 5, 50, and 500 ng/mL) for 48 h after a 24-h starvation without fetal calf serum. Compared with the control cells (0 ng of insulin/mL), cell proliferation was enhanced by insulin treatment at all tested levels. Insulin significantly increased glucose uptake at a concentration of 500 ng/mL. In addition, the protein synthesis inhibitor cycloheximide (0.5mg/mL) counteracted the insulin-elevated glucose uptake, thereby suggesting that newly synthesized transporter protein might take part in the insulin-induced glucose uptake. Furthermore, pretreatment of the cells with SB203580, an inhibitor of p38 mitogen-activated protein kinase, did not influence the insulin-induced glucose uptake, but LY294002, a specific inhibitor of phosphatidylinositide 3-kinase, significantly reduced the insulin-stimulated glucose uptake. These results indicated that insulin-induced glucose uptake in BMEC may involve the phosphatidylinositide 3-kinase- but not mitogen-activated protein kinase-mediated signaling pathways.

  11. Indirect CO2 Emission Implications of Energy System Pathways: Linking IO and TIMES Models for the UK.

    PubMed

    Daly, Hannah E; Scott, Kate; Strachan, Neil; Barrett, John

    2015-09-01

    Radical changes to current national energy systems-including energy efficiency and the decarbonization of electricity-will be required in order to meet challenging carbon emission reduction commitments. Technology explicit energy system optimization models (ESOMs) are widely used to define and assess such low-carbon pathways, but these models only account for the emissions associated with energy combustion and either do not account for or do not correctly allocate emissions arising from infrastructure, manufacturing, construction and transport associated with energy technologies and fuels. This paper addresses this shortcoming, through a hybrid approach that estimates the upstream CO2 emissions across current and future energy technologies for the UK using a multiregional environmentally extended input-output model, and explicitly models the direct and indirect CO2 emissions of energy supply and infrastructure technologies within a national ESOM (the UK TIMES model). Results indicate the large significance of nondomestic indirect emissions, particularly coming from fossil fuel imports, and finds that the marginal abatement cost of mitigating all emissions associated with UK energy supply is roughly double that of mitigating only direct emissions in 2050. PMID:26053304

  12. Indirect CO2 Emission Implications of Energy System Pathways: Linking IO and TIMES Models for the UK.

    PubMed

    Daly, Hannah E; Scott, Kate; Strachan, Neil; Barrett, John

    2015-09-01

    Radical changes to current national energy systems-including energy efficiency and the decarbonization of electricity-will be required in order to meet challenging carbon emission reduction commitments. Technology explicit energy system optimization models (ESOMs) are widely used to define and assess such low-carbon pathways, but these models only account for the emissions associated with energy combustion and either do not account for or do not correctly allocate emissions arising from infrastructure, manufacturing, construction and transport associated with energy technologies and fuels. This paper addresses this shortcoming, through a hybrid approach that estimates the upstream CO2 emissions across current and future energy technologies for the UK using a multiregional environmentally extended input-output model, and explicitly models the direct and indirect CO2 emissions of energy supply and infrastructure technologies within a national ESOM (the UK TIMES model). Results indicate the large significance of nondomestic indirect emissions, particularly coming from fossil fuel imports, and finds that the marginal abatement cost of mitigating all emissions associated with UK energy supply is roughly double that of mitigating only direct emissions in 2050.

  13. Studies on synthetic pathway of xylose-containing N-linked oligosaccharides deduced from substrate specificities of the processing enzymes in sycamore cells (Acer pseudoplatanus L.).

    PubMed

    Tezuka, K; Hayashi, M; Ishihara, H; Akazawa, T; Takahashi, N

    1992-02-01

    We measured the activities of alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase, alpha-1,6-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase, beta-1,4-mannosyl-glycoprotein beta-1,2-xylosyltransferase and glycoprotein 3-alpha-L-fucosyltransferase in the Golgi fraction of suspension-cultured cells of sycamore (Acer pseudoplatanus L.) using fluorescence-labelled oligosaccharides as acceptor substrates for these transferase reactions. The structures of the pyridylaminated oligosaccharides produced by these reactions were analyzed by two-dimensional sugar mapping using high-performance liquid chromatography. We demonstrated that (formula; see text) was processed to produce by these in vitro reactions. On the basis of these results, we discuss a biosynthetic pathway for xylose containing N-linked oligosaccharides in plant glycoproteins.

  14. Integrin-linked kinase affects signaling pathways and migration in thyroid cancer cells and is a potential therapeutic target

    PubMed Central

    Shirley, Lawrence A.; McCarty, Samantha; Yang, Ming-Chen; Saji, Motoyasu; Zhang, Xiaoli; Phay, John; Ringel, Matthew D.; Chen, Ching-Shih

    2016-01-01

    Background Integrin-linked kinase (ILK) is a serine-threonine kinase that regulates interactions between the cell and the extracellular matrix. In many cancers, overexpression of ILK leads to increased cell proliferation, motility, and invasion. We hypothesized that ILK functions as a regulator of viability and migration in thyroid cancer cells. Methods Eleven human thyroid cancer cell lines were screened for ILK protein expression. The cell lines with the greatest expression were treated with either ILK small interfering RNA (siRNA) or a novel ILK inhibitor, T315, and the effects were evaluated via Western blot and migration assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assays were performed to assess cell viability. Results siRNA against ILK decreased phosphorylation of downstream effectors Akt and MLC, as well as decreased migration. Treatment with T315 showed a dose-related decrease in both Akt and MLC phosphorylation, as well as decreased migration. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assays showed T315 to have an half maximal inhibitory concentration of less than 1 µM in cell lines with high ILK expression. Conclusion ILK is expressed differentially in thyroid cancer cell lines. Both ILK siRNA and T315 inhibit motility of thyroid cancer cell lines, and T315 is shown to be cytotoxic at low concentrations. Altogether, our study suggests that ILK may represent an important kinase in aggressive thyroid cancers. PMID:26549818

  15. The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner

    PubMed Central

    Bammler, Theodor K.; Beyer, Richard P.; Churchwell, Mona; Doerge, Daniel R.; Meira, Lisiane B.; Palmer, Valerie S.; Ramos-Crawford, Ana-Luiza; Ren, Xuefeng; Sullivan, Robert C.; Kavanagh, Terrance J.; Samson, Leona D.; Zarbl, Helmut

    2011-01-01

    Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of adult C57BL6 wild-type mice treated with a single systemic dose of MAM acetate display DNA damage (O6-methyldeoxyguanosine lesions, O6-mG) that remains constant up to 7 days post-treatment. By contrast, MAM-treated mice lacking a functional gene encoding the DNA repair enzyme O6-mG DNA methyltransferase (MGMT) showed elevated O6-mG DNA damage starting at 48 hours post-treatment. The DNA damage was linked to changes in the expression of genes in cell-signaling pathways associated with cancer, human neurodegenerative disease, and neurodevelopmental disorders. These data are consistent with the established developmental neurotoxic and carcinogenic properties of MAM in rodents. They also support the hypothesis that early-life exposure to MAM-glucoside (cycasin) has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for food or medicine, or both. These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer) or not (neurodegeneration). Exposure to MAM-related environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer's disease. PMID:21731631

  16. Interaction between small GTPase Rab7 and PI3KC3 links autophagy and endocytosis: A new Rab7 effector protein sheds light on membrane trafficking pathways.

    PubMed

    Lin, Mary Grace; Zhong, Qing

    2011-03-01

    Endocytosis and autophagy are both membrane trafficking pathways vital for cell survival. Endocytosis, the primary means by which cells internalize material such as cell-surface receptors and their protein ligands, is essential for proper cell growth and communication. Autophagy is a catabolic process that degrades cargo ranging from organelles to protein aggregates to bacteria, and it is important for maintaining cellular homeostasis. Defects in both endosome and autophagosome maturation lead to an array of human diseases, including cancer; however, the molecular mechanisms underlying endosome and autophagosome maturation are not well characterized. In the case of endocytosis, small GTPases, key players in membrane organization, are required for endosome maturation. Specifically, activation of the small GTPase Rab7 is required for the initiation of the early-to-late endosome transition, although how this is regulated is largely unknown. Now recent findings from our laboratory show that Rubicon, a component of the PI3KC3 complex, inhibits endosome maturation by preventing activation of Rab7. Not only do our results clarify the molecular link between PI3KC3 and Rab7 function in endosome maturation, they lead us to propose new models for PI3KC3 involvement in membrane trafficking, particularly at the convergence between the endosome and autophagosome pathways.

  17. PRO40 is a scaffold protein of the cell wall integrity pathway, linking the MAP kinase module to the upstream activator protein kinase C.

    PubMed

    Teichert, Ines; Steffens, Eva Katharina; Schnaß, Nicole; Fränzel, Benjamin; Krisp, Christoph; Wolters, Dirk A; Kück, Ulrich

    2014-09-01

    Mitogen-activated protein kinase (MAPK) pathways are crucial signaling instruments in eukaryotes. Most ascomycetes possess three MAPK modules that are involved in key developmental processes like sexual propagation or pathogenesis. However, the regulation of these modules by adapters or scaffolds is largely unknown. Here, we studied the function of the cell wall integrity (CWI) MAPK module in the model fungus Sordaria macrospora. Using a forward genetic approach, we found that sterile mutant pro30 has a mutated mik1 gene that encodes the MAPK kinase kinase (MAPKKK) of the proposed CWI pathway. We generated single deletion mutants lacking MAPKKK MIK1, MAPK kinase (MAPKK) MEK1, or MAPK MAK1 and found them all to be sterile, cell fusion-deficient and highly impaired in vegetative growth and cell wall stress response. By searching for MEK1 interaction partners via tandem affinity purification and mass spectrometry, we identified previously characterized developmental protein PRO40 as a MEK1 interaction partner. Although fungal PRO40 homologs have been implicated in diverse developmental processes, their molecular function is currently unknown. Extensive affinity purification, mass spectrometry, and yeast two-hybrid experiments showed that PRO40 is able to bind MIK1, MEK1, and the upstream activator protein kinase C (PKC1). We further found that the PRO40 N-terminal disordered region and the central region encompassing a WW interaction domain are sufficient to govern interaction with MEK1. Most importantly, time- and stress-dependent phosphorylation studies showed that PRO40 is required for MAK1 activity. The sum of our results implies that PRO40 is a scaffold protein for the CWI pathway, linking the MAPK module to the upstream activator PKC1. Our data provide important insights into the mechanistic role of a protein that has been implicated in sexual and asexual development, cell fusion, symbiosis, and pathogenicity in different fungal systems.

  18. The Nuclear Factor kappaB Pathway: A Link to the Immune System in the Radiation Response

    NASA Astrophysics Data System (ADS)

    Hellweg, Christine; Baumstark-Khan, Christa; Reitz, Guenther; Chishti, Arif Ali; Koch, Kristina; Manchanda, Kashish

    Understanding the cellular radiation response is an essential prerequisite for the risk assessment of astronauts’ space radiation exposure during long-term space missions and for effective countermeasure development. In addition to the space radiation effects, other environmental factors during space missions such as microgravity have profound effects on the body, e.g. suppression of the innate and acquired immune response. Exposure to ionizing radiation modulates immune responses in a complex dose-dependent pattern, with possible anti-inflammatory effects in the low dose range, expression of pro-inflammatory cytokines at moderate doses and immunosuppression after exposure to higher doses due to precursor cell death together with concomitant exacerbated innate immune responses. A central regulator in the immune system is the transcription factor Nuclear Factor kB (NF-kappaB). In this work, the role of NF-kappaB in the cellular response to space relevant radiation qualities was analyzed. It was shown with a recombinant human NF-kappaB reporter cell line that heavy ions with a linear energy transfer (LET) of 100-300 keV/µm have a nine times higher potential to activate the NF-kappaB pathway compared to X-rays (150 kV). ATM was essential for NF-kappaB activation in response to X-rays and heavy ions. Knockdown of the NF-kappaB subunit RelA (p65) resulted in higher sensitivity towards X-rays. Reverse Transcriptase real-time quantitative PCR (RT-qPCR) experiments showed that after exposure to radiation, NF-kappaB predominantly upregulates genes involved in intercellular communication processes, especially genes coding for chemokines, suggesting an important contribution of NF-kappaB in the molecular profile of the reaction to radiation, which can comprise features of inflammation and wound healing processes. This is process is strictly NF-kappaB dependent as this response is completely absent in RelA knockdown cells. These results show that the role of NF-kappaB in

  19. Changes in O-Linked N-Acetylglucosamine (O-GlcNAc) Homeostasis Activate the p53 Pathway in Ovarian Cancer Cells.

    PubMed

    de Queiroz, Rafaela Muniz; Madan, Rashna; Chien, Jeremy; Dias, Wagner Barbosa; Slawson, Chad

    2016-09-01

    O-GlcNAcylation is a dynamic post-translational modification consisting of the addition of a single N-acetylglucosamine sugar to serine and threonine residues in proteins by the enzyme O-linked β-N-acetylglucosamine transferase (OGT), whereas the enzyme O-GlcNAcase (OGA) removes the modification. In cancer, tumor samples present with altered O-GlcNAcylation; however, changes in O-GlcNAcylation are not consistent between tumor types. Interestingly, the tumor suppressor p53 is modified by O-GlcNAc, and most solid tumors contain mutations in p53 leading to the loss of p53 function. Because ovarian cancer has a high frequency of p53 mutation rates, we decided to investigate the relationship between O-GlcNAcylation and p53 function in ovarian cancer. We measured a significant decrease in O-GlcNAcylation of tumor tissue in an ovarian tumor microarray. Furthermore, O-GlcNAcylation was increased, and OGA protein and mRNA levels were decreased in ovarian tumor cell lines not expressing the protein p53. Treatment with the OGA inhibitor Thiamet-G (TMG), silencing of OGA, or overexpression of OGA and OGT led to p53 stabilization, increased nuclear localization, and increased protein and mRNA levels of p53 target genes. These data suggest that changes in O-GlcNAc homeostasis activate the p53 pathway. Combination treatment of the chemotherapeutic cisplatin with TMG decreased tumor cell growth and enhanced cell cycle arrest without impairing cytotoxicity. The effects of TMG on tumor cell growth were partially dependent on wild type p53 activation. In conclusion, changes in O-GlcNAc homeostasis activate the wild type p53 pathway in ovarian cancer cells, and OGA inhibition has the potential as an adjuvant treatment for ovarian carcinoma. PMID:27402830

  20. Changes in O-Linked N-Acetylglucosamine (O-GlcNAc) Homeostasis Activate the p53 Pathway in Ovarian Cancer Cells.

    PubMed

    de Queiroz, Rafaela Muniz; Madan, Rashna; Chien, Jeremy; Dias, Wagner Barbosa; Slawson, Chad

    2016-09-01

    O-GlcNAcylation is a dynamic post-translational modification consisting of the addition of a single N-acetylglucosamine sugar to serine and threonine residues in proteins by the enzyme O-linked β-N-acetylglucosamine transferase (OGT), whereas the enzyme O-GlcNAcase (OGA) removes the modification. In cancer, tumor samples present with altered O-GlcNAcylation; however, changes in O-GlcNAcylation are not consistent between tumor types. Interestingly, the tumor suppressor p53 is modified by O-GlcNAc, and most solid tumors contain mutations in p53 leading to the loss of p53 function. Because ovarian cancer has a high frequency of p53 mutation rates, we decided to investigate the relationship between O-GlcNAcylation and p53 function in ovarian cancer. We measured a significant decrease in O-GlcNAcylation of tumor tissue in an ovarian tumor microarray. Furthermore, O-GlcNAcylation was increased, and OGA protein and mRNA levels were decreased in ovarian tumor cell lines not expressing the protein p53. Treatment with the OGA inhibitor Thiamet-G (TMG), silencing of OGA, or overexpression of OGA and OGT led to p53 stabilization, increased nuclear localization, and increased protein and mRNA levels of p53 target genes. These data suggest that changes in O-GlcNAc homeostasis activate the p53 pathway. Combination treatment of the chemotherapeutic cisplatin with TMG decreased tumor cell growth and enhanced cell cycle arrest without impairing cytotoxicity. The effects of TMG on tumor cell growth were partially dependent on wild type p53 activation. In conclusion, changes in O-GlcNAc homeostasis activate the wild type p53 pathway in ovarian cancer cells, and OGA inhibition has the potential as an adjuvant treatment for ovarian carcinoma.

  1. optix functions as a link between the retinal determination network and the dpp pathway to control morphogenetic furrow progression in Drosophila

    PubMed Central

    Li, Yumei; Jiang, Yuwei; Chen, Yiyun; Karandikar, Umesh; Hoffman, Kristi; Chattopadhyay, Abanti; Mardon, Graeme; Chen, Rui

    2013-01-01

    optix, the Drosophila ortholog of the SIX3/6 gene family in vertebrate, encodes a homeodomain protein with a SIX protein-protein interaction domain. In vertebrates, Six3/6 genes are required for normal eye as well as brain development. However, the normal function of optix in Drosophila remains unknown due to lack of loss-of-function mutation. Previous studies suggest that optix is likely to play important role as part of the retinal determination (RD) network. To elucidate normal optix function during retinal development, multiple null alleles for optix have been generated. Loss-of-function mutations in optix result in lethality at the pupae stage. Surprisingly, close examination of its function during eye development reveals that, unlike other members of the RD network, optix is required only for morphogenetic furrow (MF) progression, but not initiation. The mechanisms by which optix regulates MF progression is likely through regulation of signaling molecules in the furrow. Specifically, although unaffected during MF initiation, expression of dpp in the MF is dramatically reduced in optix mutant clones. In parallel, we find that optix is regulated by sine oculis and eyes absent, key members of the RD network. Furthermore, positive feedback between optix and sine oculis and eyes absent is observed, which is likely mediated through dpp signaling pathway. Together with the observation that optix expression does not depend on hh or dpp, we propose that optix functions together with hh to regulate dpp in the MF, serving as a link between the RD network and the patterning pathways controlling normal retinal development. PMID:23792115

  2. Clusterin and the terminal complement pathway synthesized by human umbilical vein endothelial cells are closely linked when detected on co-cultured agarose beads.

    PubMed

    Berge, V; Johnson, E; Høgåsen, K

    1997-01-01

    Clusterin and the terminal complement pathway synthesized by human umbilical vein endothelial cells are closely linked when detected on co-cultured agarose beads. Clusterin is a multifunctional regulatory protein rendering the terminal complement complex (TCC) soluble and unable to insert into cell membranes. The aim of the present study was to examine whether clusterin was an integral part of serum-derived TCC bound to agarose beads which activate the alternative pathway of complement. Further, we searched for evidence of clusterin synthesis in human umbilical vein endothelial cells (EC) and whether this synthesis was regulated by various proinflammatory cytokines (IL-1, IL-6, and TNF) and IFN-gamma. The clusterin and TCC on co-incubated beads were measured by radioimmunoassay based on primary anti-complement antibodies (anti-C3c, anti-TCC, anti-clusterin). We found that clusterin in serum experiments is bound to C9 in agarose bound TCC and not directly to the agarose. Addition of the protein synthesis inhibitor cycloheximide to cultured human umbilical vein cells resulted in a strong reduction (about 70%) of anti-clusterin binding to co-cultured beads, which strongly supports de novo synthesis of clusterin in EC. The results indicate that clusterin derived from the EC is linked with the TCC on the co-incubated beads for the following reasons: First, in serum experiments clusterin like vitronectin, was co-deposited with C9 in agarose-bound TCC. Second, cytokine stimulation of the EC with proinflammatory cytokines such as IL-1, IL-6 and TNF, known to increase the detection of bound TCC, also increased the amount of clusterin detected on the beads. Third, IFN-gamma, which reduces the concentration of bound TCC, exhibited the same effect on the amount of clusterin detected on such beads. There was a strong and dose-dependent reduction of anti-TCC binding from about 45% to about 95% when clusterin (5-40 micrograms/ml) was added to EC cultures. This effect was also

  3. SARS Coronavirus Papain-Like Protease Inhibits the TLR7 Signaling Pathway through Removing Lys63-Linked Polyubiquitination of TRAF3 and TRAF6

    PubMed Central

    Li, Shih-Wen; Wang, Ching-Ying; Jou, Yu-Jen; Huang, Su-Hua; Hsiao, Li-Hsin; Wan, Lei; Lin, Ying-Ju; Kung, Szu-Hao; Lin, Cheng-Wen

    2016-01-01

    Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. TLR7 agonist (imiquimod (IMQ)) concentration-dependently induced activation of ISRE-, NF-κB- and AP-1-luciferase reporters, as well as the production of IFN-α, IFN-β, TNF-α, IL-6 and IL-8 in human promonocyte cells. However, SARS-CoV PLPro significantly inhibited IMQ-induced cytokine production through suppressing the activation of transcription factors IRF-3, NF-κB and AP-1. Western blot analysis with anti-Lys48 and anti-Lys63 ubiquitin antibodies indicated the SARS-CoV PLPro removed Lys63-linked ubiquitin chains of TRAF3 and TRAF6, but not Lys48-linked ubiquitin chains in un-treated and treated cells. The decrease in the activated state of TRAF3 and TRAF6 correlated with the inactivation of TBK1 in response to IMQ by PLPro. The results revealed that the antagonism of SARS-CoV PLPro on TLR7-mediated innate immunity was associated with the negative regulation of TRAF3/6-TBK1-IRF3/NF-κB/AP1 signals. PMID:27164085

  4. SARS Coronavirus Papain-Like Protease Inhibits the TLR7 Signaling Pathway through Removing Lys63-Linked Polyubiquitination of TRAF3 and TRAF6.

    PubMed

    Li, Shih-Wen; Wang, Ching-Ying; Jou, Yu-Jen; Huang, Su-Hua; Hsiao, Li-Hsin; Wan, Lei; Lin, Ying-Ju; Kung, Szu-Hao; Lin, Cheng-Wen

    2016-01-01

    Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. TLR7 agonist (imiquimod (IMQ)) concentration-dependently induced activation of ISRE-, NF-κB- and AP-1-luciferase reporters, as well as the production of IFN-α, IFN-β, TNF-α, IL-6 and IL-8 in human promonocyte cells. However, SARS-CoV PLPro significantly inhibited IMQ-induced cytokine production through suppressing the activation of transcription factors IRF-3, NF-κB and AP-1. Western blot analysis with anti-Lys48 and anti-Lys63 ubiquitin antibodies indicated the SARS-CoV PLPro removed Lys63-linked ubiquitin chains of TRAF3 and TRAF6, but not Lys48-linked ubiquitin chains in un-treated and treated cells. The decrease in the activated state of TRAF3 and TRAF6 correlated with the inactivation of TBK1 in response to IMQ by PLPro. The results revealed that the antagonism of SARS-CoV PLPro on TLR7-mediated innate immunity was associated with the negative regulation of TRAF3/6-TBK1-IRF3/NF-κB/AP1 signals. PMID:27164085

  5. Socioeconomic status and structural brain development.

    PubMed

    Brito, Natalie H; Noble, Kimberly G

    2014-01-01

    Recent advances in neuroimaging methods have made accessible new ways of disentangling the complex interplay between genetic and environmental factors that influence structural brain development. In recent years, research investigating associations between socioeconomic status (SES) and brain development have found significant links between SES and changes in brain structure, especially in areas related to memory, executive control, and emotion. This review focuses on studies examining links between structural brain development and SES disparities of the magnitude typically found in developing countries. We highlight how highly correlated measures of SES are differentially related to structural changes within the brain.

  6. Socioeconomic status and structural brain development

    PubMed Central

    Brito, Natalie H.; Noble, Kimberly G.

    2014-01-01

    Recent advances in neuroimaging methods have made accessible new ways of disentangling the complex interplay between genetic and environmental factors that influence structural brain development. In recent years, research investigating associations between socioeconomic status (SES) and brain development have found significant links between SES and changes in brain structure, especially in areas related to memory, executive control, and emotion. This review focuses on studies examining links between structural brain development and SES disparities of the magnitude typically found in developing countries. We highlight how highly correlated measures of SES are differentially related to structural changes within the brain. PMID:25249931

  7. Socioeconomic status and structural brain development.

    PubMed

    Brito, Natalie H; Noble, Kimberly G

    2014-01-01

    Recent advances in neuroimaging methods have made accessible new ways of disentangling the complex interplay between genetic and environmental factors that influence structural brain development. In recent years, research investigating associations between socioeconomic status (SES) and brain development have found significant links between SES and changes in brain structure, especially in areas related to memory, executive control, and emotion. This review focuses on studies examining links between structural brain development and SES disparities of the magnitude typically found in developing countries. We highlight how highly correlated measures of SES are differentially related to structural changes within the brain. PMID:25249931

  8. A Kinase Anchoring Protein 9 Is a Novel Myosin VI Binding Partner That Links Myosin VI with the PKA Pathway in Myogenic Cells.

    PubMed

    Karolczak, Justyna; Sobczak, Magdalena; Skowronek, Krzysztof; Rędowicz, Maria Jolanta

    2015-01-01

    Myosin VI (MVI) is a unique motor protein moving towards the minus end of actin filaments unlike other known myosins. Its important role has recently been postulated for striated muscle and myogenic cells. Since MVI functions through interactions of C-terminal globular tail (GT) domain with tissue specific partners, we performed a search for MVI partners in myoblasts and myotubes using affinity chromatography with GST-tagged MVI-GT domain as a bait. A kinase anchoring protein 9 (AKAP9), a regulator of PKA activity, was identified by means of mass spectrometry as a possible MVI interacting partner both in undifferentiated and differentiating myoblasts and in myotubes. Coimmunoprecipitation and proximity ligation assay confirmed that both proteins could interact. MVI and AKAP9 colocalized at Rab5 containing early endosomes. Similarly to MVI, the amount of AKAP9 decreased during myoblast differentiation. However, in MVI-depleted cells, both cAMP and PKA levels were increased and a change in the MVI motor-dependent AKAP9 distribution was observed. Moreover, we found that PKA phosphorylated MVI-GT domain, thus implying functional relevance of MVI-AKAP9 interaction. We postulate that this novel interaction linking MVI with the PKA pathway could be important for targeting AKAP9-PKA complex within cells and/or providing PKA to phosphorylate MVI tail domain.

  9. Socioeconomic trends in radiology.

    PubMed

    Barneveld Binkhuysen, F H

    1998-01-01

    For radiology the socioeconomic environment is a topic of increasing importance. In addition to the well-known important scientific developments in radiology such as interventional MRI, several other major trends can be recognized: (1) changes in the delivery of health care, in which all kinds of managed care are developing and will influence the practice of radiology, and (2) the process of computerization and digitization. The socioeconomic environment of radiology will be transformed by the developments in managed care, teleradiology and the integration of information systems. If radiologists want to manage future radiology departments they must have an understanding of the changes in the fields of economics and politics that are taking place and that will increasingly influence radiology. Some important and recognizable aspects of these changes will be described here. PMID:9477292

  10. Malaria Infection, Poor Nutrition and Indoor Air Pollution Mediate Socioeconomic Differences in Adverse Pregnancy Outcomes in Cape Coast, Ghana

    PubMed Central

    Amegah, Adeladza K.; Damptey, Obed K.; Sarpong, Gideon A.; Duah, Emmanuel; Vervoorn, David J.; Jaakkola, Jouni J. K.

    2013-01-01

    Background The epidemiological evidence linking socioeconomic deprivation with adverse pregnancy outcomes has been conflicting mainly due to poor measurement of socioeconomic status (SES). Studies have also failed to evaluate the plausible pathways through which socioeconomic disadvantage impacts on pregnancy outcomes. We investigated the importance of maternal SES as determinant of birth weight and gestational duration in an urban area and evaluated main causal pathways for the influence of SES. Methods A population-based cross-sectional study was conducted among 559 mothers accessing postnatal services at the four main health facilities in Cape Coast, Ghana in 2011. Information on socioeconomic characteristics of the mothers was collected in a structured questionnaire. Results In multivariate linear regression adjusting for maternal age, parity and gender of newborn, low SES resulted in 292 g (95% CI: 440–145) reduction in birth weight. Important SES-related determinants were neighborhood poverty (221 g; 95% CI: 355–87), low education (187 g; 95% CI: 355–20), studentship during pregnancy (291 g; 95% CI: 506–76) and low income (147 g; 95% CI: 277–17). In causal pathway analysis, malaria infection (6–20%), poor nutrition (2–51%) and indoor air pollution (10–62%) mediated substantial proportions of the observed effects of socioeconomic deprivation on birth weight. Generalized linear models adjusting for confounders indicated a 218% (RR: 3.18; 95% CI: 1.41–7.21) risk increase of LBW and 83% (RR: 1.83; 95% CI: 1.31–2.56) of PTB among low income mothers. Low and middle SES was associated with 357% (RR: 4.57; 95% CI: 1.67–12.49) and 278% (RR: 3.78; 95% CI: 1.39–10.27) increased risk of LBW respectively. Malaria infection, poor nutrition and indoor air pollution respectively mediated 10–21%, 16–44% and 31–52% of the observed effects of socioeconomic disadvantage on LBW risk. Conclusion We provide evidence of the effects of socioeconomic

  11. Socioeconomic Disparities in the Seroprevalence of Cytomegalovirus Infection in the U.S. Population: NHANES III

    PubMed Central

    Dowd, J.B.; Aiello, A.E.; Alley, D.E.

    2013-01-01

    Summary There is a strong relationship between socioeconomic status (SES) and health outcomes in the U.S, though the mechanisms are poorly understood. Increasing evidence points to links between lifelong exposure to infectious disease and subsequent chronic disease. Exposure and susceptibility to infections may be one way SES affects long-term health, though little population-based research to date has examined social patterning of infections in the U.S. This paper tests the relationship between income, education, race/ethnicity and seroprevalence of cytomegalovirus (CMV) infection at different ages in a representative sample of the U.S. population, and tests potential mediators for these relationships. The study finds significant racial and socioeconomic disparities in CMV seroprevalence beginning at early ages and persisting into middle age. Potential exposures do not explain the relationship between socioeconomic status and CMV positivity. Because reactivation of latent CMV infections may contribute to chronic disease and immune decline later in life, future research should determine the exposure or susceptibility pathways responsible for these disparities in the prevalence of CMV infection. PMID:18413004

  12. Evolution of MIR159/319 microRNA genes and their post-transcriptional regulatory link to siRNA pathways

    PubMed Central

    2011-01-01

    -transcriptional level to express multiple mature products with variable proportions under different circumstances. Moreover, our analyses reveal conserved regulatory link of MIR159/319 genes to siRNA pathway through post-transcriptional regulation. PMID:21569383

  13. The link between cell-cycle dependent radiosensitivity and repair pathways: a model based on the local, sister-chromatid conformation dependent switch between NHEJ and HR.

    PubMed

    Hufnagl, Antonia; Herr, Lisa; Friedrich, Thomas; Durante, Marco; Taucher-Scholz, Gisela; Scholz, Michael

    2015-03-01

    The different DNA damage repair pathways like homologous recombination (HR) and non-homologous end joining (NHEJ) have been linked to the variation of radiosensitivity throughout the cell cycle. However, no attempts have been made to test the various hypotheses derived from these studies in a quantitative way e.g. by using modeling approaches. Here we present the first modeling approach that allows predicting the cell cycle dependent radiosensitivity of repair proficient as well as of repair deficient cell lines after photon irradiation based on a small set of parameters and assumptions. A key element of the model is the classification of DNA damage according to its complexity on the level of chromatin loops of about 2Mbp size. Isolated DSB (iDSB), characterized by a single DSB within a chromatin loop, are distinguished from clustered DSB (cDSB), characterized by two or more DSB within a chromatin loop. The class of iDSB is further subdivided into two sub-classes, characterized by the replication status of the corresponding chromatin loop. For iDSB in replicated loops that are in close contact, error-free homologous recombination is assumed to be effective; in unreplicated loops or in replicated loops that have already been separated, iDSB are assumed to be repaired by error-prone non-homologous end joining. cDSB are assumed not to be repairable effectively by neither HR nor NHEJ. Assigning empirically derived lethalities to these three damage classes and pathways, we demonstrate that the model is able to accurately reproduce cell cycle dependent survival probabilities. Notably, the relevant parameters are derived solely from two survival curves for normal, repair proficient cells in G1 and late-S phase. Based on a comparison of model predictions with a large data set reported in the literature, we show that the lethality values for wild type cells are simultaneously predictive for the cell cycle dependent variation of sensitivity observed for HR-deficient and NHEJ

  14. Socioeconomic Position and Inflammatory and Immune Biomarkers of Cardiovascular Disease: Applications to the Panel Study of Income Dynamics

    PubMed Central

    Aiello, Allison E.; Kaplan, George A.

    2012-01-01

    Biomarkers are an important aspect of research linking psychosocial stress and health. This paper aims to characterize the biological pathways that may mediate the relationship between socioeconomic position (SEP) and cardiovascular disease (CVD) and address opportunities for further research within the Panel Study for Income Dynamics (PSID), with a focus on psychosocial stressors related to SEP. We review the literature on CVD biomarkers, including adhesion and proinflammatory molecules (IL-6, other cytokines, C-reactive proteins, fibrinogen, etc.) and microbial pathogens. The impact of socioeconomic determinants and related psychosocial stressors on CVD biomarkers mediated by behavioral and central nervous system pathways are described. We also address measurement and feasibility issues including: specimen collection methods, processing and storage procedures, laboratory error, and within-person variability. In conclusion, we suggest that PSID consider adding important assessments of specific CVD biomarkers and mediating behavioral measures, health, and medications that will ultimately address many of the gaps in the literature regarding the relationship between socioeconomic position and cardiovascular health. PMID:20183904

  15. Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression

    PubMed Central

    Saeed, Muhammad Tariq; Holowatyj, Andreana N.; Sheikh, Iftikhar A.; Zafar Paracha, Rehan; Shafi, Aamir; Siddiqa, Amnah; Bibi, Zurah; Khan, Mukaram

    2016-01-01

    The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. However, the association between hyper-O-GlcNAcylation and activation of these oncogenes remains poorly characterized. Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. We compute delay constraints to reveal important associations between the production and degradation rates of proteins. O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer. PMID:27703839

  16. Acquisition of epithelial-mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway.

    PubMed

    Wang, Zhiwei; Li, Yiwei; Kong, Dejuan; Banerjee, Sanjeev; Ahmad, Aamir; Azmi, Asfar Sohail; Ali, Shadan; Abbruzzese, James L; Gallick, Gary E; Sarkar, Fazlul H

    2009-03-15

    Despite rapid advances in many fronts, pancreatic cancer (PC) remains one of the most difficult human malignancies to treat due, in part, to de novo and acquired chemoresistance and radioresistance. Gemcitabine alone or in combination with other conventional therapeutics is the standard of care for the treatment of advanced PC without any significant improvement in the overall survival of patients diagnosed with this deadly disease. Previous studies have shown that PC cells that are gemcitabine-resistant (GR) acquired epithelial-mesenchymal transition (EMT) phenotype, which is reminiscent of "cancer stem-like cells"; however, the molecular mechanism that led to EMT phenotype has not been fully investigated. The present study shows that Notch-2 and its ligand, Jagged-1, are highly up-regulated in GR cells, which is consistent with the role of the Notch signaling pathway in the acquisition of EMT and cancer stem-like cell phenotype. We also found that the down-regulation of Notch signaling was associated with decreased invasive behavior of GR cells. Moreover, down-regulation of Notch signaling by siRNA approach led to partial reversal of the EMT phenotype, resulting in the mesenchymal-epithelial transition, which was associated with decreased expression of vimentin, ZEB1, Slug, Snail, and nuclear factor-kappaB. These results provide molecular evidence showing that the activation of Notch signaling is mechanistically linked with chemoresistance phenotype (EMT phenotype) of PC cells, suggesting that the inactivation of Notch signaling by novel strategies could be a potential targeted therapeutic approach for overcoming chemoresistance toward the prevention of tumor progression and/or treatment of metastatic PC.

  17. Contributions of neuroscience to the study of socioeconomic health disparities

    PubMed Central

    Gianaros, Peter J.; Hackman, Daniel

    2013-01-01

    Socioeconomic disadvantage confers risk for ill health. Historically, the pathways by which socioeconomic disadvantage may affect health have been viewed from epidemiological perspectives emphasizing environmental, behavioral, and biopsychosocial risk factors. Such perspectives, however, have yet to integrate findings from emerging neuroscience studies demonstrating that indicators of socioeconomic disadvantage relate to patterns of brain morphology and functionality that have been associated with aspects of mental, physical, and cognitive health over the lifecourse. This commentary considers findings from one such study appearing in the current issue of Psychosomatic Medicine. It reports that an area-level indicator of socioeconomic disadvantage relates to cortical morphology in brain regions important for language, executive control, and other cognitive and behavioral functions—possibly via a systemic inflammatory pathway. These findings are put into context by discussing broader questions and challenges that need to be addressed in order for neuroscience approaches to (i) become better integrated with existing epidemiological perspectives and (ii) more fully advance our understanding of the pathways by which socioeconomic disadvantage becomes embodied by the brain in relation to health. PMID:23975944

  18. Socioeconomic status, schooling, and the developmental trajectories of adolescents.

    PubMed

    Crosnoe, Robert; Huston, Aletha C

    2007-09-01

    The socioeconomic stratification of American society profoundly influences how the life course unfolds by shaping various developmental pathways as well as the connections among these pathways. Drawing on a nationally representative sample of American adolescents, this study charted trajectories of personal control and parental consultation from middle school to the end of high school and then examined how various combinations of these trajectories were associated with math/science course taking in high school across socioeconomic strata. Results indicated that low and/or decreasing levels of personal control were associated with the accumulation of fewer math/science credits, as were declining levels of parental consultation no matter what the initial level. Mismatches between control and consultation trajectories (e.g., high, stable control with low, stable consultation) were also associated with fewer math/science credits. These patterns tended to be less predictive of math/science credit accumulation at the highest and lowest ends of the socioeconomic spectrum. PMID:17723038

  19. A three-tiered approach for linking pharmacokinetic considerations to the adverse outcome pathway framework for chemical-specific risk assessment

    EPA Science Inventory

    The power of the adverse outcome pathway (AOP) framework arises from its utilization of pathway-based data to describe the initial interaction of a chemical with a molecular target (molecular initiating event; (MIE), followed by a progression through a series of key events that l...

  20. The PDZ Protein Canoe/AF-6 Links Ras-MAPK, Notch and Wingless/Wnt Signaling Pathways by Directly Interacting with Ras, Notch and Dishevelled

    PubMed Central

    Carmena, Ana; Speicher, Stephan; Baylies, Mary

    2006-01-01

    Over the past few years, it has become increasingly apparent that signal transduction pathways are not merely linear cascades; they are organized into complex signaling networks that require high levels of regulation to generate precise and unique cell responses. However, the underlying regulatory mechanisms by which signaling pathways cross-communicate remain poorly understood. Here we show that the Ras-binding protein Canoe (Cno)/AF-6, a PDZ protein normally associated with cellular junctions, is a key modulator of Wingless (Wg)/Wnt, Ras-Mitogen Activated Protein Kinase (MAPK) and Notch (N) signaling pathways cross-communication. Our data show a repressive effect of Cno/AF-6 on these three signaling pathways through physical interactions with Ras, N and the cytoplasmic protein Dishevelled (Dsh), a key Wg effector. We propose a model in which Cno, through those interactions, actively coordinates, at the membrane level, Ras-MAPK, N and Wg signaling pathways during progenitor specification. PMID:17183697

  1. Learning Motivation Mediates Gene-by-Socioeconomic Status Interaction on Mathematics Achievement in Early Childhood

    ERIC Educational Resources Information Center

    Tucker-Drob, Elliot M.; Harden, K. Paige

    2012-01-01

    There is accumulating evidence that genetic influences on achievement are more pronounced among children living in higher socioeconomic status homes, and that these gene-by-environment interactions occur prior to children's entry into formal schooling. We hypothesized that one pathway through which socioeconomic status promotes genetic influences…

  2. The Relationship between Socioeconomic Status and Counseling Outcomes

    ERIC Educational Resources Information Center

    Hawley, Lisa D.; Leibert, Todd W.; Lane, Joel A.

    2014-01-01

    In this study, we examined the relationship between various indices of socioeconomic status (SES) and counseling outcomes among clients at a university counseling center. We also explored links between SES and three factors that are generally regarded as facilitative of client change in counseling: motivation, treatment expectancy and social…

  3. Explaining the Socio-Economic Status School Completion Gap

    ERIC Educational Resources Information Center

    Polidano, Cain; Hanel, Barbara; Buddelmeyer, Hielke

    2013-01-01

    Relatively low rates of school completion among students from low socio-economic backgrounds is a key driver of intergenerational inequality. Linking data from the Programme for International Student Assessment with data from the Longitudinal Survey of Australian Youth, we use a decomposition framework to explain the gap in school completion rates…

  4. Socio-Economic Status and Language Acquisition: Children's Performance on the New Reynell Developmental Language Scales

    ERIC Educational Resources Information Center

    Letts, Carolyn; Edwards, Susan; Sinka, Indra; Schaefer, Blanca; Gibbons, Wendy

    2013-01-01

    Background: Several studies in recent years have indicated a link between socio-economic status (SES) of families and children's language development, including studies that have measured children's language through formal standardized test procedures. High numbers of children with low performance have been found in lower socio-economic groups in…

  5. Socioeconomic Status and Financial Coping Strategies: The Mediating Role of Perceived Control

    ERIC Educational Resources Information Center

    Caplan, Leslie J.; Schooler, Carmi

    2007-01-01

    We examine the relations among socioeconomic status, control beliefs, and two coping styles (problem-focused vs. emotion-focused) in the context of financial stress. Findings indicate that low socioeconomic status (SES) is linked to greater use of emotion-focused financial coping and lesser use of problem-focused financial coping. The effects of…

  6. Socioeconomic development in Sichuan.

    PubMed

    Zhang, G

    1997-10-01

    This article discusses the socioeconomic development in Sichuan province in south-central China. The gross domestic product of Sichuan province was 298.5 billion yuan in 1996, which is the 8th highest level in the country. Sichuan accounts for 30% of the total economic output in West China. Grain output accounts for 7.3%, oil bearing seed output accounts for 6.4%, and meat output accounts for 12% of the national total. This province accounts for 5.6% of the national gross output value of agriculture, forestry, animal husbandry, and fishery, which is the 6th largest proportion in the nation. In 1996, total industrial output was valued at 234.6 billion yuan. Sichuan also has considerable commerce, trade, culture, and education. In 1996, Sichuan had 42 universities and colleges with enrollments of 131,00 students and 6615 postgraduates. The province had 215 secondary vocational schools with an enrollment of 21,700 trainees. 4506 secondary schools had an enrollment of 2.766 million students. 48,911 primary schools had an enrollment of 7.8 million students. In 1996, Sichuan had 13,963 health units with 189,000 beds and 246,000 health and medical workers, of whom 123,000 were doctors and 60,000 were nurses. The population aged over 60 years numbered 8.55 million persons, or 10.2% of provincial total population. It is expected that the number of elderly will reach 9.32 million by the year 2000. There are about 3861 homes and institutions of welfare for the aged, 40 apartment complexes for the elderly, over 700 hospitals and clinics serving the elderly, and 430 schools or universities for the aged.

  7. The Rieske Fe/S protein of the cytochrome b6/f complex in chloroplasts: missing link in the evolution of protein transport pathways in chloroplasts?

    PubMed

    Molik, S; Karnauchov, I; Weidlich, C; Herrmann, R G; Klösgen, R B

    2001-11-16

    The Rieske Fe/S protein, a nuclear-encoded subunit of the cytochrome b(6)/f complex in chloroplasts, is retarded in the stromal space after import into the chloroplast and only slowly translocated further into the thylakoid membrane system. As shown by the sensitivity to nigericin and to specific competitor proteins, thylakoid transport takes place by the DeltapH-dependent TAT pathway. The Rieske protein is an untypical TAT substrate, however. It is only the second integral membrane protein shown to utilize this pathway, and it is the first authentic substrate without a cleavable signal peptide. Transport is instead mediated by the NH(2)-terminal membrane anchor, which lacks, however, the twin-arginine motif indicative of DeltapH/TAT-dependent transport signals. Furthermore, transport is affected by sodium azide as well as by competitor proteins for the Sec pathway in chloroplasts, demonstrating for the first time some cross-talk of the two pathways. This might take place in the stroma where the Rieske protein accumulates after import in several complexes of high molecular mass, among which the cpn60 complex is the most prominent. These untypical features suggest that the Rieske protein represents an intermediate or early state in the evolution of the thylakoidal protein transport pathways. PMID:11526115

  8. Exposure to socioeconomic adversity in early life and risk of depression at 18 years: The mediating role of locus of control

    PubMed Central

    Culpin, Iryna; Stapinski, Lexine; Miles, Ömür Budanur; Araya, Ricardo; Joinson, Carol

    2015-01-01

    Background Previous studies have linked exposure to early socioeconomic adversity to depression, but the mechanisms of this association are not well understood. Locus of control (LoC), an individual's control-related beliefs, has been implicated as a possible mechanism, however, longitudinal evidence to support this is lacking. Methods The study sample comprised 8803 participants from a UK cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Indicators of early socioeconomic adversity were collected from the antenatal period to 5 years and modelled as a latent factor. Depression was assessed using the Clinical Interview Schedule-Revised (CIS-R) at 18 years. LoC was assessed with the Nowicki–Strickland Internal–External (CNSIE) scale at 16 years. Results Using structural equation modelling, we found that 34% of the total estimated association between early socioeconomic adversity and depression at 18 years was explained by external LoC at 16 years. There was weak evidence of a direct pathway from early socioeconomic adversity to depression after accounting for the indirect effect via external locus of control. Socioeconomic adversity was associated with more external LoC, which, in turn, was associated with depression. Limitations Attrition may have led to an underestimation of the direct and indirect effect sizes in the complete case analysis. Conclusions Results suggest that external LoC in adolescence is one of the factors mediating the link between early adversity and depression at 18 years. Cognitive interventions that seek to modify maladaptive control beliefs in adolescence may be effective in reducing risk of depression following early life adversity. PMID:26047304

  9. Socioeconomic Status, IQ, and Delinquency.

    ERIC Educational Resources Information Center

    Moffitt, Terrie E.; And Others

    1981-01-01

    Results from two Danish prospective longitudinal studies are presented to support the view that IQ bears a causal relationship to delinquency that is independent of the effects of socioeconomic status (SES). (CL)

  10. Radical SAM, A Novel Protein Superfamily Linking Unresolved Steps in Familiar Biosynthetic Pathways with Radical Mechanisms: Functional Characterization Using New Analysis and Information Visualization Methods

    SciTech Connect

    Sofia, Heidi J.; Chen, Guang; Hetzler, Elizabeth G.; Reyes Spindola, Jorge F.; Miller, Nancy E.

    2001-03-01

    A large protein superfamily with over 500 members has been discovered and analyzed using powerful new bioinformatics and information visualization methods. Evidence exists that these proteins generate a 5?-deoxyadenosyl radical by reductive cleavage of S-adenosylmethionine (SAM) through an unusual Fe-S center. Radical SAM superfamily proteins function in DNA precursor, vitamin, cofactor, antibiotic, and herbicide biosynthesis in a collection of basic and familiar pathways. One of the members is interferon-inducible and is considered a candidate drug target for osteoporosis. The identification of this superfamily suggests that radical-based catalysis is important in a number of previously well-studied but unresolved biochemical pathways.

  11. Pathways and trajectories linking housing instability and poor health among low-income women experiencing intimate partner violence (IPV): Toward a conceptual framework.

    PubMed

    Daoud, Nihaya; Matheson, Flora I; Pedersen, Cheryl; Hamilton-Wright, Sarah; Minh, Anita; Zhang, Janice; O'Campo, Patricia

    2016-01-01

    We used grounded theory to understand pathways and trajectories to housing instability (HI) and poor health among low-income women with experiences of intimate partner violence (IPV). We conducted in-depth interviews during 2010-11 with forty-one women (ages 18-45 years) living in Ontario, Canada. All women reported depressive symptoms in combination with other health problems. In addition to the direct pathway of IPV to poor health, thematic analysis revealed an indirect multi-tiered pathway with complex trajectories among IPV, HI, and poor health. These trajectories included material HI (homelessness, high mobility, evictions, problems paying rent, hiding, and landlord discrimination), psychological HI (feeling unsafe, low self-esteem, and poor control), and social trajectories (financial problems, loss of employment, income, or social networks, and leaving school). These trajectories elevated stress and decreased self-care (unhealthy behaviors, substance abuse, and reduced medical compliance) and exacerbated poor health already compromised by IPV. Depending on her specific context, each woman experienced these pathways and trajectories differently. Moreover, the women's experiences differed across three time periods: before, immediately after, and long after leaving an abusive relationship. Finally, we found that for these women, achieving stable housing was crucial for stabilizing their health. PMID:26358378

  12. A Cross-Case Analysis of Career Pathway Programs That Link Low-Skilled Adults to Family-Sustaining Wage Careers. In Brief

    ERIC Educational Resources Information Center

    Bragg, Debra D.; Bremer, Christine D.; Castellano, Marisa; Kirby, Catherine; Mavis, Ann; Schaad, Donna; Sunderman, Judith

    2007-01-01

    Little is known about educational programs referred to as "career pathway programs" that attempt to integrate adult literacy, adult basic education (ABE), General Equivalency Diploma (GED) instruction, English language literacy (ELL), and pre-collegiate developmental education with postsecondary career and technical education (CTE) certificate and…

  13. Regulation of p53 and Rb Links the Alternative NF-κB Pathway to EZH2 Expression and Cell Senescence

    PubMed Central

    Iannetti, Alessio; Ledoux, Adeline C.; Tudhope, Susan J.; Sellier, Hélène; Zhao, Bo; Mowla, Sophia; Moore, Adam; Hummerich, Holger; Gewurz, Benjamin E.; Cockell, Simon J.; Jat, Parmjit S.; Willmore, Elaine; Perkins, Neil D.

    2014-01-01

    There are two major pathways leading to induction of NF-κB subunits. The classical (or canonical) pathway typically leads to the induction of RelA or c-Rel containing complexes, and involves the degradation of IκBα in a manner dependent on IκB kinase (IKK) β and the IKK regulatory subunit NEMO. The alternative (or non-canonical) pathway, involves the inducible processing of p100 to p52, leading to the induction of NF-κB2(p52)/RelB containing complexes, and is dependent on IKKα and NF-κB inducing kinase (NIK). Here we demonstrate that in primary human fibroblasts, the alternative NF-κB pathway subunits NF-κB2 and RelB have multiple, but distinct, effects on the expression of key regulators of the cell cycle, reactive oxygen species (ROS) generation and protein stability. Specifically, following siRNA knockdown, quantitative PCR, western blot analyses and chromatin immunoprecipitation (ChIP) show that NF-κB2 regulates the expression of CDK4 and CDK6, while RelB, through the regulation of genes such as PSMA5 and ANAPC1, regulates the stability of p21WAF1 and the tumour suppressor p53. These combine to regulate the activity of the retinoblastoma protein, Rb, leading to induction of polycomb protein EZH2 expression. Moreover, our ChIP analysis demonstrates that EZH2 is also a direct NF-κB target gene. Microarray analysis revealed that in fibroblasts, EZH2 antagonizes a subset of p53 target genes previously associated with the senescent cell phenotype, including DEK and RacGAP1. We show that this pathway provides the major route of crosstalk between the alternative NF-κB pathway and p53, a consequence of which is to suppress cell senescence. Importantly, we find that activation of NF-κB also induces EZH2 expression in CD40L stimulated cells from Chronic Lymphocytic Leukemia patients. We therefore propose that this pathway provides a mechanism through which microenvironment induced NF-κB can inhibit tumor suppressor function and promote tumorigenesis. PMID

  14. Enhancing NAD+ Salvage Pathway Reverts the Toxicity of Primary Astrocytes Expressing Amyotrophic Lateral Sclerosis-linked Mutant Superoxide Dismutase 1 (SOD1).

    PubMed

    Harlan, Benjamin A; Pehar, Mariana; Sharma, Deep R; Beeson, Gyda; Beeson, Craig C; Vargas, Marcelo R

    2016-05-13

    Nicotinamide adenine dinucleotide (NAD(+)) participates in redox reactions and NAD(+)-dependent signaling pathways. Although the redox reactions are critical for efficient mitochondrial metabolism, they are not accompanied by any net consumption of the nucleotide. On the contrary, NAD(+)-dependent signaling processes lead to its degradation. Three distinct families of enzymes consume NAD(+) as substrate: poly(ADP-ribose) polymerases, ADP-ribosyl cyclases (CD38 and CD157), and sirtuins (SIRT1-7). Because all of the above enzymes generate nicotinamide as a byproduct, mammalian cells have evolved an NAD(+) salvage pathway capable of resynthesizing NAD(+) from nicotinamide. Overexpression of the rate-limiting enzyme in this pathway, nicotinamide phosphoribosyltransferase, increases total and mitochondrial NAD(+) levels in astrocytes. Moreover, targeting nicotinamide phosphoribosyltransferase to the mitochondria also enhances NAD(+) salvage pathway in astrocytes. Supplementation with the NAD(+) precursors nicotinamide mononucleotide and nicotinamide riboside also increases NAD(+) levels in astrocytes. Amyotrophic lateral sclerosis (ALS) is caused by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. Superoxide dismutase 1 (SOD1) mutations account for up to 20% of familial ALS and 1-2% of apparently sporadic ALS cases. Primary astrocytes isolated from mutant human superoxide dismutase 1-overexpressing mice as well as human post-mortem ALS spinal cord-derived astrocytes induce motor neuron death in co-culture. Increasing total and mitochondrial NAD(+) content in ALS astrocytes increases oxidative stress resistance and reverts their toxicity toward co-cultured motor neurons. Taken together, our results suggest that enhancing the NAD(+) salvage pathway in astrocytes could be a potential therapeutic target to prevent astrocyte-mediated motor neuron death in ALS. PMID:27002158

  15. Targeting of the signal transducer Smo links microRNA-326 to the oncogenic Hedgehog pathway in CD34+ CML stem/progenitor cells.

    PubMed

    Babashah, Sadegh; Sadeghizadeh, Majid; Hajifathali, Abbas; Tavirani, Mostafa Rezaei; Zomorod, Mina Soufi; Ghadiani, Mojtaba; Soleimani, Masoud

    2013-08-01

    Aberrant expression and function of microRNAs (miRNAs) in leukemia have added a new layer of complexity to the understanding of development and progression of the disease state. However, their targeting of specific signaling pathways responsible for the maintenance and survival properties of leukemic stem cell (LSC) still remains to be further clarified. Hedgehog (Hh) signaling, a highly conserved developmental pathway, has been proven as a functional pathway for LSCs, and loss of this pathway impairs the development of BCR-ABL-induced chronic myeloid leukemia (CML) and depletes CML stem cells. Here, we revealed that upregulation of the Hh smoothened (Smo) signal transducer was associated with reduced expression of miR-326 in the CD34(+) cells from a group of patients with CML at diagnosis. Additionally, overexpression of miR-326 led to downregulation of Smo, resulted in decreased cell proliferation and elevated rate of apoptosis in CML CD34(+) cells. Interestingly, restoration of Smo expression levels reversed the effect of miR-326 and rescued K562 cells from the antiproliferative effects of this miRNA. Thus, Smo appears to be an essential target of miR-326 during the pathogenesis of CML. These findings lead us to suggest that downregulation of miR-326 may be a possible mechanism for unrestricted activation of Smo signal transducer of the oncogenic Hh pathway in CML; therefore, the restoration of miR-326 expression could be of benefit in eradicating CD34(+) CML stem/progenitor cells that represent a potential source of relapse in patients suffering CML.

  16. Pathway modulators and inhibitors.

    PubMed

    Smith, John A

    2009-07-01

    Inhibitors of specific cellular pathways are useful for investigating the roles of proteins of unknown function, and for selectively inhibiting a protein in complex pathways to uncover its relationships to other proteins in this and other interacting pathways. This appendix provides links to Web sites that describe cellular processes and pathways along with the various classes of inhibitors, numerous references, downloadable diagrams, and technical tips.

  17. Socio-economic benefits from protected areas in southeastern Australia.

    PubMed

    Heagney, E C; Kovac, M; Fountain, J; Conner, N

    2015-12-01

    International case studies of protected area performance increasingly report that conservation and socio-economic outcomes are interdependent. Effective conservation requires support and cooperation from local governments and communities, which in turn requires that protected areas contribute to the economic well-being of the communities in which they are sited. Despite increasing recognition of their importance, robust studies that document the socio-economic impacts of protected areas are rare, especially in the developed world context. We proposed 3 potential pathways through which protected areas might benefit local communities in the developed world: the improved local housing value, local business stimulus, and increased local funding pathways. We examined these pathways by undertaking a statistical longitudinal analysis of 110 regional and rural communities covering an area of approximately 600,000 km(2) in southeastern Australia. We compared trends in 10 socio-economic indicators describing employment, income, housing, business development and local government revenue from 2000 to 2010. New protected areas acquisitions led to an increased number of new dwelling approvals and associated developer contributions, increased local business numbers, and increased local government revenue from user-pays services and grants. Longer-term effects of established protected areas included increased local council revenue from a variety of sources. Our findings provide support for each of our 3 proposed benefit pathways and contribute new insights into the cycling of benefits from protected areas through the economy over time. The business and legislative models in our study are typical of those operating in many other developed countries; thus, the benefit pathways reported in our study are likely to be generalizable. By identifying and communicating socio-economic benefits from terrestrial protected areas in a developed world context, our findings represent an important

  18. Socio-economic benefits from protected areas in southeastern Australia.

    PubMed

    Heagney, E C; Kovac, M; Fountain, J; Conner, N

    2015-12-01

    International case studies of protected area performance increasingly report that conservation and socio-economic outcomes are interdependent. Effective conservation requires support and cooperation from local governments and communities, which in turn requires that protected areas contribute to the economic well-being of the communities in which they are sited. Despite increasing recognition of their importance, robust studies that document the socio-economic impacts of protected areas are rare, especially in the developed world context. We proposed 3 potential pathways through which protected areas might benefit local communities in the developed world: the improved local housing value, local business stimulus, and increased local funding pathways. We examined these pathways by undertaking a statistical longitudinal analysis of 110 regional and rural communities covering an area of approximately 600,000 km(2) in southeastern Australia. We compared trends in 10 socio-economic indicators describing employment, income, housing, business development and local government revenue from 2000 to 2010. New protected areas acquisitions led to an increased number of new dwelling approvals and associated developer contributions, increased local business numbers, and increased local government revenue from user-pays services and grants. Longer-term effects of established protected areas included increased local council revenue from a variety of sources. Our findings provide support for each of our 3 proposed benefit pathways and contribute new insights into the cycling of benefits from protected areas through the economy over time. The business and legislative models in our study are typical of those operating in many other developed countries; thus, the benefit pathways reported in our study are likely to be generalizable. By identifying and communicating socio-economic benefits from terrestrial protected areas in a developed world context, our findings represent an important

  19. Merlin/NF2 loss-driven tumorigenesis linked to CRL4(DCAF1)-mediated inhibition of the hippo pathway kinases Lats1 and 2 in the nucleus.

    PubMed

    Li, Wei; Cooper, Jonathan; Zhou, Lu; Yang, Chenyi; Erdjument-Bromage, Hediye; Zagzag, David; Snuderl, Matija; Ladanyi, Marc; Hanemann, C Oliver; Zhou, Pengbo; Karajannis, Matthias A; Giancotti, Filippo G

    2014-07-14

    It is currently unclear whether Merlin/NF2 suppresses tumorigenesis by activating upstream components of the Hippo pathway at the plasma membrane or by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. We found that derepressed CRL4(DCAF1) promotes YAP- and TEAD-dependent transcription by ubiquitylating and, thereby, inhibiting Lats1 and 2 in the nucleus. Genetic epistasis experiments and analysis of tumor-derived missense mutations indicate that this signaling connection sustains the oncogenicity of Merlin-deficient tumor cells. Analysis of clinical samples confirms that this pathway operates in NF2-mutant tumors. We conclude that derepressed CRL4(DCAF1) promotes activation of YAP by inhibiting Lats1 and 2 in the nucleus. PMID:25026211

  20. Atf1-Pcr1-M26 Complex Links Stress-activated MAPK and cAMP-dependent Protein Kinase Pathways via Chromatin Remodeling of cgs2+*

    PubMed Central

    Davidson, Mari K.; Shandilya, Harish K.; Hirota, Kouji; Ohta, Kunihiro; Wahls, Wayne P.

    2011-01-01

    Although co-ordinate interaction between different signal transduction pathways is essential for developmental decisions, interpathway connections are often obscured and difficult to identify due to cross-talk. Here signals from the fission yeast stress-activated MAPK Spc1 are shown to regulate Cgs2, a negative regulator of the cAMP-dependent protein kinase (protein kinase A) pathway. Pathway integration is achieved via Spc1-dependent binding of Atf1-Pcr1 heterodimer to an M26 DNA site in the cgs2+ promoter, which remodels chromatin to regulate expression of cgs2+ and targets downstream of protein kinase A. This direct interpathway connection co-ordinates signals of nitrogen and carbon source depletion to affect a G0 cell-cycle checkpoint and sexual differentiation. The Atf1-Pcr1-M26 complex-dependent chromatin remodeling provides a molecular mechanism whereby Atf1-Pcr1 heterodimer can function differentially as either a transcriptional activator, or as a transcriptional repressor, or as an inducer of meiotic recombination. We also show that the Atf1-Pcr1-M26 complex functions as both an inducer and repressor of chromatin remodeling, which provides a way for various chromatin remodeling-dependent effector functions to be regulated. PMID:15448137

  1. Atf1-Pcr1-M26 complex links stress-activated MAPK and cAMP-dependent protein kinase pathways via chromatin remodeling of cgs2+.

    PubMed

    Davidson, Mari K; Shandilya, Harish K; Hirota, Kouji; Ohta, Kunihiro; Wahls, Wayne P

    2004-12-01

    Although co-ordinate interaction between different signal transduction pathways is essential for developmental decisions, interpathway connections are often obscured and difficult to identify due to cross-talk. Here signals from the fission yeast stress-activated MAPK Spc1 are shown to regulate Cgs2, a negative regulator of the cAMP-dependent protein kinase (protein kinase A) pathway. Pathway integration is achieved via Spc1-dependent binding of Atf1-Pcr1 heterodimer to an M26 DNA site in the cgs2+ promoter, which remodels chromatin to regulate expression of cgs2+ and targets downstream of protein kinase A. This direct interpathway connection co-ordinates signals of nitrogen and carbon source depletion to affect a G0 cell-cycle checkpoint and sexual differentiation. The Atf1-Pcr1-M26 complex-dependent chromatin remodeling provides a molecular mechanism whereby Atf1-Pcr1 heterodimer can function differentially as either a transcriptional activator, or as a transcriptional repressor, or as an inducer of meiotic recombination. We also show that the Atf1-Pcr1-M26 complex functions as both an inducer and repressor of chromatin remodeling, which provides a way for various chromatin remodeling-dependent effector functions to be regulated. PMID:15448137

  2. Atf1-Pcr1-M26 complex links stress-activated MAPK and cAMP-dependent protein kinase pathways via chromatin remodeling of cgs2+.

    PubMed

    Davidson, Mari K; Shandilya, Harish K; Hirota, Kouji; Ohta, Kunihiro; Wahls, Wayne P

    2004-12-01

    Although co-ordinate interaction between different signal transduction pathways is essential for developmental decisions, interpathway connections are often obscured and difficult to identify due to cross-talk. Here signals from the fission yeast stress-activated MAPK Spc1 are shown to regulate Cgs2, a negative regulator of the cAMP-dependent protein kinase (protein kinase A) pathway. Pathway integration is achieved via Spc1-dependent binding of Atf1-Pcr1 heterodimer to an M26 DNA site in the cgs2+ promoter, which remodels chromatin to regulate expression of cgs2+ and targets downstream of protein kinase A. This direct interpathway connection co-ordinates signals of nitrogen and carbon source depletion to affect a G0 cell-cycle checkpoint and sexual differentiation. The Atf1-Pcr1-M26 complex-dependent chromatin remodeling provides a molecular mechanism whereby Atf1-Pcr1 heterodimer can function differentially as either a transcriptional activator, or as a transcriptional repressor, or as an inducer of meiotic recombination. We also show that the Atf1-Pcr1-M26 complex functions as both an inducer and repressor of chromatin remodeling, which provides a way for various chromatin remodeling-dependent effector functions to be regulated.

  3. A Pil1–Sle1–Syj1–Tax4 functional pathway links eisosomes with PI(4,5)P2 regulation

    PubMed Central

    Kabeche, Ruth; Roguev, Assen; Krogan, Nevan J.; Moseley, James B.

    2014-01-01

    ABSTRACT Stable compartments of the plasma membrane promote a wide range of cellular functions. In yeast cells, cytosolic structures called eisosomes generate prominent cortical invaginations of unknown function. Through a series of genetic screens in fission yeast, we found that the eisosome proteins Pil1 and Sle1 function with the synaptojanin-like lipid phosphatase Syj1 and its ligand Tax4. This genetic pathway connects eisosome function with the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] in cells. Defects in PI(4,5)P2 regulation led to eisosome defects, and we found that the core eisosome protein Pil1 can bind to and tubulate liposomes containing PI(4,5)P2. Mutations in components of the Pil1–Sle1–Syj1–Tax4 pathway suppress the growth and morphology defects of TORC2 mutants, indicating that eisosome-dependent regulation of PI(4,5)P2 feeds into signal transduction pathways. We propose that the geometry of membrane invaginations generates spatial and temporal signals for lipid-mediated signaling events in cells. PMID:24434583

  4. Effect of ethnicity and socioeconomic variation to the gut microbiota composition among pre-adolescent in Malaysia.

    PubMed

    Chong, Chun Wie; Ahmad, Arine Fadzlun; Lim, Yvonne Ai Lian; Teh, Cindy Shuan Ju; Yap, Ivan Kok Seng; Lee, Soo Ching; Chin, Yuee Teng; Loke, P'ng; Chua, Kek Heng

    2015-01-01

    Gut microbiota plays an important role in mammalian host metabolism and physiological functions. The functions are particularly important in young children where rapid mental and physical developments are taking place. Nevertheless, little is known about the gut microbiome and the factors that contribute to microbial variation in the gut of South East Asian children. Here, we compared the gut bacterial richness and composition of pre-adolescence in Northern Malaysia. Our subjects covered three distinct ethnic groups with relatively narrow range of socioeconomic discrepancy. These included the Malays (n = 24), Chinese (n = 17) and the Orang Asli (indigenous) (n = 20). Our results suggested a strong ethnicity and socioeconomic-linked bacterial diversity. Highest bacterial diversity was detected from the economically deprived indigenous children while the lowest diversity was recorded from the relatively wealthy Chinese children. In addition, predicted functional metagenome profiling suggested an over-representation of pathways pertinent to bacterial colonisation and chemotaxis in the former while the latter exhibited enriched gene pathways related to sugar metabolism. PMID:26290472

  5. Effect of ethnicity and socioeconomic variation to the gut microbiota composition among pre-adolescent in Malaysia

    PubMed Central

    Chong, Chun Wie; Ahmad, Arine Fadzlun; Lim, Yvonne Ai Lian; Teh, Cindy Shuan Ju; Yap, Ivan Kok Seng; Lee, Soo Ching; Chin, Yuee Teng; Loke, P’ng; Chua, Kek Heng

    2015-01-01

    Gut microbiota plays an important role in mammalian host metabolism and physiological functions. The functions are particularly important in young children where rapid mental and physical developments are taking place. Nevertheless, little is known about the gut microbiome and the factors that contribute to microbial variation in the gut of South East Asian children. Here, we compared the gut bacterial richness and composition of pre-adolescence in Northern Malaysia. Our subjects covered three distinct ethnic groups with relatively narrow range of socioeconomic discrepancy. These included the Malays (n = 24), Chinese (n = 17) and the Orang Asli (indigenous) (n = 20). Our results suggested a strong ethnicity and socioeconomic-linked bacterial diversity. Highest bacterial diversity was detected from the economically deprived indigenous children while the lowest diversity was recorded from the relatively wealthy Chinese children. In addition, predicted functional metagenome profiling suggested an over-representation of pathways pertinent to bacterial colonisation and chemotaxis in the former while the latter exhibited enriched gene pathways related to sugar metabolism. PMID:26290472

  6. Acetylcholinesterase (AChE) is an important link in the apoptotic pathway induced by hyperglycemia in Y79 retinoblastoma cell line

    PubMed Central

    Masha'our, R. Shehadeh; Heinrich, R.; Garzozi, H. J.; Perlman, I.

    2012-01-01

    Acetylcholinesterase (AChE) expression was found to be induced in the mammalian CNS, including the retina, by different types of stress leading to cellular apoptosis. Here, we tested possible involvement of AChE in hyperglycemia-induced apoptosis in a retinal cell line. Y79 retinoblastoma cells were incubated in starvation media (1% FBS and 1 mg/ml glucose) for 16–24 h, and then exposed to hyperglycemic environment by raising extracellular glucose concentrations to a final level of 3.5 mg/ml or 6 mg/ml. Similar levels of mannitol were used as control for hyperosmolarity. Cells were harvested at different time intervals for analysis of apoptosis and AChE protein expression. Apoptosis was detected by the cleavage of Poly ADP-ribose polymerase (PARP) using western blot, and by Terminal deoxynucleotidyl-transferase-mediated dUTP nick-end-labeling (TUNEL) assay. AChE protein expression and activity was detected by western blot and by the Karnovsky and Roots method, respectively. MissionTM shRNA for AChE was used to inhibit AChE protein expression. Treating Y79 cells with 3.5 mg/ml of glucose, but not with 3.5 mg/ml mannitol, induced apoptosis which was confirmed by TUNEL assay and by cleavage of PARP. A part of the signaling pathway accompanying the apoptotic process involved up-regulation of the AChE-R variant and an N-extended AChE variant as verified at the mRNA and protein level. Inhibition of AChE protein expression by shRNA protected Y79 cell from entering the apoptotic pathway. Our data suggest that expression of an N-extended AChE variant, most probably an R isoform, is involved in the apoptotic pathway caused by hyperglycemia in Y79 cells. PMID:22685426

  7. Reduced NODAL signaling strength via mutation of several pathway members including FOXH1 is linked to human heart defects and holoprosencephaly.

    PubMed

    Roessler, Erich; Ouspenskaia, Maia V; Karkera, Jayaprakash D; Vélez, Jorge I; Kantipong, Amy; Lacbawan, Felicitas; Bowers, Peter; Belmont, John W; Towbin, Jeffrey A; Goldmuntz, Elizabeth; Feldman, Benjamin; Muenke, Maximilian

    2008-07-01

    Abnormalities of embryonic patterning are hypothesized to underlie many common congenital malformations in humans including congenital heart defects (CHDs), left-right disturbances (L-R) or laterality, and holoprosencephaly (HPE). Studies in model organisms suggest that Nodal-like factors provide instructions for key aspects of body axis and germ layer patterning; however, the complex genetics of pathogenic gene variant(s) in humans are poorly understood. Here we report our studies of FOXH1, CFC1, and SMAD2 and summarize our mutational analysis of three additional components in the human NODAL-signaling pathway: NODAL, GDF1, and TDGF1. We identify functionally abnormal gene products throughout the pathway that are clearly associated with CHD, laterality, and HPE. Abnormal gene products are most commonly detected in patients within a narrow spectrum of isolated conotruncal heart defects (minimum 5%-10% of subjects), and far less commonly in isolated laterality or HPE patients (approximately 1% for each). The difference in the mutation incidence between these groups is highly significant. We show that apparent gene dosage discrepancies between humans and model organisms can be reconciled by considering a broader combination of sequence variants. Our studies confirm that (1) the genetic vulnerabilities inferred from model organisms with defects in Nodal signaling are indeed analogous to humans; (2) the molecular analysis of an entire signaling pathway is more complete and robust than that of individual genes and presages future studies by whole-genome analysis; and (3) a functional genomics approach is essential to fully appreciate the complex genetic interactions necessary to produce these effects in humans.

  8. Acetylcholinesterase (AChE) is an important link in the apoptotic pathway induced by hyperglycemia in Y79 retinoblastoma cell line.

    PubMed

    Masha'our, R Shehadeh; Heinrich, R; Garzozi, H J; Perlman, I

    2012-01-01

    Acetylcholinesterase (AChE) expression was found to be induced in the mammalian CNS, including the retina, by different types of stress leading to cellular apoptosis. Here, we tested possible involvement of AChE in hyperglycemia-induced apoptosis in a retinal cell line. Y79 retinoblastoma cells were incubated in starvation media (1% FBS and 1 mg/ml glucose) for 16-24 h, and then exposed to hyperglycemic environment by raising extracellular glucose concentrations to a final level of 3.5 mg/ml or 6 mg/ml. Similar levels of mannitol were used as control for hyperosmolarity. Cells were harvested at different time intervals for analysis of apoptosis and AChE protein expression. Apoptosis was detected by the cleavage of Poly ADP-ribose polymerase (PARP) using western blot, and by Terminal deoxynucleotidyl-transferase-mediated dUTP nick-end-labeling (TUNEL) assay. AChE protein expression and activity was detected by western blot and by the Karnovsky and Roots method, respectively. Mission(TM) shRNA for AChE was used to inhibit AChE protein expression. Treating Y79 cells with 3.5 mg/ml of glucose, but not with 3.5 mg/ml mannitol, induced apoptosis which was confirmed by TUNEL assay and by cleavage of PARP. A part of the signaling pathway accompanying the apoptotic process involved up-regulation of the AChE-R variant and an N-extended AChE variant as verified at the mRNA and protein level. Inhibition of AChE protein expression by shRNA protected Y79 cell from entering the apoptotic pathway. Our data suggest that expression of an N-extended AChE variant, most probably an R isoform, is involved in the apoptotic pathway caused by hyperglycemia in Y79 cells. PMID:22685426

  9. Socio-economic characteristics of patients with glioblastoma multiforme.

    PubMed

    Muquit, Samiul; Parks, Ruth; Basu, Surajit

    2015-11-01

    The incidence of glioblastoma multiforme (GBM) varies across the world and also within subpopulations within each nation. Many cancers show correlation with socioeconomic status and we hypothesised that incidence of GBM also does the same. We performed a retrospective analysis of all patients treated with brain tumours at a single hospital over a 6-year period. For these patients we examined markers of socioeconomic status and reviewed their histopathological diagnosis. A total of 2859 patients had surgery between April 2006 and April 2012. Of these 880 had histological diagnosis of GBM. Records for all patients were reviewed. Based on postcodes, socioeconomic data was obtained at ward level from government sources. Markers were: average weekly household income, percentage unemployed, population density, indices of deprivation and percentage of households with no car. Data was analysed for trends between incidence per ward and socio-economic markers. Increasing incidence of GBM was associated with increasing wage (p = 0.044), less unemployment (p = 0.0002), Indices of Multiple Deprivation (p = 0.05), lower population density (p = 0.0015) and greater ownership of cars (p = 0.0005). There are unique socioeconomic characteristics for patients with GBM. Although a link to aetiology cannot be established from this limited epidemiological study, these results identify issues that these patients are more likely to face. These should be taken into account when planning support services and patient care following surgery. PMID:26334316

  10. Integrative Analyses of miRNA-mRNA Interactions Reveal let-7b, miR-128 and MAPK Pathway Involvement in Muscle Mass Loss in Sex-Linked Dwarf Chickens

    PubMed Central

    Luo, Wen; Lin, Shumao; Li, Guihuan; Nie, Qinghua; Zhang, Xiquan

    2016-01-01

    The sex-linked dwarf (SLD) chicken is an ideal model system for understanding growth hormone (GH)-action and growth hormone receptor (GHR) function because of its recessive mutation in the GHR gene. Skeletal muscle mass is reduced in the SLD chicken with a smaller muscle fiber diameter. Our previous study has presented the mRNA and miRNA expression profiles of the SLD chicken and normal chicken between embryo day 14 and seven weeks of age. However, the molecular mechanism of GHR-deficient induced muscle mass loss is still unclear, and the key molecules and pathways underlying the GHR-deficient induced muscle mass loss also remain to be illustrated. Here, by functional network analysis of the differentially expressed miRNAs and mRNAs between the SLD and normal chickens, we revealed that let-7b, miR-128 and the MAPK pathway might play key roles in the GHR-deficient induced muscle mass loss, and that the reduced cell division and growth are potential cellular processes during the SLD chicken skeletal muscle development. Additionally, we also found some genes and miRNAs involved in chicken skeletal muscle development, through the MAPK, PI3K-Akt, Wnt and Insulin signaling pathways. This study provides new insights into the molecular mechanism underlying muscle mass loss in the SLD chickens, and some regulatory networks that are crucial for chicken skeletal muscle development. PMID:26927061

  11. The p-eIF2α/ATF4 pathway links endoplasmic reticulum stress to autophagy following the production of reactive oxygen species in mouse spermatocyte-derived cells exposed to dibutyl phthalate.

    PubMed

    Zhang, Guowei; Ling, Xi; Liu, Kaijun; Wang, Zhi; Zou, Peng; Gao, Jianfang; Cao, Jia; Ao, Lin

    2016-07-01

    Dibutyl phthalate (DBP) is a widely used plasticizer that has been shown to induce germ cell apoptosis-related testicular atrophy and cause reproductive toxicity. Our previous results indicated that endoplasmic reticulum (ER) stress-activated autophagy served as a self-defense mechanism against DBP-induced germ cell apoptosis. However, the specific pathways that link ER stress and autophagy remain unclear. Here, we showed that exposure to DBP enhanced autophagic flux in mouse spermatocyte-derived GC-2 cells and that the eukaryotic translation initiation factor 2/activating transcription factor 4 pathway mediated ER stress-related autophagy independent of the mTOR and Beclin-1 pathways. Moreover, we demonstrated that DBP treatment led to the generation of reactive oxygen species (ROS) and that the inhibition of ROS by melatonin abrogated both ER stress and autophagy. The results indicated that excessive ROS production might be involved in DBP-induced ER stress and autophagy in GC-2 cells. Thus, ROS may serve as upstream mediators of ER stress and autophagy in DBP-treated GC-2 cells. PMID:27002192

  12. Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC

    PubMed Central

    Zhou, Weihua; Liu, Feng; Zhang, Bin; Zhu, Min; Yang, Qin; Zeng, Yayue; Sun, Yang; Sun, Shuming; Wang, Yanpeng; Zhang, Yibin; Weng, Haibo; Chen, Lixiang; Ye, Mao; An, Xiuli; Liu, Jing

    2016-01-01

    Protein 4.1N is a member of protein 4.1 family and has been recognized as a potential tumor suppressor in solid tumors. Here, we aimed to investigate the role and mechanisms of 4.1N in non-small cell lung cancer (NSCLC). We confirmed that the expression level of 4.1N was inversely correlated with the metastatic properties of NSCLC cell lines and histological grade of clinical NSCLC tissues. Specific knockdown of 4.1N promoted tumor cell proliferation, migration and adhesion in vitro, and tumor growth and metastasis in mouse xenograft models. Furthermore, we identified PP1 as a novel 4.1N-interacting molecule, and the FERM domain of 4.1N mediated the interaction between 4.1N and PP1. Further, ectopic expression of 4.1N could inactivate JNK-c-Jun signaling pathway through enhancing PP1 activity and interaction between PP1 and p-JNK. Correspondingly, expression of potential downstream metastasis targets (ezrin and MMP9) and cell cycle targets (p53, p21 and p19) of JNK-c-Jun pathway were also regulated by 4.1N. Our data suggest that down-regulation of 4.1N expression is a critical step for NSCLC development and that repression of JNK-c-Jun signaling through PP1 is one of the key anti-tumor mechanisms of 4.1N. PMID:26575790

  13. RNA-Seq Links the Transcription Factors AINTEGUMENTA and AINTEGUMENTA-LIKE6 to Cell Wall Remodeling and Plant Defense Pathways1[OPEN

    PubMed Central

    Bequette, Carlton J.; Fu, Zheng Qing; Loraine, Ann E.

    2016-01-01

    AINTEGUMENTA (ANT) and AINTEGUMENTA-LIKE6 (AIL6) are two related transcription factors in Arabidopsis (Arabidopsis thaliana) that have partially overlapping roles in several aspects of flower development, including floral organ initiation, identity specification, growth, and patterning. To better understand the biological processes regulated by these two transcription factors, we performed RNA sequencing (RNA-Seq) on ant ail6 double mutants. We identified thousands of genes that are differentially expressed in the double mutant compared with the wild type. Analyses of these genes suggest that ANT and AIL6 regulate floral organ initiation and growth through modifications to the cell wall polysaccharide pectin. We found reduced levels of demethylesterified homogalacturonan and altered patterns of auxin accumulation in early stages of ant ail6 flower development. The RNA-Seq experiment also revealed cross-regulation of AIL gene expression at the transcriptional level. The presence of a number of overrepresented Gene Ontology terms related to plant defense in the set of genes differentially expressed in ant ail6 suggest that ANT and AIL6 also regulate plant defense pathways. Furthermore, we found that ant ail6 plants have elevated levels of two defense hormones: salicylic acid and jasmonic acid, and show increased resistance to the bacterial pathogen Pseudomonas syringae. These results suggest that ANT and AIL6 regulate biological pathways that are critical for both development and defense. PMID:27208279

  14. Nox Complex signal and MAPK cascade pathway are cross-linked and essential for pathogenicity and conidiation of mycoparasite Coniothyrium minitans

    PubMed Central

    Wei, Wei; Zhu, Wenjun; Cheng, Jiasen; Xie, Jiatao; Jiang, Daohong; Li, Guoqing; Chen, Weidong; Fu, Yanping

    2016-01-01

    The NADPH oxidase complex of a sclerotial mycoparasite Coniothyrium minitans, an important biocontrol agent against crop diseases caused by Sclerotinia sclerotiorum, was identified and its functions involved in conidiation and mycoparasitism were studied. Gene knock-out and complementary experiments indicated that CmNox1, but not CmNox2, is necessary for conidiation and parasitism, and its expression could be significantly induced by its host fungus. CmNox1 is regulated by CmRac1-CmNoxR and interacts with CmSlt2, a homolog of Saccharomyces cerevisiae Slt2 encoding cell wall integrity-related MAP kinase. In ΔCmNox1, CmSlt2-GFP fusion protein lost the ability to localize to the cell nucleus accurately. The defect of conidiation in ΔCmRac1 could be partially restored by over-expressing CmSlt2, indicating that CmSlt2 was a downstream regulatory factor of CmNox1 and was involved in conidiation and parasitism. The expressions of mycoparasitism-related genes CmPks1, Cmg1 and CH1 were suppressed in the knock-out mutants of the genes in CmNox1-CmSlt2 signal pathway when cultivated either on PDA. Therefore, our study infers that CmRac1-CmNoxR regulates CmNox1-CmSlt2 pathway in regulating conidiation and pathogenicity of C. minitans. PMID:27066837

  15. Genetic profile of GNAQ-mutated blue melanocytic neoplasms reveals mutations in genes linked to genomic instability and the PI3K pathway

    PubMed Central

    Pérez-Alea, Mileidys; Vivancos, Ana; Caratú, Ginevra; Matito, Judit; Ferrer, Berta; Hernandez-Losa, Javier; Cortés, Javier; Muñoz, Eva; Garcia-Patos, Vicente; Recio, Juan A.

    2016-01-01

    Melanomas arising in association with a common or cellular blue nevus (MABN) comprise a relatively rare and heterogeneous group of lethal melanomas. Although GNAQ is known to be frequently mutated in common blue nevus, cellular blue nevus (CBN) and MABN and these malignant lesions present gross chromosome alterations harboring BAP1 mutations, little is known about other mutations that contribute to the development and progression of these neoplasms. Thus, the genetic profile of these tumors is important to increase the number of intervention and treatment modalities. Here, we characterized and genetically profiled two different sections of a rare MABN and two CBNs from three different patients. All of the samples harbored a GNAQ mutation, exhibited RAS pathway activation, and harbored additional mutations in genes associated with genomic instability and epigenetic regulation (KMT2C, FANCD2, ATR, ATRX, NBN, ERCC2, SETD2, and WHSC1). In addition, all neoplasms harbored mutations that directly or indirectly affected either the regulation or activation of the PI3K pathway (PIK3CA, NF1, INPP5B and GSK3B). Our results not only help understand the genetic complexity of these blue melanocytic lesions but provide a rationale to use the combination of PI3K/MTOR and MEK1/2 inhibitors against these types of tumors. PMID:27057633

  16. Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders.

    PubMed

    Moreno-Ramos, Oscar A; Olivares, Ana María; Haider, Neena B; de Autismo, Liga Colombiana; Lattig, María Claudia

    2015-01-01

    Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian-South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T>C (p.I505T)) and FOXN1 (RefSeq NM_003593: c.146C>T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in ~E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; ~P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding.

  17. Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders

    PubMed Central

    Moreno-Ramos, Oscar A.; Olivares, Ana María; Haider, Neena B.; de Autismo, Liga Colombiana; Lattig, María Claudia

    2015-01-01

    Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian—South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T>C (p.I505T)) and FOXN1 (RefSeq NM_003593: c.146C>T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in ~E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; ~P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding. PMID:26352270

  18. Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders.

    PubMed

    Moreno-Ramos, Oscar A; Olivares, Ana María; Haider, Neena B; de Autismo, Liga Colombiana; Lattig, María Claudia

    2015-01-01

    Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian-South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T>C (p.I505T)) and FOXN1 (RefSeq NM_003593: c.146C>T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in ~E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; ~P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding. PMID:26352270

  19. Linking regional sources and pathways for submarine groundwater discharge at a reef by electrical resistivity tomography, 222Rn, and salinity measurements

    NASA Astrophysics Data System (ADS)

    Cardenas, M. Bayani; Zamora, Peter B.; Siringan, Fernando P.; Lapus, Mark R.; Rodolfo, Raymond S.; Jacinto, Gil S.; San Diego-McGlone, Maria Lourdes; Villanoy, Cesar L.; Cabrera, Olivia; Senal, Maria Isabel

    2010-08-01

    Submarine groundwater discharge (SGD) is an important component of the hydrologic cycle connecting terrestrial to marine environments. SGD in fringing reefs and its consequences on biogeochemistry and ecology remain mostly unexplored. The 222Rn activity and salinity of seawater indicate a substantial groundwater contribution throughout most of the 20 km2 studied tropical reef in Pangasinan, Philippines. Over 30 km of electrical resistivity profiles with a penetration depth of 12.5 m shows widespread zones within the reef that are much more resistive than porous reef rocks or sediment saturated with typical seawater. Some discrete resistive areas are located close to where seawater has 222Rn peaks and where geologic lineaments are likely located suggesting that these are preferential pathways for fresher groundwater discharging to the reef. SGD at the site could be a major ecological factor connecting the reef to the subsurface environment which in turn may lead to connections to land.

  20. Socioeconomic Outcomes from Adult Education.

    ERIC Educational Resources Information Center

    Gooderham, Paul N.

    1991-01-01

    The degree to which age and gender influence completion of higher secondary education (HSE) and employment status was measured with a sample of 350 Norwegian adults. Application of a Status Attainment model revealed that post-HSE educational attainment is an important determinant of socioeconomic status for both men and women. (SK)

  1. Tourette syndrome and socioeconomic status.

    PubMed

    Aldred, Mark; Cavanna, Andrea E

    2015-09-01

    Tourette syndrome (TS) is a neurodevelopmental disorder characterised by multiple motor and vocal tics. Co-morbid behavioural problems are common and include obsessive-compulsive disorder, attention-deficit and hyperactivity disorder, depression and anxiety. Both tics and behavioural symptoms tend to have a chronic course and can affect patients' health-related quality of life; however, little is known about the relationship between TS, social status and occupation. We conducted an exploratory study on a clinical sample of 137 adult patients with TS to investigate the association between the core features of TS (both tic severity ratings and behavioural co-morbidities) and socioeconomic class. Both clinician- and patient-reported tic severity ratings were significantly higher amongst unemployed patients, compared to patients in the highest socioeconomic class (P = 0.004 and P < 0.001, respectively). There were no significant differences in socioeconomic class distribution between patients with TS and co-morbid behavioural problems ('TS plus', n = 88) and patients with uncomplicated TS ('pure TS', n = 49) (P = 0.205). Our findings suggest that higher tic severity can have far-reaching consequences on patients' life, as it appears to be selectively associated with unemployment and lower socioeconomic status. These observations prompt further research into the complex relationship between TS and social status.

  2. Socioeconomic Determinants of Academic Achievement

    ERIC Educational Resources Information Center

    Tomul, Ekber; Savasci, Havva Sebile

    2012-01-01

    This study aims to investigate the relationship between academic achievement and the socioeconomic characteristics of elementary school 7th grade students in Burdur. The population of the study are 7th grade students who had education at elementary schools in Burdur in the 2007-2008 academic year. Two staged sampling was chosen as suitable for the…

  3. Families' Social Backgrounds Matter: Socio-Economic Factors, Home Learning and Young Children's Language, Literacy and Social Outcomes

    ERIC Educational Resources Information Center

    Hartas, Dimitra

    2011-01-01

    Parental support with children's learning is considered to be one pathway through which socio-economic factors influence child competencies. Utilising a national longitudinal sample from the Millennium Cohort Study, this study examined the relationship between home learning and parents' socio-economic status and their impact on young children's…

  4. Life Stressors as Mediators of the Relation between Socioeconomic Position and Mental Health Problems in Early Adolescence: The TRAILS Study

    ERIC Educational Resources Information Center

    Amone-P'Olak, Kennedy; Ormel, Johan; Huisman, Martijn; Verhulst, Frank C.; Oldehinkel, Albertine J.; Burger, Huibert

    2009-01-01

    Objective: Life stressors and family socioeconomic position have often been associated with mental health status. The aim of the present study is to contribute to the understanding of the pathways from low socioeconomic position and life stressors to mental problems. Method: In a cross-sectional analysis using data from a longitudinal study of…

  5. Plant Aquaporin AtPIP1;4 Links Apoplastic H2O2 Induction to Disease Immunity Pathways1[OPEN

    PubMed Central

    Tian, Shan; Wang, Xiaobing; Li, Ping; Wang, Hao; Ji, Hongtao; Xie, Junyi; Qiu, Qinglei

    2016-01-01

    Hydrogen peroxide (H2O2) is a stable component of reactive oxygen species, and its production in plants represents the successful recognition of pathogen infection and pathogen-associated molecular patterns (PAMPs). This production of H2O2 is typically apoplastic but is subsequently associated with intracellular immunity pathways that regulate disease resistance, such as systemic acquired resistance and PAMP-triggered immunity. Here, we elucidate that an Arabidopsis (Arabidopsis thaliana) aquaporin (i.e. the plasma membrane intrinsic protein AtPIP1;4) acts to close the cytological distance between H2O2 production and functional performance. Expression of the AtPIP1;4 gene in plant leaves is inducible by a bacterial pathogen, and the expression accompanies H2O2 accumulation in the cytoplasm. Under de novo expression conditions, AtPIP1;4 is able to mediate the translocation of externally applied H2O2 into the cytoplasm of yeast (Saccharomyces cerevisiae) cells. In plant cells treated with H2O2, AtPIP1;4 functions as an effective facilitator of H2O2 transport across plasma membranes and mediates the translocation of externally applied H2O2 from the apoplast to the cytoplasm. The H2O2-transport role of AtPIP1;4 is essentially required for the cytoplasmic import of apoplastic H2O2 induced by the bacterial pathogen and two typical PAMPs in the absence of induced production of intracellular H2O2. As a consequence, cytoplasmic H2O2 quantities increase substantially while systemic acquired resistance and PAMP-triggered immunity are activated to repress the bacterial pathogenicity. By contrast, loss-of-function mutation at the AtPIP1;4 gene locus not only nullifies the cytoplasmic import of pathogen- and PAMP-induced apoplastic H2O2 but also cancels the subsequent immune responses, suggesting a pivotal role of AtPIP1;4 in apocytoplastic signal transduction in immunity pathways. PMID:26945050

  6. Inference of Longevity-Related Genes from a Robust Coexpression Network of Seed Maturation Identifies Regulators Linking Seed Storability to Biotic Defense-Related Pathways.

    PubMed

    Righetti, Karima; Vu, Joseph Ly; Pelletier, Sandra; Vu, Benoit Ly; Glaab, Enrico; Lalanne, David; Pasha, Asher; Patel, Rohan V; Provart, Nicholas J; Verdier, Jerome; Leprince, Olivier; Buitink, Julia

    2015-10-01

    Seed longevity, the maintenance of viability during storage, is a crucial factor for preservation of genetic resources and ensuring proper seedling establishment and high crop yield. We used a systems biology approach to identify key genes regulating the acquisition of longevity during seed maturation of Medicago truncatula. Using 104 transcriptomes from seed developmental time courses obtained in five growth environments, we generated a robust, stable coexpression network (MatNet), thereby capturing the conserved backbone of maturation. Using a trait-based gene significance measure, a coexpression module related to the acquisition of longevity was inferred from MatNet. Comparative analysis of the maturation processes in M. truncatula and Arabidopsis thaliana seeds and mining Arabidopsis interaction databases revealed conserved connectivity for 87% of longevity module nodes between both species. Arabidopsis mutant screening for longevity and maturation phenotypes demonstrated high predictive power of the longevity cross-species network. Overrepresentation analysis of the network nodes indicated biological functions related to defense, light, and auxin. Characterization of defense-related wrky3 and nf-x1-like1 (nfxl1) transcription factor mutants demonstrated that these genes regulate some of the network nodes and exhibit impaired acquisition of longevity during maturation. These data suggest that seed longevity evolved by co-opting existing genetic pathways regulating the activation of defense against pathogens. PMID:26410298

  7. The disease-linked Glu-26-Lys mutant version of Coronin 1A exhibits pleiotropic and pathway-specific signaling defects

    PubMed Central

    Ojeda, Virginia; Robles-Valero, Javier; Barreira, María; Bustelo, Xosé R.

    2015-01-01

    Coronin 1A (Coro1A) is involved in cytoskeletal and signaling events, including the regulation of Rac1 GTPase– and myosin II–dependent pathways. Mutations that generate truncated or unstable Coro1A proteins cause immunodeficiencies in both humans and rodents. However, in the case of the peripheral T-cell–deficient (Ptcd) mouse strain, the immunodeficiency is caused by a Glu-26-Lys mutation that targets a surface-exposed residue unlikely to affect the intramolecular architecture and stability of the protein. Here we report that this mutation induces pleiotropic effects in Coro1A protein, including the exacerbation of Coro1A-dependent actin-binding and -bundling activities; the formation of large meshworks of Coro1AE26K-decorated filaments endowed with unusual organizational, functional, and staining properties; and the elimination of Coro1A functions associated with both Rac1 and myosin II signaling. By contrast, it does not affect the ability of Coro1A to stimulate the nuclear factor of activated T-cells (NF-AT). Coro1AE26K is not a dominant-negative mutant, indicating that its pathological effects are derived from the inability to rescue the complete loss of the wild-type counterpart in cells. These results indicate that Coro1AE26K behaves as either a recessive gain-of-function or loss-of-function mutant protein, depending on signaling context and presence of the wild-type counterpart in cells. PMID:26108624

  8. Inference of Longevity-Related Genes from a Robust Coexpression Network of Seed Maturation Identifies Regulators Linking Seed Storability to Biotic Defense-Related Pathways

    PubMed Central

    Righetti, Karima; Vu, Joseph Ly; Pelletier, Sandra; Vu, Benoit Ly; Glaab, Enrico; Lalanne, David; Pasha, Asher; Patel, Rohan V.; Provart, Nicholas J.; Verdier, Jerome; Leprince, Olivier

    2015-01-01

    Seed longevity, the maintenance of viability during storage, is a crucial factor for preservation of genetic resources and ensuring proper seedling establishment and high crop yield. We used a systems biology approach to identify key genes regulating the acquisition of longevity during seed maturation of Medicago truncatula. Using 104 transcriptomes from seed developmental time courses obtained in five growth environments, we generated a robust, stable coexpression network (MatNet), thereby capturing the conserved backbone of maturation. Using a trait-based gene significance measure, a coexpression module related to the acquisition of longevity was inferred from MatNet. Comparative analysis of the maturation processes in M. truncatula and Arabidopsis thaliana seeds and mining Arabidopsis interaction databases revealed conserved connectivity for 87% of longevity module nodes between both species. Arabidopsis mutant screening for longevity and maturation phenotypes demonstrated high predictive power of the longevity cross-species network. Overrepresentation analysis of the network nodes indicated biological functions related to defense, light, and auxin. Characterization of defense-related wrky3 and nf-x1-like1 (nfxl1) transcription factor mutants demonstrated that these genes regulate some of the network nodes and exhibit impaired acquisition of longevity during maturation. These data suggest that seed longevity evolved by co-opting existing genetic pathways regulating the activation of defense against pathogens. PMID:26410298

  9. Epigenetic Signatures May Explain the Relationship Between Socioeconomic Position and Risk of Mental Illness: Preliminary Findings from an Urban Community Based Sample

    PubMed Central

    Uddin, Monica; Galea, Sandro; Chang, Shun Chiao; Koenen, Karestan C.; Goldmann, Emily; Wildman, Derek E.; Aiello, Allison E.

    2013-01-01

    Low socioeconomic position (SEP) has previously been linked to a number of negative health indicators, including poor mental health. The biologic mechanisms linking SEP and mental health remain poorly understood. Recent work suggests that social exposures influence DNA methylation in a manner salient to mental health. We conducted a pilot investigation to assess whether SEP, measured as educational attainment, modifies the association between genomic methylation profiles and traumatic stress in a trauma-exposed sample. Results show that methylation × SEP interactions occur preferentially in genes pertaining to nervous system function, suggesting a plausible biologic pathway by which SEP may enhance sensitivity to stress, and, in turn, risk of post-traumatic stress disorder. PMID:23701537

  10. Measures of Socioeconomic Status: Alternatives and Recommendations.

    ERIC Educational Resources Information Center

    Mueller, Charles, W.; Parcel, Toby L.

    1981-01-01

    Criticizes impressionistic or outdated measures of socioeconomic status, recommends the Duncan Socioeconomic Index and the Siegel Prestige Scale, and describes a strategy for measuring household or family SES when household composition and characteristics vary. (Author/DB)

  11. The link in Linking

    PubMed Central

    Caldwell, Jane C; Chiale, Pablo A; Gonzalez, Mario D; Baranchuk, Adrian

    2013-01-01

    We present 2 cases of the slow-fast form of AVNRT with initially narrow QRS complexes followed by sudden unexpected transition to persistently wide QRS complexes due to aberrant intraventricular conduction. Introduction of a properly timed extrastimulus in one case and critical oscillations in cycle length due to short-long coupling in the second case set the stage for the initial bundle branch block. However, persistence of the aberrancy pattern once the initial event abated was maintained by the "linking" phenomenon. Delayed, retrograde concealed activation from the contralateral bundle branch perpetuated the initial bundle branch block. PMID:23840106

  12. A Disulfide Bond-forming Machine Is Linked to the Sortase-mediated Pilus Assembly Pathway in the Gram-positive Bacterium Actinomyces oris.

    PubMed

    Reardon-Robinson, Melissa E; Osipiuk, Jerzy; Chang, Chungyu; Wu, Chenggang; Jooya, Neda; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

    2015-08-28

    Export of cell surface pilins in Gram-positive bacteria likely occurs by the translocation of unfolded precursor polypeptides; however, how the unfolded pilins gain their native conformation is presently unknown. Here, we present physiological studies to demonstrate that the FimA pilin of Actinomyces oris contains two disulfide bonds. Alanine substitution of cysteine residues forming the C-terminal disulfide bridge abrogates pilus assembly, in turn eliminating biofilm formation and polymicrobial interaction. Transposon mutagenesis of A. oris yielded a mutant defective in adherence to Streptococcus oralis, and revealed the essential role of a vitamin K epoxide reductase (VKOR) gene in pilus assembly. Targeted deletion of vkor results in the same defects, which are rescued by ectopic expression of VKOR, but not a mutant containing an alanine substitution in its conserved CXXC motif. Depletion of mdbA, which encodes a membrane-bound thiol-disulfide oxidoreductase, abrogates pilus assembly and alters cell morphology. Remarkably, overexpression of MdbA or a counterpart from Corynebacterium diphtheriae, rescues the Δvkor mutant. By alkylation assays, we demonstrate that VKOR is required for MdbA reoxidation. Furthermore, crystallographic studies reveal that A. oris MdbA harbors a thioredoxin-like fold with the conserved CXXC active site. Consistently, each MdbA enzyme catalyzes proper disulfide bond formation within FimA in vitro that requires the catalytic CXXC motif. Because the majority of signal peptide-containing proteins encoded by A. oris possess multiple Cys residues, we propose that MdbA and VKOR constitute a major folding machine for the secretome of this organism. This oxidative protein folding pathway may be a common feature in Actinobacteria.

  13. Serotonergic neural links from the dorsal raphe nucleus modulate defensive behaviours organised by the dorsomedial hypothalamus and the elaboration of fear-induced antinociception via locus coeruleus pathways.

    PubMed

    Biagioni, Audrey Francisco; de Freitas, Renato Leonardo; da Silva, Juliana Almeida; de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Alves, Vani Maria; Coimbra, Norberto Cysne

    2013-04-01

    Decrease of γ-aminobutyric acid (GABA)-mediated neurotransmission in the dorsomedial hypothalamus (DMH) evokes instinctive fear-like responses. The aim of the present study was to investigate the involvement of the serotonin (5-HT)- and norepinephrine-mediated pathways of the endogenous pain inhibitory system, including the dorsal raphe nucleus (DRN) and the locus coeruleus (LC), in the defensive responses and antinociceptive processes triggered by the blockade of GABAergic receptors in the DMH. The intra-hypothalamic microinjection of the GABA(A) receptor antagonist bicuculline (40 ng/200 nL) elicited elaborate defensive behaviours interspersed with exploratory responses. This escape behaviour was followed by significantly increased pain thresholds, a phenomenon known as fear-induced antinociception. Furthermore, at 5 and 14 days after DRN serotonin-containing neurons were damaged using the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), the frequency and duration of alertness and escape behaviour evoked by the GABA(A) receptor blockade in the DMH decreased, as well as fear-induced antinociception. Pre-treatment with the non-selective 5-HT receptor antagonist methysergide, the 5-HT(2A/2C) receptor antagonist ketanserin and the 5-HT(2A) receptor selective antagonist R-96544 in the LC also decreased fear-induced antinociception, without significant changes in the expression of defensive behaviours. These data suggest that the serotonergic neurons of the DRN are directly involved in the organisation of defensive responses as well as in the elaboration of the innate fear-induced antinociception. However, serotonin-mediated inputs from the NDR to the LC modulate only fear-induced antinociception and not the defensive behaviours evoked by GABA(A) receptor blockade in the DMH. PMID:23201351

  14. Serotonergic neural links from the dorsal raphe nucleus modulate defensive behaviours organised by the dorsomedial hypothalamus and the elaboration of fear-induced antinociception via locus coeruleus pathways.

    PubMed

    Biagioni, Audrey Francisco; de Freitas, Renato Leonardo; da Silva, Juliana Almeida; de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Alves, Vani Maria; Coimbra, Norberto Cysne

    2013-04-01

    Decrease of γ-aminobutyric acid (GABA)-mediated neurotransmission in the dorsomedial hypothalamus (DMH) evokes instinctive fear-like responses. The aim of the present study was to investigate the involvement of the serotonin (5-HT)- and norepinephrine-mediated pathways of the endogenous pain inhibitory system, including the dorsal raphe nucleus (DRN) and the locus coeruleus (LC), in the defensive responses and antinociceptive processes triggered by the blockade of GABAergic receptors in the DMH. The intra-hypothalamic microinjection of the GABA(A) receptor antagonist bicuculline (40 ng/200 nL) elicited elaborate defensive behaviours interspersed with exploratory responses. This escape behaviour was followed by significantly increased pain thresholds, a phenomenon known as fear-induced antinociception. Furthermore, at 5 and 14 days after DRN serotonin-containing neurons were damaged using the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), the frequency and duration of alertness and escape behaviour evoked by the GABA(A) receptor blockade in the DMH decreased, as well as fear-induced antinociception. Pre-treatment with the non-selective 5-HT receptor antagonist methysergide, the 5-HT(2A/2C) receptor antagonist ketanserin and the 5-HT(2A) receptor selective antagonist R-96544 in the LC also decreased fear-induced antinociception, without significant changes in the expression of defensive behaviours. These data suggest that the serotonergic neurons of the DRN are directly involved in the organisation of defensive responses as well as in the elaboration of the innate fear-induced antinociception. However, serotonin-mediated inputs from the NDR to the LC modulate only fear-induced antinociception and not the defensive behaviours evoked by GABA(A) receptor blockade in the DMH.

  15. Racial discrimination & health: pathways & evidence.

    PubMed

    Ahmed, Ameena T; Mohammed, Selina A; Williams, David R

    2007-10-01

    This review provides an overview of the existing empirical research of the multiple ways by which discrimination can affect health. Institutional mechanisms of discrimination such as restricting marginalized groups to live in undesirable residential areas can have deleterious health consequences by limiting socio-economic status (SES) and creating health-damaging conditions in residential environments. Discrimination can also adversely affect health through restricting access to desirable services such as medical care and creating elevated exposure to traditional stressors such as unemployment and financial strain. Central to racism is an ideology of inferiority that can adversely affect non-dominant groups because some members of marginalized populations will accept as true the dominant society's ideology of their group's inferiority. Limited empirical research indicates that internalized racism is inversely related to health. In addition, the existence of these negative stereotypes can lead dominant group members to consciously and unconsciously discriminate against the stigmatized. An overview of the growing body of research examining the ways in which psychosocial stress generated by subjective experiences of discrimination can affect health is also provided. We review the evidence from the United States and other societies that suggest that the subjective experience of discrimination can adversely affect health and health enhancing behaviours. Advancing our understanding of the relationship between discrimination and health requires improved assessment of the phenomenon of discrimination and increased attention to identifying the psychosocial and biological pathways that may link exposure to discrimination to health status.

  16. Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy.

    PubMed

    Muona, Mikko; Ishimura, Ryosuke; Laari, Anni; Ichimura, Yoshinobu; Linnankivi, Tarja; Keski-Filppula, Riikka; Herva, Riitta; Rantala, Heikki; Paetau, Anders; Pöyhönen, Minna; Obata, Miki; Uemura, Takefumi; Karhu, Thomas; Bizen, Norihisa; Takebayashi, Hirohide; McKee, Shane; Parker, Michael J; Akawi, Nadia; McRae, Jeremy; Hurles, Matthew E; Kuismin, Outi; Kurki, Mitja I; Anttonen, Anna-Kaisa; Tanaka, Keiji; Palotie, Aarno; Waguri, Satoshi; Lehesjoki, Anna-Elina; Komatsu, Masaaki

    2016-09-01

    The ubiquitin fold modifier 1 (UFM1) cascade is a recently identified evolutionarily conserved ubiquitin-like modification system whose function and link to human disease have remained largely uncharacterized. By using exome sequencing in Finnish individuals with severe epileptic syndromes, we identified pathogenic compound heterozygous variants in UBA5, encoding an activating enzyme for UFM1, in two unrelated families. Two additional individuals with biallelic UBA5 variants were identified from the UK-based Deciphering Developmental Disorders study and one from the Northern Finland Intellectual Disability cohort. The affected individuals (n = 9) presented in early infancy with severe irritability, followed by dystonia and stagnation of development. Furthermore, the majority of individuals display postnatal microcephaly and epilepsy and develop spasticity. The affected individuals were compound heterozygous for a missense substitution, c.1111G>A (p.Ala371Thr; allele frequency of 0.28% in Europeans), and a nonsense variant or c.164G>A that encodes an amino acid substitution p.Arg55His, but also affects splicing by facilitating exon 2 skipping, thus also being in effect a loss-of-function allele. Using an in vitro thioester formation assay and cellular analyses, we show that the p.Ala371Thr variant is hypomorphic with attenuated ability to transfer the activated UFM1 to UFC1. Finally, we show that the CNS-specific knockout of Ufm1 in mice causes neonatal death accompanied by microcephaly and apoptosis in specific neurons, further suggesting that the UFM1 system is essential for CNS development and function. Taken together, our data imply that the combination of a hypomorphic p.Ala371Thr variant in trans with a loss-of-function allele in UBA5 underlies a severe infantile-onset encephalopathy. PMID:27545674

  17. Socioeconomic Drought in a Changing Climate: Modeling and Management

    NASA Astrophysics Data System (ADS)

    AghaKouchak, Amir; Mehran, Ali; Mazdiyasni, Omid

    2016-04-01

    Drought is typically defined based on meteorological, hydrological and land surface conditions. However, in many parts of the world, anthropogenic changes and water management practices have significantly altered local water availability. Socioeconomic drought refers to conditions whereby the available water supply cannot satisfy the human and environmental water needs. Surface water reservoirs provide resilience against local climate variability (e.g., droughts), and play a major role in regional water management. This presentation focuses on a framework for describing socioeconomic drought based on both water supply and demand information. We present a multivariate approach as a measure of socioeconomic drought, termed Multivariate Standardized Reliability and Resilience Index (MSRRI; Mehran et al., 2015). This model links the information on inflow and surface reservoir storage to water demand. MSRRI integrates a "top-down" and a "bottom-up" approach for describing socioeconomic drought. The "top-down" component describes processes that cannot be simply controlled or altered by local decision-makers and managers (e.g., precipitation, climate variability, climate change), whereas the "bottom-up" component focuses on the local resilience, and societal capacity to respond to droughts. The two components (termed, Inflow-Demand Reliability (IDR) indicator and Water Storage Resilience (WSR) indicator) are integrated using a nonparametric multivariate approach. We use this framework to assess the socioeconomic drought during the Australian Millennium Drought (1998-2010) and the 2011-2014 California Droughts. MSRRI provides additional information on socioeconomic drought onset, development and termination based on local resilience and human demand that cannot be obtained from the commonly used drought indicators. We show that MSRRI can be used for water management scenario analysis (e.g., local water availability based on different human water demands scenarios). Finally

  18. Describing socioeconomic gradients in children’s diets – does the socioeconomic indicator used matter?

    PubMed Central

    2014-01-01

    Background Children of low socioeconomic position (SEP) generally have poorer diets than children of high SEP. However there is no consensus on which SEP variable is most indicative of SEP differences in children’s diets. This study investigated associations between diet and various SEP indicators among children aged 9–13 years. Method Families (n = 625) were recruited from 27 Adelaide primary schools in 2010. Children completed semi-quantitative food frequency questionnaires providing intake scores for fruit, vegetables, non-core foods, sweetened drinks, and healthy and unhealthy eating behaviours. Parents reported demographic information by telephone interview. Differences in dietary intake scores were compared across parental education, income, occupation, employment status and home postcode. Results Across most SEP indicators, lower SEP was associated with poorer dietary outcomes, including higher intake of non-core foods and sweetened drinks, and more unhealthy behaviours; and lower intake of fruit and vegetables, and fewer healthy behaviours. The number and type of significant SEP-diet associations differed across SEP indicators and dietary outcomes. Mother’s education appeared most frequently as a predictor of children’s dietary intake, and postcode was the least frequent predictor of children’s dietary intake. Conclusion Socioeconomic gradients in children’s dietary intake varied according to the SEP indicator used, suggesting indicator-specific pathways of influence on children’s dietary intake. Researchers should consider multiple indicators when defining SEP in relation to children’s eating. PMID:24674231

  19. Evidence That the Product of the Human X-Linked Cgd Gene, Gp91-phox, Is a Voltage-Gated H+ Pathway

    PubMed Central

    Henderson, Lydia M.; Meech, Robert W.

    1999-01-01

    Expression of gp91-phox in Chinese hamster ovary (CHO91) cells is correlated with the presence of a voltage-gated H+ conductance. As one component of NADPH oxidase in neutrophils, gp91-phox is responsible for catalyzing the production of superoxide (O2·2). Suspensions of CHO91 cells exhibit arachidonate-activatable H+ fluxes (Henderson, L.M., G. Banting, and J.B. Chappell. 1995. J. Biol. Chem. 270:5909–5916) and we now characterize the electrical properties of the pathway. Voltage-gated currents were recorded from CHO91 cells using the whole-cell configuration of the patch-clamp technique under conditions designed to exclude a contribution from ions other than H+. As in other voltage-gated proton currents (Byerly, L., R. Meech, and W. Moody. 1984. J. Physiol. 351:199–216; DeCoursey, T.E., and V.V. Cherny. 1993. Biophys. J. 65:1590–1598), a lowered external pH (pHo) shifted activation to more positive voltages and caused the tail current reversal potential to shift in the manner predicted by the Nernst equation. The outward currents were also reversibly inhibited by 200 μM zinc. Voltage-gated currents were not present immediately upon perforating the cell membrane, but showed a progressive increase over the first 10–20 min of the recording period. This time course was consistent with a gradual shift in activation to more negative potentials as the pipette solution, pH 6.5, equilibrated with the cell contents (reported by Lucifer yellow included in the patch pipette). Use of the pH-sensitive dye 2′7′ bis-(2-carboxyethyl)-5(and 6) carboxyfluorescein (BCECF) suggested that the final intracellular pH (pHi) was ∼6.9, as though pHi was largely determined by endogenous cellular regulation. Arachidonate (20 μM) increased the amplitude of the currents by shifting activation to more negative voltages and by increasing the maximally available conductance. Changes in external Cl− concentration had no effect on either the time scale or the appearance of the

  20. Preventable hospitalizations and socioeconomic status.

    PubMed

    Blustein, J; Hanson, K; Shea, S

    1998-01-01

    "Preventable" hospitalizations have been proposed as indicators of poor health plan performance. In this study of elderly Medicare beneficiaries, however, we found that preventable hospitalizations are also more common among elders of lower socioeconomic status (SES). The relationship persisted even when an up-to-date severity-of-illness adjustment system was used. To the extent that indicators of health plan "performance" reflect enrollees' characteristics, plans will be rewarded for marketing their services to wealthier, healthier, and better-educated patients. Further work is needed to clarify issues of accountability for preventable hospitalizations and other putative indices of health plan performance. PMID:9558796

  1. Socioeconomic and Psychosocial Gradients in Cardiovascular Pathogen Burden and Immune Response: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Aiello, Allison E.; Diez-Roux, Ana; Noone, Anne-Michelle; Ranjit, Nalini; Cushman, Mary; Tsai, Michael Y.; Szklo, Moyses

    2009-01-01

    Background The biologic mechanisms linking socioeconomic position and psychosocial factors to cardiovascular disease (CVD) are not well understood. Immune response to persistent pathogens may be one of these mechanisms. Methods We analyzed cross-sectional data from the Multi-Ethnic Study of Atherosclerosis (N=999) composed of adults age 45–84. Log-binomial regression and ordinal logistic regression models were used to examine associations of socioeconomic factors and psychosocial factors with pathogen burden and immune response among those infected. Pathogen burden was assessed based on seroprevalence of Helicobacter pylori, cytomegalovirus, herpes simplex virus-1, and Chlamydia pneumoniae and antibody levels were used to characterize high immune response to all four pathogens. Results Low education was a strong and significant independent predictor of higher pathogen burden after adjustment for covariates (adjusted odds ratio (OR) 95% confidence interval (CI) 1.37, 1.19–1.57). Among subjects seropositive for all four pathogens, low education and a higher level of chronic psychosocial stress showed a positive association with higher antibody response, although associations were no longer significant in models with all covariates included (OR = 1.64, 95%CI 0.82–3.31 for lowest vs. highest educational category and OR= 1.29, 95%CI 0.96–1.73 for a one level increase in chronic stress). Conclusion Pathogen burden and heightened immune response may represent a biological pathway by which low socioeconomic position and chronic stress are related to increased rates of cardiovascular disease. PMID:19150399

  2. Aspirin-triggered resolvin D1 inhibits TGF-β1-induced EMT through the inhibition of the mTOR pathway by reducing the expression of PKM2 and is closely linked to oxidative stress.

    PubMed

    Liu, Yu; Yuan, Xiaolong; Li, Wenhui; Cao, Qianqian; Shu, Yusheng

    2016-10-01

    Transforming growth factor-β1 (TGF-β1) is a potent stimulator of the epithelial-to-mesenchymal transition (EMT), which is a key event in the initiation of tumor cell metastasis. Aspirin-triggered resolvin D1 (AT-RvD1) is known to be involved in the resolution of inflammation; however, whether AT-RvD1 exerts effects on TGF-β1-induced EMT remains unclear. Thus, we first explored the effects of AT-RvD1 on the EMT of lung cancer cells. Treatment with TGF-β1 increased the level of reactive oxygen species (ROS) and reduced the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The expression of E-cadherin in A549 lung cancer cells was reduced, and the expression of vimentin was enhanced. AT-RvD1 enhanced the expression of E-cadherin in a concentration‑dependent manner and suppressed the expression of Nrf2 and vimentin. AT-RvD1 did not affect the proliferation of A549 lung cancer cells whereas it suppressed the TGF-β1‑induced migration and invasion of A549 cells. The expression of pyruvate kinase M2 (Pkm2), which is associated with TGF-β-induced factor homeobox 2 (TGIF2), was significantly increased during the TGF-β1-induced EMT of A549 lung cancer cells. The mTOR pathway is known to regulate the expression of various glycolytic enzymes including Pkm2. We examined the involvement of the mTOR pathway in the suppressive effects of AT-RvD1 on Pkm2 expression in A549 cells. The mTOR activator restored the expression of Pkm2 and partially downregulated the expression of E-cadherin. However, the mTOR activator had no clear effect on the TGF-β1-induced EMT. These results suggest that AT-RvD1 is closely linked to oxidative stress and partially inhibits TGF-β1-induced EMT through the inhibition of the mTOR pathway by reducing the expression of Pkm2.

  3. Are clinical criteria just proxies for socioeconomic status? A study of low birth weight in Jamaica.

    PubMed Central

    Peabody, J W; Gertler, P J

    1997-01-01

    OBJECTIVE: To determine if the clinical risk factors for low birth weight are independent of socioeconomic risk factors in a population based sample from a developing country. DESIGN: Survey data from patient reported socioeconomic measures and their most recent pregnancy history. SETTING: A national sample of randomly selected households in Jamaica. SUBJECTS: All women aged 14-50 in the household who had a pregnancy lasting seven months in the past five years (n = 952). MAIN OUTCOME MEASURE: Birth weight. RESULTS: Clinical risk factors for low birth weight, such as parity age, are independent of socioeconomic determinants, such as consumption and where a mother lives. Women who are nulliparous, 35 or older, poor, or living in certain areas are more likely to have lower birth weight children than those that do not have these characteristics (t statistics > 2.0). The addition of socioeconomic factors to the multiple regression does not alter the estimates for the clinical risk factors for low birth weight. Thus, the effect of being nulliparous can be offset by being in the highest consumption quintile and, conversely, the risk of being older will be compounded if women are poor. CONCLUSIONS: Both clinical and socioeconomic risk factors should be used to target women at risk. In terms of the quality of care, this study links clinical and socioeconomic risk factors to poor outcomes. Further studies are needed, however, to link the quality of care at various locations to these outcomes. Images PMID:9135795

  4. Central neuromechanisms underlying control of intragastric pressure through acupuncture at Zusanli (ST36) in rats: the upper cervical cord is the key link between the ascending and descending pathways

    PubMed Central

    Yong, Chun-yan; Chen, Shu; Chen, Heng; Chu, Xiao; Zhang, Chao; Tan, Cheng; Ye, Lan; Li, Jiang-shan

    2016-01-01

    Sensory inputs stimulated by Zusanli (ST36) acupuncture in the abdomen are known to converge in the upper cervical cord. However, it is unclear whether these inputs are subsequently conveyed to the hypothalamic paraventricular nucleus and what kind of afferent fibers are involved. We focused on the upper cervical cord, where afferent inputs converge, and detected c-fos expression in oxytocinergic neurons. We found that Zusanli acupuncture therapy effectively elevated intragastric pressure, but inhibited expression of c-fos in oxytocinergic neurons of the paraventricular nucleus in upper cervical cord injured rats. These Zusanli acupuncture effects remained even after complete dorsal cord transection. However, after complete transection of the spinal cord or dorsolateral funiculus, the effects were significantly attenuated and even disappeared. These findings suggest that the paraventricular nucleus is responsible for pooling and integrating signals from the Zusanli acupuncture and sensory information from the intragastric pressure variation, thereby contributing to the regulation of intragastric pressure. The upper cervical cord serves as the key link between ascending and descending pathways, which conveys afferent inputs to the paraventricular nucleus through the dorsolateral funiculus. PMID:27482227

  5. A syndecan-4 binding peptide derived from laminin 5 uses a novel PKCε pathway to induce cross-linked actin network (CLAN) formation in human trabecular meshwork (HTM) cells.

    PubMed

    Filla, Mark S; Clark, Ross; Peters, Donna M

    2014-10-01

    In this study, we examined the role(s) of syndecan-4 in regulating the formation of an actin geodesic dome structure called a cross-linked actin network (CLAN) in which syndecan-4 has previously been localized. CLANs have been described in several different cell types, but they have been most widely studied in human trabecular meshwork (HTM) cells where they may play a key role in controlling intraocular pressure by regulating aqueous humor outflow from the eye. In this study we show that a loss of cell surface synedcan-4 significantly reduces CLAN formation in HTM cells. Analysis of HTM cultures treated with or without dexamethasone shows that laminin 5 deposition within the extracellular matrix is increased by glucocorticoid treatment and that a laminin 5-derived, syndecan-4-binding peptide (PEP75), induces CLAN formation in TM cells. This PEP75-induced CLAN formation was inhibited by heparin and the broad spectrum PKC inhibitor Ro-31-7549. In contrast, the more specific PKCα inhibitor Gö 6976 had no effect, thus excluding PKCα as a downstream effector of syndecan-4 signaling. Analysis of PKC isozyme expression showed that HTM cells also expressed both PKCγ and PKCε. Cells treated with a PKCε agonist formed CLANs while a PKCα/γ agonist had no effect. These data suggest that syndecan-4 is essential for CLAN formation in HTM cells and that a novel PKCε-mediated signaling pathway can regulate formation of this unique actin structure. PMID:25128150

  6. A syndecan-4 binding peptide derived from laminin 5 uses a novel PKCε pathway to induce cross-linked actin network (CLAN) formation in human trabecular meshwork (HTM) cells

    PubMed Central

    Filla, Mark S.; Clark, Ross; Peters, Donna M.

    2014-01-01

    In this study, we examined the role(s) of syndecan-4 in regulating the formation of an actin geodesic dome structure called a cross-linked actin network (CLAN) in which syndecan-4 has previously been localized. CLANs have been described in several different cell types, but they have been most widely studied in human trabecular meshwork (HTM) cells where they may play a key role in controlling intraocular pressure by regulating aqueous humor outflow from the eye. In this study we show that a loss of cell surface synedcan-4 significantly reduces CLAN formation in HTM cells. Analysis of HTM cultures treated with or without dexamethasone shows that laminin 5 deposition within the extracellular matrix is increased by glucocorticoid treatment and that a laminin 5-derived, syndecan-4-binding peptide (PEP75), induces CLAN formation in TM cells. This PEP75-induced CLAN formation was inhibited by heparin and the broad spectrum PKC inhibitor Ro-31-7549. In contrast, the more specific PKCα inhibitor Go 6976 had no effect, thus excluding PKCα as a downstream effector of syndecan-4 signaling. Analysis of PKC isozyme expression showed that HTM cells also expressed both PKCγ and PKCε. Cells treated with a PKCε agonist formed CLANs while a PKCα/γ agonist had no effect. These data suggest that syndecan-4 is essential for CLAN formation in HTM cells and that a novel PKCε-mediated signaling pathway can regulate formation of this unique actin structure. PMID:25128150

  7. Socioeconomic Disparities in Health Behaviors

    PubMed Central

    Pampel, Fred C.; Krueger, Patrick M.; Denney, Justin T.

    2011-01-01

    The inverse relationships between socioeconomic status (SES) and unhealthy behaviors such as tobacco use, physical inactivity, and poor nutrition have been well demonstrated empirically but encompass diverse underlying causal mechanisms. These mechanisms have special theoretical importance because disparities in health behaviors, unlike disparities in many other components of health, involve something more than the ability to use income to purchase good health. Based on a review of broad literatures in sociology, economics, and public health, we classify explanations of higher smoking, lower exercise, poorer diet, and excess weight among low-SES persons into nine broad groups that specify related but conceptually distinct mechanisms. The lack of clear support for any one explanation suggests that the literature on SES disparities in health and health behaviors can do more to design studies that better test for the importance of the varied mechanisms. PMID:21909182

  8. Adolescent Precursors of Pathways from School to Work

    PubMed Central

    Vuolo, Mike; Mortimer, Jeylan T.; Staff, Jeremy

    2013-01-01

    Longitudinal data from the Youth Development Study is used to examine: (1) how young people establish work with self-identified career potential and how these patterns are linked to educational attainments; and (2) how adolescent achievement orientations, experiences in school and work, and sociodemographic background distinguish youth who establish themselves in careers and those who flounder during this transition. Multilevel latent class models reveal four school-to-work pathways from ages 18 to 31: two groups that attain careers through postsecondary education (via Bachelor’s or Associates-Vocational degrees) and two groups that do not (distinguished by attempting college). Multinomial logistic regression models demonstrate that academic orientations, socioeconomic background, and steady paid work during high school help adolescents avoid subsequent floundering during the school-to-work transition. PMID:24791132

  9. Socioeconomic gradients in mortality in the oldest old: a review.

    PubMed

    Guilley, Edith; Bopp, Matthias; Faeh, David; Paccaud, Fred

    2010-01-01

    This review aims at identifying gaps in knowledge on socioeconomic gradients in mortality in the oldest old. The authors review literature on oldest old population with a focus on unanswered questions: do socioeconomic status (SES) gradients in mortality persist after 80; does the magnitude of the gradient change as compared with younger populations; which socioeconomic/socio-demographic determinants should be used in this population with specific characteristics (e.g., with respect to sex ratio and household type)? Results are often inconsistent while conclusions drawn by selected studies are generally limited by the difficulty of disentangling the effects of age and cohort, and of generalizing results observed in preponderantly small, selected samples (which typically exclude institutionalized persons). Future research should explore the effects of socio-demographic indicators other than education and social class (e.g., marital status, loss of the partner) and adequately differentiate the social position of oldest old women. The authors recommend that research applies a life-course perspective combined with an interdisciplinary perspective to improve our understanding of the SES gradients in later life. Research is needed to elucidate which causal pathways depending on SES in younger age impact on mortality in higher ages up to oldest old.

  10. Community College Attendance and Socioeconomic Plans

    ERIC Educational Resources Information Center

    Park, Sueuk; Pascarella, Ernest T.

    2010-01-01

    Using data from the National Education Longitudinal Study, 1988 (NELS: 88), this paper documents differences in the socioeconomic plans of students in two-year and four-year colleges. We found attendance at a two-year college led to a modest but statistically significant disadvantage in socioeconomic plans. However, the impact of attending a…

  11. High School Socioeconomic Segregation and Student Attainment

    ERIC Educational Resources Information Center

    Palardy, Gregory J.

    2013-01-01

    Using data from the Education Longitudinal Study of 2002, this study examines the association between high school socioeconomic segregation and student attainment outcomes and the mechanisms that mediate those relationships. The results show that socioeconomic segregation has a strong association with high school graduation and college enrollment.…

  12. Increasing socioeconomic disparities in adolescent obesity.

    PubMed

    Frederick, Carl B; Snellman, Kaisa; Putnam, Robert D

    2014-01-28

    Recent reports suggest that the rapid growth in youth obesity seen in the 1980s and 1990s has plateaued. We examine changes in obesity among US adolescents aged 12-17 y by socioeconomic background using data from two nationally representative health surveys, the 1988-2010 National Health and Nutrition Examination Surveys and the 2003-2011 National Survey of Children's Health. Although the overall obesity prevalence stabilized, this trend masks a growing socioeconomic gradient: The prevalence of obesity among high-socioeconomic status adolescents has decreased in recent years, whereas the prevalence of obesity among their low-socioeconomic status peers has continued to increase. Additional analyses suggest that socioeconomic differences in the levels of physical activity, as well as differences in calorie intake, may have contributed to the growing obesity gradient.

  13. Socioeconomic assessment: issues, status, and plans

    SciTech Connect

    Boryczka, M.K.

    1983-01-01

    Numerous public meetings and hearings have been held in Texas, Mississippi, Louisiana and Utah on the issue of siting a nuclear waste repository in salt. Citizens in these potential site areas have raised many questions about how this facility will affect their quality of life. Questions about population and economic changes have been of particular concern. In developing a socioeconomic program, these issues and others have been an integral part of Battelle's socioeconomic studies. The three elements of Battelle's socioeconomic program are comprised of three elements: impact assessment, impact mitigation and community development, and impact monitoring. In addition, our approach to assessing socioeconomic impacts for the environmental assessment (EA) required by the Nuclear Waste Policy Act of 1982 are described. Since the EA analysis will address many of the issues raised in the site areas, these concerns will be elaborated on. Finally, various techniques for managing socioeconomic impacts will be presented. 6 references, 1 figure.

  14. The updated RGD Pathway Portal utilizes increased curation efficiency and provides expanded pathway information.

    PubMed

    Hayman, G Thomas; Jayaraman, Pushkala; Petri, Victoria; Tutaj, Marek; Liu, Weisong; De Pons, Jeff; Dwinell, Melinda R; Shimoyama, Mary

    2013-01-01

    The RGD Pathway Portal provides pathway annotations for rat, human and mouse genes and pathway diagrams and suites, all interconnected via the pathway ontology. Diagram pages present the diagram and description, with diagram objects linked to additional resources. A newly-developed dual-functionality web application composes the diagram page. Curators input the description, diagram, references and additional pathway objects. The application combines these with tables of rat, human and mouse pathway genes, including genetic information, analysis tool and reference links, and disease, phenotype and other pathway annotations to pathway genes. The application increases the information content of diagram pages while expediting publication.

  15. Modeling socioeconomic status effects on language development.

    PubMed

    Thomas, Michael S C; Forrester, Neil A; Ronald, Angelica

    2013-12-01

    Socioeconomic status (SES) is an important environmental predictor of language and cognitive development, but the causal pathways by which it operates are unclear. We used a computational model of development to explore the adequacy of manipulations of environmental information to simulate SES effects in English past-tense acquisition, in a data set provided by Bishop (2005). To our knowledge, this is the first application of computational models of development to SES. The simulations addressed 3 new challenges: (a) to combine models of development and individual differences in a single framework, (b) to expand modeling to the population level, and (c) to implement both environmental and genetic/intrinsic sources of individual differences. The model succeeded in capturing the qualitative patterns of regularity effects in both population performance and the predictive power of SES that were observed in the empirical data. The model suggested that the empirical data are best captured by relatively wider variation in learning abilities and relatively narrow variation in (and good quality of) environmental information. There were shortcomings in the model's quantitative fit, which are discussed. The model made several novel predictions, with respect to the influence of SES on delay versus giftedness, the change of SES effects over development, and the influence of SES on children of different ability levels (gene-environment interactions). The first of these predictions was that SES should reliably predict gifted performance in children but not delayed performance, and the prediction was supported by the Bishop data set. Finally, the model demonstrated limits on the inferences that can be drawn about developmental mechanisms on the basis of data from individual differences.

  16. Socioeconomic factors and low birth weight in Mexico

    PubMed Central

    Torres-Arreola, Laura P; Constantino-Casas, Patricia; Flores-Hernández, Sergio; Villa-Barragán, Juan Pablo; Rendón-Macías, Enrique

    2005-01-01

    Background Low birth weight (LBW) is a public health problem linked to lack of equity in populations. Despite efforts to decrease the proportion of newborns with LBW, success has been quite limited. In recent years, studies focused on explaining how social factors influence this problem have shown that populations with greater inequities have a greater proportion of newborns with LBW. Methods The objective was to describe socioeconomic factors related to LBW adjusted by demographic, reproductive and health services variables in Mexico City. A case-control study was carried out in three hospitals with gynaecological and obstetrics services in Mexico City during the first half of 1996. During the recruiting period all children with LBW (cases), defined as newborns weighing <2500 grams, were matched with children born on the same day to control for time of birth. Upon arrival at the hospital for delivery, women were interviewed to determine if they met our inclusion criteria. Women with a history of chronic conditions and those with twin or multiple pregnancies were excluded. Variables with clinical and statistical significance were included in a multivariate model (logistic regression). Results We found that low socioeconomic level was the most important risk factor for LBW and was independent of other factors, including those related to reproduction and nutrition, smoking, morbidity during pregnancy, accessibility to health services and prenatal care (OR 2.68; 95% CI 1.19, 6.03). Conclusion We found that socioeconomic factors are relevant to LBW. However further research should be done in different population groups as well as developing precise ways of measuring socioeconomic factors and their role in reproductive health. PMID:15745443

  17. Socio-Economic Wellbeing in Australian Mining Towns: A Comparative Analysis

    ERIC Educational Resources Information Center

    Tonts, Matthew; Plummer, Paul; Lawrie, Misty

    2012-01-01

    Understanding the links between resource dependence and socio-economic wellbeing has long been a subject of interest amongst social scientists in North America. By contrast, relatively few Australian studies exist on this topic. This is despite the significant role of resource industries in shaping Australia's economic and social geography. Where…

  18. Reading Skill-Fractional Anisotropy Relationships in Visuospatial Tracts Diverge Depending on Socioeconomic Status

    ERIC Educational Resources Information Center

    Gullick, Margaret M.; Demir-Lira, Özlem Ece; Booth, James R.

    2016-01-01

    Low socioeconomic status (SES) has been repeatedly linked with decreased academic achievement, including lower reading outcomes. Some lower SES children do show skills and scores commensurate with those of their higher SES peers, but whether their abilities stem from the same systems as high SES children or are based on divergent strategies is…

  19. Children's Sleep and Cognitive Functioning: Race and Socioeconomic Status as Moderators of Effects

    ERIC Educational Resources Information Center

    Buckhalt, Joseph A.; El-Sheikh, Mona; Keller, Peggy

    2007-01-01

    Race and socioeconomic status (SES) moderated the link between children's sleep and cognitive functioning. One hundred and sixty-six 8- to 9-year-old African and European American children varying in SES participated. Sleep measures were actigraphy, sleep diaries, and self-report; cognitive measures were from the Woodcock-Johnson III and reaction…

  20. Life-course socioeconomic trajectories and diurnal cortisol regulation in adulthood.

    PubMed

    Gustafsson, Per E; Janlert, Urban; Theorell, Töres; Hammarström, Anne

    2010-05-01

    Although the health risk of socioeconomic disadvantage over the life-course is fairly established, the mechanisms are less studied. One candidate pathway is long-term dysregulation of cortisol. This study assesses whether socioeconomic trajectories from adolescence to adulthood influences the regulation of cortisol in mid-adulthood, and further investigates the importance of adolescence as a critical period and of accumulation of socioeconomic disadvantage. Participants were drawn from a 27-year prospective cohort study (n=732, 68% of the original cohort). Information on socioeconomic status (SES) was collected at the ages of 16 (based on parental occupation), 21, 30 and 43 (based on own occupation) years, and at 43 years participants collected one-day salivary cortisol samples at awakening, after 15min, before lunch and at bedtime. We found that the cortisol awakening response (CAR) differed with respect to SES trajectory; those with stable low or early low/upwardly mobile SES tended to display higher CAR than those with early high/downwardly mobile, highly mobile or stable high trajectories. Further analyses revealed that early low SES was related to higher CAR, and in women low SES was related to lower bedtime cortisol, independently of later SES and potential confounders. We found no support for a linear effect of accumulation of socioeconomic disadvantage. In conclusion, our study gives support for an independent effect of low socioeconomic status early in life, on the regulation of cortisol in adulthood. PMID:19879057

  1. The relationship between socio-economic status and cancer detection at screening

    NASA Astrophysics Data System (ADS)

    Taylor-Phillips, Sian; Ogboye, Toyin; Hamborg, Tom; Kearins, Olive; O'Sullivan, Emma; Clarke, Aileen

    2015-03-01

    It is well known that socio-economic status is a strong predictor of screening attendance, with women of higher socioeconomic status more likely to attend breast cancer screening. We investigated whether socio-economic status was related to the detection of cancer at breast screening centres. In two separate projects we combined UK data from the population census, the screening information systems, and the cancer registry. Five years of data from all 81 screening centres in the UK was collected. Only women who had previously attended screening were included. The study was given ethical approval by the University of Warwick Biomedical Research Ethics committee reference SDR-232-07- 2012. Generalised linear models with a log-normal link function were fitted to investigate the relationship between predictors and the age corrected cancer detection rate at each centre. We found that screening centres serving areas with lower average socio-economic status had lower cancer detection rates, even after correcting for the age distribution of the population. This may be because there may be a correlation between higher socio-economic status and some risk factors for breast cancer such as nullparity (never bearing children). When applying adjustment for age, ethnicity and socioeconomic status of the population screened (rather than simply age) we found that SDR can change by up to 0.11.

  2. Socioeconomic Disparities and Prevalence of Autism Spectrum Disorders and Intellectual Disability

    PubMed Central

    Delobel-Ayoub, Malika; Ehlinger, Virginie; Klapouszczak, Dana; Maffre, Thierry; Raynaud, Jean-Philippe; Delpierre, Cyrille; Arnaud, Catherine

    2015-01-01

    Background and Objectives Study of the impact of socioeconomic status on autism spectrum disorders (ASD) and severe intellectual disabilities (ID) has yielded conflicting results. Recent European studies suggested that, unlike reports from the United States, low socioeconomic status is associated with an increased risk of ASD. For intellectual disabilities, the links with socioeconomic status vary according to the severity. We wished to clarify the links between socioeconomic status and the prevalence of ASD (with or without ID) and isolated severe ID. Methods 500 children with ASD and 245 children with severe ID (IQ <50) aged 8 years, born 1995 to 2004, were recruited from a French population-based registry. Inclusions were based on clinical diagnoses reported in medical records according to the International Classification of Diseases, 10th Revision. Socioeconomic status was measured by indicators available at block census level which characterize the population of the child’s area of residence. Measures of deprivation, employment, occupation, education, immigration and family structure were used. Prevalences were compared between groups of census units defined by the tertiles of socioeconomic level in the general population. Results Prevalence of ASD with associated ID was higher in areas with the highest level of deprivation and the highest percentage of unemployed adults, persons with no diploma, immigrants and single-parent families. No association was found when using occupational class. Regarding ASD without associated ID, a higher prevalence was found in areas with the highest percentage of immigrants. No association was found for other socioeconomic indicators. The prevalence of isolated severe ID was likely to be higher in the most disadvantaged groups defined by all indicators. Conclusion The prevalence of ASD with associated ID and of severe isolated ID is more likely to be higher in areas with the highest level of deprivation. PMID:26540408

  3. Community Links

    ERIC Educational Resources Information Center

    Nelson, Mary

    1975-01-01

    At Moraine Valley Community College (Illinois), a chain of events, programs, activities, and services has linked the college and community in such areas as fine arts, ethnic groups, public services, community action, community service, and community education. (Author/NHM)

  4. Link Analysis

    NASA Astrophysics Data System (ADS)

    Donoho, Steve

    Link analysis is a collection of techniques that operate on data that can be represented as nodes and links. This chapter surveys a variety of techniques including subgraph matching, finding cliques and K-plexes, maximizing spread of influence, visualization, finding hubs and authorities, and combining with traditional techniques (classification, clustering, etc). It also surveys applications including social network analysis, viral marketing, Internet search, fraud detection, and crime prevention.

  5. Poverty, Socioeconomic Change, Institutional Anomie, and Homicide*

    PubMed Central

    Kim, Sang-Weon; Pridemore, William Alex

    2006-01-01

    Objective. This study examined institutional anomie theory in the context of transitional Russia. Methods. We employed an index of negative socioeconomic change and measures of family, education, and polity to test the hypothesis that institutional strength conditions the effects of poverty and socioeconomic change on homicide rates. Results. As expected, the results of models estimated using negative binomial regression show direct positive effects of poverty and socioeconomic change and direct negative effects of family strength and polity on regional homicide rates. There was no support, however, for the hypothesis that stronger social institutions reduce the effects of poverty and socioeconomic change on violence. Conclusions. We interpret these results in the Russia-specific setting, concluding that Russia is a rich laboratory for examining the effects of social change on crime and that empirical research in other nations is important when assessing the generalizability of theories developed to explain crime and violence in the United States. PMID:16900262

  6. Poverty, Socioeconomic Change, Institutional Anomie, and Homicide.

    PubMed

    Kim, Sang-Weon; Pridemore, William Alex

    2005-12-01

    Objective. This study examined institutional anomie theory in the context of transitional Russia. Methods. We employed an index of negative socioeconomic change and measures of family, education, and polity to test the hypothesis that institutional strength conditions the effects of poverty and socioeconomic change on homicide rates. Results. As expected, the results of models estimated using negative binomial regression show direct positive effects of poverty and socioeconomic change and direct negative effects of family strength and polity on regional homicide rates. There was no support, however, for the hypothesis that stronger social institutions reduce the effects of poverty and socioeconomic change on violence. Conclusions. We interpret these results in the Russia-specific setting, concluding that Russia is a rich laboratory for examining the effects of social change on crime and that empirical research in other nations is important when assessing the generalizability of theories developed to explain crime and violence in the United States.

  7. Family allowances and fertility: socioeconomic differences.

    PubMed

    Schellekens, Jona

    2009-08-01

    This article explores socioeconomic differences in the effect of family allowances on fertility. Although several studies have examined the relationship between cash benefits and fertility, few studies have addressed the possible differential effects of cash benefits on families of different income or education levels. I reconstructed the birth histories of women in the past two Israeli censuses of 1983 and 1995 to study socioeconomic differences in the effect of family allowances up to the seventh parity. The results indicate that family allowances have a significant effect at every parity. Using female education as an indicator of socioeconomic status, I find that socioeconomic status is a significant modifier of the effect of family allowances. Family allowances seem to have a relatively large impact on more-educated women.

  8. Hair cortisol levels, perceived stress and body mass index in women and children living in socioeconomically disadvantaged neighborhoods: the READI study.

    PubMed

    Olstad, Dana Lee; Ball, Kylie; Wright, Craig; Abbott, Gavin; Brown, Erin; Turner, Anne Isabella

    2016-01-01

    Disadvantaged communities provide adverse psychosocial exposures that have been linked to high levels of stress, and this may provide one explanatory pathway linking socioeconomic disadvantage to obesity. This study used hair cortisol analysis to quantify associations between stress and body mass index (BMI), and between hair cortisol and perceived psychological stress levels, in women and children living in socioeconomically disadvantaged neighborhoods. Participants were a volunteer sample of 70 women from the Resilience for Eating and Activity Despite Inequality study, including 30 maternal-child pairs. Women self-reported body weight, height and perceived psychological stress using the Perceived Stress Scale (PSS), and provided hair samples for themselves and their child. Children's body weight and height were measured. Following extraction, hair cortisol levels were measured using enzyme-linked immunosorbent assay. Multiple linear regression models examined associations between stress and BMI, and between hair cortisol and perceived stress levels in women and children. Women's hair cortisol levels were not associated with their BMI or PSS scores. Women's PSS scores were positively associated with their BMI (p = 0.015). Within maternal-child pairs, mothers and children's hair cortisol levels were strongly positively associated (p = 0.006). Maternal hair cortisol levels and PSS scores were unrelated to their child's zBMI. Children's hair cortisol levels were not associated with their zBMI or with their mother's PSS score. Findings suggest that cortisol-based and perceived psychological measures of stress may be distinct among women and children living in disadvantaged neighborhoods. Perceived psychological measures may be more important predictors of weight-related risk. PMID:27023344

  9. Hair cortisol levels, perceived stress and body mass index in women and children living in socioeconomically disadvantaged neighborhoods: the READI study.

    PubMed

    Olstad, Dana Lee; Ball, Kylie; Wright, Craig; Abbott, Gavin; Brown, Erin; Turner, Anne Isabella

    2016-01-01

    Disadvantaged communities provide adverse psychosocial exposures that have been linked to high levels of stress, and this may provide one explanatory pathway linking socioeconomic disadvantage to obesity. This study used hair cortisol analysis to quantify associations between stress and body mass index (BMI), and between hair cortisol and perceived psychological stress levels, in women and children living in socioeconomically disadvantaged neighborhoods. Participants were a volunteer sample of 70 women from the Resilience for Eating and Activity Despite Inequality study, including 30 maternal-child pairs. Women self-reported body weight, height and perceived psychological stress using the Perceived Stress Scale (PSS), and provided hair samples for themselves and their child. Children's body weight and height were measured. Following extraction, hair cortisol levels were measured using enzyme-linked immunosorbent assay. Multiple linear regression models examined associations between stress and BMI, and between hair cortisol and perceived stress levels in women and children. Women's hair cortisol levels were not associated with their BMI or PSS scores. Women's PSS scores were positively associated with their BMI (p = 0.015). Within maternal-child pairs, mothers and children's hair cortisol levels were strongly positively associated (p = 0.006). Maternal hair cortisol levels and PSS scores were unrelated to their child's zBMI. Children's hair cortisol levels were not associated with their zBMI or with their mother's PSS score. Findings suggest that cortisol-based and perceived psychological measures of stress may be distinct among women and children living in disadvantaged neighborhoods. Perceived psychological measures may be more important predictors of weight-related risk.

  10. Can we monitor socioeconomic inequalities in health? A survey of U.S. health departments' data collection and reporting practices.

    PubMed Central

    Krieger, N; Chen, J T; Ebel, G

    1997-01-01

    OBJECTIVE: To evaluate the potential for and obstacles to routine monitoring of socioeconomic inequalities in health using U.S. vital statistics and disease registry data, the authors surveyed current data collection and reporting practices for specific socioeconomic variables. METHODS: In 1996 the authors mailed a self-administered survey to all of the 55 health department vital statistics offices reporting data to the National Center for Health Statistics (NCHS) to determine what kinds of socioeconomic data they collected on birth and death certificates and in cancer, AIDS, and tuberculosis (TB) registries and what kinds of socioeconomic data were routinely reported in health department publications. RESULTS: Health departments routinely obtained data on occupation on death certificates and in most cancer registries. They collected data on educational level for both birth and death certificates. None of the databases collected information on income, and few obtained data on employment status, health insurance carrier, or receipt of public assistance. When socioeconomic data were collected, they were usually not included in published reports (except for mothers educational level in birth certificate data). Obstacles cited to collecting and reporting socioeconomic data included lack of resources and concerns about the confidentiality and accuracy of data. All databases, however, included residential addresses, suggesting records could be geocoded and linked to Census-based socioeconomic data. CONCLUSIONS: U.S. state and Federal vital statistics and disease registries should routinely collect and publish socioeconomic data to improve efforts to monitor trends in and reduce social inequalities in health. PMID:10822475

  11. Updating the Wnt pathways

    PubMed Central

    Yu, Jia; Virshup, David M.

    2014-01-01

    In the three decades since the discovery of the Wnt1 proto-oncogene in virus-induced mouse mammary tumours, our understanding of the signalling pathways that are regulated by the Wnt proteins has progressively expanded. Wnts are involved in an complex signalling network that governs multiple biological processes and cross-talk with multiple additional signalling cascades, including the Notch, FGF (fibroblast growth factor), SHH (Sonic hedgehog), EGF (epidermal growth factor) and Hippo pathways. The Wnt signalling pathway also illustrates the link between abnormal regulation of the developmental processes and disease manifestation. Here we provide an overview of Wnt-regulated signalling cascades and highlight recent advances. We focus on new findings regarding the dedicated Wnt production and secretion pathway with potential therapeutic targets that might be beneficial for patients with Wnt-related diseases. PMID:25208913

  12. Social consequences of early socioeconomic adversity and youth BMI trajectories: gender and race/ethnicity differences.

    PubMed

    Bae, Dayoung; Wickrama, K A S; O'Neal, Catherine Walker

    2014-08-01

    The present study investigated the mediating effects of adolescent BMI trajectories on socioeconomic continuity over the early life course using a nationally representative sample of 11,075 respondents. This study considered both the initial severity as well as change over time in BMI as psycho-physiological mediators. Consistent with the life course pathway model and the cumulative advantage and disadvantage principle, the results suggested that early socioeconomic adversity is associated with youth BMI trajectories over time, which in turn, impair young adult socioeconomic attainment. The results also revealed important gender and racial/ethnic differences in the hypothesized associations. These findings elucidate how early adversity exerts an enduring long-term influence on social attainment in young adulthood. Further, the findings suggest that effective obesity intervention and prevention programs should focus not only on the severity of obesity but also on growth in BMI over the early years.

  13. Change in Neighborhood Socioeconomic Status and Weight Gain

    PubMed Central

    Powell-Wiley, Tiffany M.; Cooper-McCann, Rebecca; Ayers, Colby; Berrigan, David; Lian, Min; McClurkin, Michael; Barbash, Rachel Ballard; Das, Sandeep R.; Hoehner, Christine M.; Leonard, Tammy

    2015-01-01

    Introduction Despite a proposed connection between neighborhood environment and obesity, few longitudinal studies have examined the relationship between change in neighborhood socioeconomic deprivation, as defined by moving between neighborhoods, and change in body weight. The purpose of this study is to examine the longitudinal relationship between moving to more socioeconomically deprived neighborhoods and weight gain as a cardiovascular risk factor. Methods Weight (kg) was measured in the Dallas Heart Study (DHS), a multiethnic cohort aged 18–65 years, at baseline (2000–2002) and 7-year follow-up (2007–2009, N=1,835). Data were analyzed in 2013–2014. Geocoded addresses were linked to Dallas County, TX census block groups. A block group-level neighborhood deprivation index (NDI) was created. Multilevel difference-in-difference models with random effects and a Heckman correction factor (HCF) determined weight change relative to NDI change. Results Forty-nine percent of the DHS population moved (263 to higher NDI, 586 to lower NDI, 47 within same NDI), with blacks more likely to move than whites or Hispanics (p<0.01), but similar baseline BMI and waist circumference were observed in movers vs. non-movers (p>0.05). Adjusting for HCF, sex, race, and time-varying covariates, those who moved to areas of higher NDI gained more weight compared to those remaining in the same or moving to a lower NDI (0.64 kg per 1-unit NDI increase, 95% CI=0.09, 1.19). Impact of NDI change on weight gain increased with time (p=0.03). Conclusions Moving to more–socioeconomically deprived neighborhoods was associated with weight gain among DHS participants. PMID:25960394

  14. Cultural pathways through universal development.

    PubMed

    Greenfield, Patricia M; Keller, Heidi; Fuligni, Andrew; Maynard, Ashley

    2003-01-01

    We focus our review on three universal tasks of human development: relationship formation, knowledge acquisition, and the balance between autonomy and relatedness at adolescence. We present evidence that each task can be addressed through two deeply different cultural pathways through development: the pathways of independence and interdependence. Whereas core theories in developmental psychology are universalistic in their intentions, they in fact presuppose the independent pathway of development. Because the independent pathway is therefore well-known in psychology, we focus a large part of our review on empirically documenting the alternative, interdependent pathway for each developmental task. We also present three theoretical approaches to culture and development: the ecocultural, the sociohistorical, and the cultural values approach. We argue that an understanding of cultural pathways through human development requires all three approaches. We review evidence linking values (cultural values approach), ecological conditions (ecocultural approach), and socialization practices (sociohistorical approach) to cultural pathways through universal developmental tasks. PMID:12415076

  15. Socioeconomic Differences in Informed Decisions About Down Syndrome Screening: A Systematic Review and Research Agenda.

    PubMed

    Smith, Sian K; Sousa, Mariana S; Essink-Bot, Marie-Louise; Halliday, Jane; Peate, Michelle; Fransen, Mirjam

    2016-08-01

    Supporting pregnant women to make informed choices about Down syndrome screening is widely endorsed. We reviewed the literature on: (a) the association between socioeconomic position and informed choices and decision-making about Down syndrome screening, and (b) the possible mediating variables (e.g., health literacy, numeracy skills, behavioral and communication variables) that might explain the relationship. EMBASE, MEDLINE, PubMed, CINAHL, and PsycINFO were searched from January 1999 to September 2014. The methodological quality of studies was determined by predefined criteria regarding the research aims, study design, study population and setting, measurement tools, and statistical analysis. A total of 33 studies met the inclusion criteria. Women from lower socioeconomic groups experience greater difficulties making informed choices about Down syndrome screening compared to women from higher socioeconomic groups. Most studies focus on individual dimensions of informed decision-making rather than assessing elements in conjunction with one another. Few studies have explored why there are socioeconomic differences in women's ability to make informed screening decisions. Future work is needed to identify mediating variables in this pathway. Systematic evidence-based intervention development to improve communication, understanding, and decision-making about Down syndrome screening is needed to ensure that women have an equal opportunity to make an informed choice about screening regardless of their socioeconomic position. PMID:27410478

  16. Income inequality, parental socioeconomic status, and birth outcomes in Japan.

    PubMed

    Fujiwara, Takeo; Ito, Jun; Kawachi, Ichiro

    2013-05-15

    The purpose of this study was to investigate the impact of income inequality and parental socioeconomic status on several birth outcomes in Japan. Data were collected on birth outcomes and parental socioeconomic status by questionnaire from Japanese parents nationwide (n = 41,499) and then linked to Gini coefficients at the prefectural level in 2001. In multilevel analysis, z scores of birth weight for gestational age decreased by 0.018 (95% confidence interval (CI): -0.029, -0.006) per 1-standard-deviation (0.018-unit) increase in the Gini coefficient, while gestational age at delivery was not associated with the Gini coefficient. For dichotomous outcomes, mothers living in prefectures with middle and high Gini coefficients were 1.24 (95% CI: 1.05, 1.47) and 1.23 (95% CI: 1.02, 1.48) times more likely, respectively, to deliver a small-for-gestational-age infant than mothers living in more egalitarian prefectures (low Gini coefficients), although preterm births were not significantly associated with income distribution. Parental educational level, but not household income, was significantly associated with the z score of birth weight for gestational age and small-for-gestational-age status. Higher income inequality at the prefectural level and parental educational level, rather than household income, were associated with intrauterine growth but not with shorter gestational age at delivery.

  17. Racial and socioeconomic factors in glomerular disease.

    PubMed

    Halevy, D; Radhakrishnan, J; Appel, G B

    2001-07-01

    The influence of racial and socioeconomic factors on the incidence, prognosis, and response to therapy of many diseases has long been noted. Although glomerular diseases comprise 10% to over 16% of the dialysis and renal transplant populations, respectively, only recently have racial and socioeconomic factors been evaluated. Several glomerular diseases are associated with a striking African-American predominance. These include idiopathic focal sclerosis, and especially its collapsing variant, human immunodeficiency virus (HIV)-associated nephropathy, and severe lupus nephritis. In many of these entities the renal disease is also more aggressive and rapidly progressive than in other populations. Recent data points to genetic-biologic as well as social and economic factors that may be responsible for these findings. Studies dealing with the therapy of glomerular lesions must be stratified for racial and social background differences to avoid bias in outcome. Whether racial and socioeconomic data should be used in treating individual patients, and how, remains an area of controversy.

  18. Association between Socioeconomic Factors and Cancer Risk: A Population Cohort Study in Scotland (1991-2006)

    PubMed Central

    Sharpe, Katharine H.; McMahon, Alex D.; Raab, Gillian M.; Brewster, David H.; Conway, David I.

    2014-01-01

    Background Lung and upper aero-digestive tract (UADT) cancer risk are associated with low socioeconomic circumstances and routinely measured using area socioeconomic indices. We investigated effect of country of birth, marital status, one area deprivation measure and individual socioeconomic variables (economic activity, education, occupational social class, car ownership, household tenure) on risk associated with lung, UADT and all cancer combined (excluding non melanoma skin cancer). Methods We linked Scottish Longitudinal Study and Scottish Cancer Registry to follow 203,658 cohort members aged 15+ years from 1991–2006. Relative risks (RR) were calculated using Poisson regression models by sex offset for person-years of follow-up. Results 21,832 first primary tumours (including 3,505 lung, 1,206 UADT) were diagnosed. Regardless of cancer, economically inactivity (versus activity) was associated with increased risk (male: RR 1.14, 95% CI 1.10–1.18; female: RR 1.06, 95% CI 1.02–1.11). For lung cancer, area deprivation remained significant after full adjustment suggesting the area deprivation cannot be fully explained by individual variables. No or non degree qualification (versus degree) was associated with increased lung risk; likewise for UADT risk (females only). Occupational social class associations were most pronounced and elevated for UADT risk. No car access (versus ownership) was associated with increased risk (excluding all cancer risk, males). Renting (versus home ownership) was associated with increased lung cancer risk, UADT cancer risk (males only) and all cancer risk (females only). Regardless of cancer group, elevated risk was associated with no education and living in deprived areas. Conclusions Different and independent socioeconomic variables are inversely associated with different cancer risks in both sexes; no one socioeconomic variable captures all aspects of socioeconomic circumstances or life course. Association of multiple

  19. ICT reuse in socio-economic enterprises

    SciTech Connect

    Ongondo, F.O.; Williams, I.D.; Dietrich, J.; Carroll, C.

    2013-12-15

    Highlights: • We analyse ICT equipment reuse operations of socio-economic enterprises. • Most common ICT products dealt with are computers and related equipment. • In the UK in 2010, ∼143,750 appliances were reused. • Marketing and legislative difficulties are the common hurdles to reuse activities. • Socio-economic enterprises can significantly contribute to resource efficiency. - Abstract: In Europe, socio-economic enterprises such as charities, voluntary organisations and not-for-profit companies are involved in the repair, refurbishment and reuse of various products. This paper characterises and analyses the operations of socio-economic enterprises that are involved in the reuse of Information and Communication Technology (ICT) equipment. Using findings from a survey, the paper specifically analyses the reuse activities of socio-economic enterprises in the UK from which Europe-wide conclusions are drawn. The amount of ICT products handled by the reuse organisations is quantified and potential barriers and opportunities to their operations are analysed. By-products from reuse activities are discussed and recommendations to improve reuse activities are provided. The most common ICT products dealt with by socio-economic enterprises are computers and related equipment. In the UK in 2010, an estimated 143,750 appliances were reused. However, due to limitations in data, it is difficult to compare this number to the amount of new appliances that entered the UK market or the amount of waste electrical and electronic equipment generated in the same period. Difficulties in marketing products and numerous legislative requirements are the most common barriers to reuse operations. Despite various constraints, it is clear that organisations involved in reuse of ICT could contribute significantly to resource efficiency and a circular economy. It is suggested that clustering of their operations into “reuse parks” would enhance both their profile and their

  20. Allostatic load: a mechanism of socioeconomic health disparities?

    PubMed

    Szanton, Sarah L; Gill, Jessica M; Allen, Jerilyn K

    2005-07-01

    Although research on health disparities has been prioritized by the National Institutes of Health, the Institute of Medicine, and Healthy People 2010, little has been published that examines the biology underlying health disparities. Allostatic load is a multisystem construct theorized to quantify stress-induced biological risk. Differences in allostatic load may reflect differences in stress exposure and thus provide a mechanistic link to understanding health disparities. The purpose of this systematic review is to examine the construct of allostatic load and the published studies that employ it in an effort to understand whether the construct can be useful in quantifying health disparities. The published literature demonstrates that allostatic load is elevated in those of low socioeconomic status (SES) as compared to those of high SES. The reviewed articles vary in the justification for inclusion of variables. Recommendations for future research are made in the contexts of measurement, methodology, and racial composition of participants.

  1. Pathways to chromothripsis.

    PubMed

    Ivkov, Robert; Bunz, Fred

    2015-01-01

    Chromothripsis is a recently recognized mode of genetic instability that generates chromosomes with strikingly large numbers of segmental re-arrangements. While the characterization of these derivative chromosomes has provided new insights into the processes by which cancer genomes can evolve, the underlying signaling events and molecular mechanisms remain unknown. In medulloblastomas, chromothripsis has been observed to occur in the context of mutational inactivation of p53 and activation of the canonical Hedgehog (Hh) pathway. Recent studies have illuminated mechanistic links between these 2 signaling pathways, including a novel PTCH1 homolog that is regulated by p53. Here, we integrate this new pathway into a hypothetical model for the catastrophic DNA breakage that appears to trigger profound chromosomal rearrangements. PMID:26178348

  2. Postfamine stature and socioeconomic status in Ireland.

    PubMed

    Young, Kristin; Relethford, John H; Crawford, Michael H

    2008-01-01

    Previous research has documented socioeconomic stratification of secular trend in height in historical populations. Using data from 4,900 males and 1,430 females born between 1840 and 1910 collected as part of the Harvard Anthropological Survey of Ireland (1934-1936), this study examined the secular changes in postfamine Ireland using several socioeconomic variables, including: occupation, migration, education, siblings, birthplace, and occupation of father and mother's father. Correlations were also calculated between height and various historical economic indices. Significant differences in the height of Irish males were found by occupation, education, and socioeconomic status of father and maternal grandfather. Males employed in agriculture, or whose fathers or grandfathers were so employed, were significantly taller than other males. For the smaller female sample, only occupation and grandfather's socioeconomic status had a significant impact on height. An inverse correlation was also found between the British Cost of Living Index (BCL) and male heights. Our results suggest that availability of resources plays an important role in the overall nutritional status reflected in terminal adult height.

  3. Socioeconomic Status and Cultural Influences on Language

    ERIC Educational Resources Information Center

    Hoff, E.; Tian, C.

    2005-01-01

    Two studies track connections from the distal variables of socioeconomic status (SES) and culture to properties of the interactions children experience and to the rate of children's language development. The first study is an investigation of the relations among family SES, properties of maternal child-directed speech, and child vocabulary growth…

  4. A Study of Suicide and Socioeconomic Factors

    ERIC Educational Resources Information Center

    Ying, Yung-hsiang; Chang, Koyin

    2009-01-01

    The topic of suicide has long been an important socioeconomic issue studied in many countries. Suicides inject an atmosphere of unrest into society, and media attention furthers that social uneasiness. From the viewpoint of economics and management, suicide is a waste of human resource: it decreases the labor force in society and deteriorates…

  5. Socioeconomic Disparities Affect Prefrontal Function in Children

    ERIC Educational Resources Information Center

    Kishiyama, Mark M.; Boyce, W. Thomas; Jimenez, Amy M.; Perry, Lee M.; Knight, Robert T.

    2009-01-01

    Social inequalities have profound effects on the physical and mental health of children. Children from low socioeconomic status (SES) backgrounds perform below children from higher SES backgrounds on tests of intelligence and academic achievement, and recent findings indicate that low SES (LSES) children are impaired on behavioral measures of…

  6. Socio-Economic Diversity and Mathematical Competences

    ERIC Educational Resources Information Center

    Thiel, Oliver

    2012-01-01

    The Programme for International Student Assessment (PISA) has proved that in Germany the impact that socio-economic background has on 15-year-old pupils' achievement is stronger than in other countries. The Progress in International Reading Literacy Study (PIRLS) showed that the correlation is less with 10-year-old children, but is still apparent.…

  7. Socioeconomic Heterogeneity of Mining-Dependent Counties.

    ERIC Educational Resources Information Center

    Nord, Mark; Luloff, A. E.

    1993-01-01

    Although the socioeconomic well-being of all U.S. mining-dependent counties was slightly above the national average in 1990, disaggregation reveals substantial effects of region and mining subsector. In particular, southern and Great Lakes coal-mining counties had significantly lower high school graduation rates and higher poverty and unemployment…

  8. Socioeconomic Status, Parenting, and Child Development.

    ERIC Educational Resources Information Center

    Bornstein, Marc H., Ed.; Bradley, Robert H., Ed.

    Noting that there is near universal agreement that children from families with higher socioeconomic status (SES) have access to more of the resources needed to support their positive development than do lower SES children, this monograph examines the myriad questions remaining regarding relations among SES, parenting, and child development from a…

  9. College Enhancement Strategies and Socioeconomic Inequality

    ERIC Educational Resources Information Center

    Wolniak, Gregory C.; Wells, Ryan S.; Engberg, Mark E.; Manly, Catherine A.

    2016-01-01

    The study provides new information on the relationships between students' socioeconomic backgrounds, utilization of college enhancement strategies, and subsequent 4-year college enrollment. Enhancement strategies represent student behaviors used to bolster the competitiveness of a college application, such as Advanced Placement exams and a variety…

  10. Tumor necrosis factor receptor-associated factor-6 and ribosomal S6 kinase intracellular pathways link the angiotensin II AT1 receptor to the phosphorylation and activation of the IkappaB kinase complex in vascular smooth muscle cells.

    PubMed

    Doyon, Priscilla; Servant, Marc J

    2010-10-01

    Activation of NF-κB transcription factors by locally produced angiotensin II (Ang II) is proposed to be involved in chronic inflammatory reactions leading to atherosclerosis development. However, a clear understanding of the signaling cascades coupling the Ang II AT1 receptors to the activation of NF-κB transcription factors is still lacking. Using primary cultured aortic vascular smooth muscle cells, we show that activation of the IKK complex and NF-κB transcription factors by Ang II is regulated by phosphorylation of the catalytic subunit IKKβ on serine residues 177 and 181 in the activation T-loop. The use of pharmacological inhibitors against conventional protein kinases C (PKCs), mitogen-activated/extracellular signal-regulated kinase (MEK) 1/2, ribosomal S6 kinase (RSK), and silencing RNA technology targeting PKCα, IKKβ subunit, tumor growth factor β-activating kinase-1 (TAK1), the E3 ubiquitin ligase tumor necrosis factor receptor-associated factor-6 (TRAF6), and RSK isoforms, demonstrates the requirement of two distinct signaling pathway for the phosphorylation of IKKβ and the activation of the IKK complex by Ang II. Rapid phosphorylation of IKKβ requires a second messenger-dependent pathway composed of PKCα-TRAF6-TAK1, whereas sustained phosphorylation and activation of IKKβ requires the MEK1/2-ERK1/2-RSK pathway. Importantly, simultaneously targeting components of these two pathways completely blunts the phosphorylation of IKKβ and the proinflammatory effect of the octapeptide. This is the first report demonstrating activation of TAK1 by the AT1R. We propose a model whereby TRAF6-TAK1 and ERK-RSK intracellular pathways independently and sequentially converge to the T-loop phosphorylation for full activation of IKKβ, which is an essential step in the proinflammatory activity of Ang II.

  11. WikiPathways: capturing the full diversity of pathway knowledge

    PubMed Central

    Kutmon, Martina; Riutta, Anders; Nunes, Nuno; Hanspers, Kristina; Willighagen, Egon L.; Bohler, Anwesha; Mélius, Jonathan; Waagmeester, Andra; Sinha, Sravanthi R.; Miller, Ryan; Coort, Susan L.; Cirillo, Elisa; Smeets, Bart; Evelo, Chris T.; Pico, Alexander R.

    2016-01-01

    WikiPathways (http://www.wikipathways.org) is an open, collaborative platform for capturing and disseminating models of biological pathways for data visualization and analysis. Since our last NAR update, 4 years ago, WikiPathways has experienced massive growth in content, which continues to be contributed by hundreds of individuals each year. New aspects of the diversity and depth of the collected pathways are described from the perspective of researchers interested in using pathway information in their studies. We provide updates on extensions and services to support pathway analysis and visualization via popular standalone tools, i.e. PathVisio and Cytoscape, web applications and common programming environments. We introduce the Quick Edit feature for pathway authors and curators, in addition to new means of publishing pathways and maintaining custom pathway collections to serve specific research topics and communities. In addition to the latest milestones in our pathway collection and curation effort, we also highlight the latest means to access the content as publishable figures, as standard data files, and as linked data, including bulk and programmatic access. PMID:26481357

  12. Library links on medical school home pages.

    PubMed

    Thomas, Sheila L

    2011-01-01

    The purpose of this study was to assess the websites of American Association of Medical Colleges (AAMC)-member medical schools for the presence of library links. Sixty-one percent (n = 92) of home pages of the 150 member schools of the AAMC contain library links. For the 58 home pages not offering such links, 50 provided a pathway of two or three clicks to a library link. The absence of library links on 39% of AAMC medical school home pages indicates that the designers of those pages did not consider the library to be a primary destination for their visitors.

  13. ICT reuse in socio-economic enterprises.

    PubMed

    Ongondo, F O; Williams, I D; Dietrich, J; Carroll, C

    2013-12-01

    In Europe, socio-economic enterprises such as charities, voluntary organisations and not-for-profit companies are involved in the repair, refurbishment and reuse of various products. This paper characterises and analyses the operations of socio-economic enterprises that are involved in the reuse of Information and Communication Technology (ICT) equipment. Using findings from a survey, the paper specifically analyses the reuse activities of socio-economic enterprises in the U.K. from which Europe-wide conclusions are drawn. The amount of ICT products handled by the reuse organisations is quantified and potential barriers and opportunities to their operations are analysed. By-products from reuse activities are discussed and recommendations to improve reuse activities are provided. The most common ICT products dealt with by socio-economic enterprises are computers and related equipment. In the U.K. in 2010, an estimated 143,750 appliances were reused. However, due to limitations in data, it is difficult to compare this number to the amount of new appliances that entered the U.K. market or the amount of waste electrical and electronic equipment generated in the same period. Difficulties in marketing products and numerous legislative requirements are the most common barriers to reuse operations. Despite various constraints, it is clear that organisations involved in reuse of ICT could contribute significantly to resource efficiency and a circular economy. It is suggested that clustering of their operations into "reuse parks" would enhance both their profile and their products. Reuse parks would also improve consumer confidence in and subsequently sales of the products. Further, it is advocated that industrial networking opportunities for the exchange of by-products resulting from the organisations' activities should be investigated. The findings make two significant contributions to the current literature. One, they provide a detailed insight into the reuse operations

  14. ICT reuse in socio-economic enterprises.

    PubMed

    Ongondo, F O; Williams, I D; Dietrich, J; Carroll, C

    2013-12-01

    In Europe, socio-economic enterprises such as charities, voluntary organisations and not-for-profit companies are involved in the repair, refurbishment and reuse of various products. This paper characterises and analyses the operations of socio-economic enterprises that are involved in the reuse of Information and Communication Technology (ICT) equipment. Using findings from a survey, the paper specifically analyses the reuse activities of socio-economic enterprises in the U.K. from which Europe-wide conclusions are drawn. The amount of ICT products handled by the reuse organisations is quantified and potential barriers and opportunities to their operations are analysed. By-products from reuse activities are discussed and recommendations to improve reuse activities are provided. The most common ICT products dealt with by socio-economic enterprises are computers and related equipment. In the U.K. in 2010, an estimated 143,750 appliances were reused. However, due to limitations in data, it is difficult to compare this number to the amount of new appliances that entered the U.K. market or the amount of waste electrical and electronic equipment generated in the same period. Difficulties in marketing products and numerous legislative requirements are the most common barriers to reuse operations. Despite various constraints, it is clear that organisations involved in reuse of ICT could contribute significantly to resource efficiency and a circular economy. It is suggested that clustering of their operations into "reuse parks" would enhance both their profile and their products. Reuse parks would also improve consumer confidence in and subsequently sales of the products. Further, it is advocated that industrial networking opportunities for the exchange of by-products resulting from the organisations' activities should be investigated. The findings make two significant contributions to the current literature. One, they provide a detailed insight into the reuse operations

  15. Educational Justice and Socio-Economic Segregation in Schools

    ERIC Educational Resources Information Center

    Brighouse, Harry

    2007-01-01

    Sociologists exploring educational injustice often focus on socio-economic segregation as a central measure of injustice. The comprehensive ideal, furthermore, has the idea of socio-economic integration built into it. The current paper argues that socio-economic segregation is valuable only insofar as it serves other, more fundamental values. This…

  16. Information for Innovation and Socioeconomic Development

    NASA Astrophysics Data System (ADS)

    Pearlman, F.; Stewart, M. A.

    2013-12-01

    This presentation reviews and extends the results of a workshop held in Florence, Italy in June 2013. This was the latest in a series of workshops on the 'Socioeconomic Benefits of Environmental Information'. The focus of this workshops included: 1. Information (Earth Observation, geospatial data, community generated data) as a driver for economic and social development, including measures of well-being that move beyond GDP as an indicator 2. Economic impact of innovations stemming from Open Data and the re-use of Public Sector Information 3. Importance of communications to reach across disciplines from scientists to citizen-scientists to end-users. Keynote addresses highlighted the state of the art, in this multi-disciplinary field and introduced the three themes above. The workshop included several panel discussions addressing key approaches to analyzing and understanding socioeconomic impacts. . This presentation extracts the key elements from the discussions and analyzes paths forward for improved impact assessments.

  17. Neighborhood socioeconomic deprivation, perceived neighborhood factors, and cortisol responses to induced stress among healthy adults.

    PubMed

    Barrington, Wendy E; Stafford, Mai; Hamer, Mark; Beresford, Shirley A A; Koepsell, Thomas; Steptoe, Andrew

    2014-05-01

    Associations between measures of neighborhood socioeconomic deprivation and health have been identified, yet work is needed to uncover explanatory mechanisms. One hypothesized pathway is through stress, yet the few studies that have evaluated associations between characteristics of deprived neighborhoods and biomarkers of stress are mixed. This study evaluated whether objectively measured neighborhood socioeconomic deprivation and individual perceived neighborhood characteristics (i.e. social control and fear of crime) impacted cortisol responses to an induced stressor among older healthy adults. Data from Heart Scan, a sub-study of the Whitehall II cohort, were used to generate multilevel piecewise growth-curve models of cortisol trajectories after a laboratory stressor accounting for neighborhood and demographic characteristics. Neighborhood socioeconomic deprivation was significantly associated with individual perceptions of social control and fear of crime in the neighborhood while an association with blunted cortisol reactivity was only evidence among women. Social control was significantly associated with greater cortisol reactivity and mediation between neighborhood socioeconomic deprivation and cortisol reactivity was suggested among women. These findings support a gender-dependent role of neighborhood in stress process models of health. PMID:24603009

  18. Neighborhood socioeconomic deprivation, perceived neighborhood factors, and cortisol responses to induced stress among healthy adults.

    PubMed

    Barrington, Wendy E; Stafford, Mai; Hamer, Mark; Beresford, Shirley A A; Koepsell, Thomas; Steptoe, Andrew

    2014-05-01

    Associations between measures of neighborhood socioeconomic deprivation and health have been identified, yet work is needed to uncover explanatory mechanisms. One hypothesized pathway is through stress, yet the few studies that have evaluated associations between characteristics of deprived neighborhoods and biomarkers of stress are mixed. This study evaluated whether objectively measured neighborhood socioeconomic deprivation and individual perceived neighborhood characteristics (i.e. social control and fear of crime) impacted cortisol responses to an induced stressor among older healthy adults. Data from Heart Scan, a sub-study of the Whitehall II cohort, were used to generate multilevel piecewise growth-curve models of cortisol trajectories after a laboratory stressor accounting for neighborhood and demographic characteristics. Neighborhood socioeconomic deprivation was significantly associated with individual perceptions of social control and fear of crime in the neighborhood while an association with blunted cortisol reactivity was only evidence among women. Social control was significantly associated with greater cortisol reactivity and mediation between neighborhood socioeconomic deprivation and cortisol reactivity was suggested among women. These findings support a gender-dependent role of neighborhood in stress process models of health.

  19. Income Inequality and Socioeconomic Gradients in Mortality

    PubMed Central

    Wilkinson, Richard G.; Pickett, Kate E.

    2008-01-01

    Objectives. We investigated whether the processes underlying the association between income inequality and population health are related to those responsible for the socioeconomic gradient in health and whether health disparities are smaller when income differences are narrower. Methods. We used multilevel models in a regression analysis of 10 age- and cause-specific US county mortality rates on county median household incomes and on state income inequality. We assessed whether mortality rates more closely related to county income were also more closely related to state income inequality. We also compared mortality gradients in more- and less-equal states. Results. Mortality rates more strongly associated with county income were more strongly associated with state income inequality: across all mortality rates, r= −0.81; P=.004. The effect of state income inequality on the socioeconomic gradient in health varied by cause of death, but greater equality usually benefited both wealthier and poorer counties. Conclusions. Although mortality rates with steep socioeconomic gradients were more sensitive to income distribution than were rates with flatter gradients, narrower income differences benefit people in both wealthy and poor areas and may, paradoxically, do little to reduce health disparities. PMID:17901426

  20. Strongyloidiasis: A Disease of Socioeconomic Disadvantage

    PubMed Central

    Beknazarova, Meruyert; Whiley, Harriet; Ross, Kirstin

    2016-01-01

    Strongyloidiasis is a disease caused by soil transmitted helminths of the Strongyloides genus. Currently, it is predominately described as a neglected tropical disease. However, this description is misleading as it focuses on the geographical location of the disease and not the primary consideration, which is the socioeconomic conditions and poor infrastructure found within endemic regions. This classification may result in misdiagnosis and mistreatment by physicians, but more importantly, it influences how the disease is fundamentally viewed. Strongyloidiasis must be first and foremost considered as a disease of disadvantage, to ensure the correct strategies and control measures are used to prevent infection. Changing how strongyloidiasis is perceived from a geographic and clinical issue to an environmental health issue represents the first step in identifying appropriate long term control measures. This includes emphasis on environmental health controls, such as better infrastructure, sanitation and living conditions. This review explores the global prevalence of strongyloidiasis in relation to its presence in subtropical, tropical and temperate climate zones with mild and cold winters, but also explores the corresponding socioeconomic conditions of these regions. The evidence shows that strongyloidiasis is primarily determined by the socioeconomic status of the communities rather than geographic or climatic conditions. It demonstrates that strongyloidiasis should no longer be referred to as a “tropical” disease but rather a disease of disadvantage. This philosophical shift will promote the development of correct control strategies for preventing this disease of disadvantage. PMID:27213420

  1. Intergenerational and socioeconomic gradients of child obesity.

    PubMed

    Costa-Font, Joan; Gil, Joan

    2013-09-01

    Can the rise in obesity among children be attributed to the intergenerational transmission of parental influences? Does this trend affect the influence of parent's socioeconomic status on obesity? This paper documents evidence of an emerging social gradient of obesity in pre-school children resulting from a combination of both socio-economic status and less intensive childcare associated with maternal employment, when different forms of intergenerational transmission are controlled for. We also estimate and decompose income related inequalities in child obesity. We take advantage of a uniquely constructed dataset from Spain that contains records form 13,358 individuals for a time period (years 2003-2006) in which a significant spike in the growth of child obesity was observed. Our results suggest robust evidence of both socioeconomic and intergenerational gradients. Results are suggestive of a high income effect in child obesity, alongside evidence that income inequalities have doubled in just three years with a pure income effect accounting for as much as 72-66% of these income inequality estimates, even when intergenerational transmission is accounted for. Although, intergenerational transmission does not appear to be gender specific, when accounted for, mother's labour market participation only explains obesity among boys but not among girls. Hence, it appears income and parental influences are the central determinants of obesity among children.

  2. High School Physics Offerings by Socioeconomic Profile

    NASA Astrophysics Data System (ADS)

    2011-12-01

    This fall we have been examining physics classes in U.S. high schools by the principal's assessment of the socioeconomic profile of each school. This month we turn our focus to the distribution of high school physics enrollment across the different types of physics offered. Not only do fewer students take physics at "worse off" schools (see the October issue), but the types of physics courses students take also differs by socioeconomic profile. About 10% of the students taking physics at "worse off" schools take AP and second-year physics; almost 20% of the students at "better off" schools take these courses. At "worse off" schools, a higher proportion of students are enrolled in conceptual courses, including Physics First and regular physics taught using a conceptual textbook. The data we have presented over the last four months suggests that differences in physics taking in high school by blacks and Hispanics are driven, in part, by underlying socioeconomic factors. Other factors, such as the availability of additional seats in physics classes and the ability of teachers to attract students to physics, also impact physics taking. It is unlikely that the racial and ethnic differences in physics taking in high school will decrease unless the underlying factors are addressed.

  3. Socio-economic Inequality in the Use of Procedures and Mortality Among AMI Patients: Quantifying the Effects Along Different Paths.

    PubMed

    Hagen, Terje P; Häkkinen, Unto; Iversen, Tor; Klitkou, Søren Toksvig; Moger, Tron Anders

    2015-12-01

    It is not known whether inequality in access to cardiac procedures translates into inequality in mortality. In this paper, we use a path analysis model to quantify both the direct effect of socio-economic status on mortality and the indirect effect of socio-economic status on mortality as mediated by the provision of cardiac procedures. The study links microdata from the Finnish and Norwegian national patient registers describing treatment episodes with data from prescription registers, causes-of-death registers and registers covering education and income. We show that socio-economic variables affect access to percutaneous coronary intervention in both countries, but that these effects are only moderate and that the indirect effects of the socio-economic factors on mortality through access to percutaneous coronary intervention are minor. The direct effects of income and education on mortality are significantly larger. We conclude that the socio-economic gradient in the use of percutaneous coronary intervention adds to socio-economic differences in mortality to little or no extent. PMID:26633871

  4. Understanding the relationship between socioeconomic status, smoking cessation services provided by the health system and smoking cessation behavior in Brazil.

    PubMed

    Szklo, André Salem; Thrasher, James F; Perez, Cristina; Figueiredo, Valeska Carvalho; Fong, Geoffrey; Almeida, Liz Maria de

    2013-03-01

    Increasing the effectiveness of smoking cessation policies requires greater consideration of the cultural and socioeconomic complexities of smoking. The purpose of this paper is to explore the association between socioeconomic status and "selected midpoints" linked to smoking cessation in Brazil. Data was collected from a representative sample of urban adult smokers as part of the ITC-Brazil Survey (2009, N = 1,215). After controlling for age and gender, there were no statistically significant differences quit attempts in the last six months between individuals with different socioeconomic status. However, smokers with high socioeconomic status visited a doctor 1.54 times more often than those with low socioeconomic status (p-value = 0.017), and were also 1.65 times more likely to receive advice to quit smoking (p-value = 0.025). Our results demonstrate that disparities in health and socioeconomic status are still a major challenge for policymakers to increase the population impact of tobacco control actions worldwide.

  5. Socioeconomic and Sociodemographic Factors Associated with Asthma Related Outcomes in Early Childhood: The Generation R Study

    PubMed Central

    Hafkamp-de Groen, Esther; Sonnenschein-van der Voort, Agnes M. M.; Mackenbach, Johan P.; Duijts, Liesbeth; Jaddoe, Vincent W. V.; Moll, Henriëtte A.; Hofman, Albert; de Jongste, Johan C.; Raat, Hein

    2013-01-01

    encourage further studies on underlying pathways and public health intervention programs, focusing on reducing socioeconomic or sociodemographic inequalities in asthma. PMID:24244299

  6. Targeting Wnt pathways in disease.

    PubMed

    Zimmerman, Zachary F; Moon, Randall T; Chien, Andy J

    2012-11-01

    Wnt-mediated signal transduction pathways have long been recognized for their roles in regulating embryonic development, and have more recently been linked to cancer, neurologic diseases, inflammatory diseases, and disorders of endocrine function and bone metabolism in adults. Although therapies targeting Wnt signaling are attractive in theory, in practice it has been difficult to obtain specific therapeutics because many components of Wnt signaling pathways are also involved in other cellular processes, thereby reducing the specificity of candidate therapeutics. New technologies, and advances in understanding the mechanisms of Wnt signaling, have improved our understanding of the nuances of Wnt signaling and are leading to promising new strategies to target Wnt signaling pathways.

  7. Socioeconomic inequalities in breast cancer incidence and mortality in Europe—a systematic review and meta-analysis

    PubMed Central

    Andersson, Emelie; Ahlberg, Ida; Nilbert, Mef; Gerdtham, Ulf

    2016-01-01

    Background: Breast cancer is the leading cause of female cancer in Europe and is estimated to affect more than one in 10 women. Higher socioeconomic status has been linked to higher incidence but lower case fatality, while the impact on mortality is ambiguous. Methods: We performed a systematic literature review and meta-analysis on studies on association between socioeconomic status and breast cancer outcomes in Europe, with a focus on effects of confounding factors. Summary relative risks (SRRs) were calculated. Results: The systematic review included 25 articles of which 8 studied incidence, 10 case fatality and 8 mortality. The meta-analysis showed a significantly increased incidence (SRR 1.25, 1.17–1.32), a significantly decreased case fatality (SRR 0.72, 0.63–0.81) and a significantly increased mortality (SRR 1.16, 1.10–1.23) for women with higher socioeconomic status. The association for incidence became insignificant when reproductive factors were included. Case fatality remained significant after controlling for tumour characteristics, treatment factors, comorbidity and lifestyle factors. Mortality remained significant after controlling for reproductive factors. Conclusion: Women with higher socioeconomic status show significantly higher breast cancer incidence, which may be explained by reproductive factors, mammography screening, hormone replacement therapy and lifestyle factors. Lower case fatality for women with higher socioeconomic status may be partly explained by differences in tumour characteristics, treatment factors, comorbidity and lifestyle factors. Several factors linked to breast cancer risk and outcome, such as lower screening attendance for women with lower socioeconomic status, are suitable targets for policy intervention aimed at reducing socioeconomic-related inequalities in health outcomes. PMID:27221607

  8. Socio-economic inequality and HIV in South Africa

    PubMed Central

    2013-01-01

    Background The linkage between the socio-economic inequality and HIV outcomes was analysed using data from a population-based household survey that employed multistage-stratified sampling. The goal is to help refocus attention on how HIV is linked to inequalities. Methods A socio-economic index (SEI) score, derived using Multiple Correspondence Analysis of measures of ownership of durable assets, was used to generate three SEI groups: Low (poorest), Middle, and Upper (no so poor). Distribution of HIV outcomes (i.e. HIV prevalence, access to HIV/AIDS information, level of stigma towards HIV/AIDS, perceived HIV risk and sexual behaviour) across the SEI groups, and other background characteristics was assessed using weighted data. Univariate and multivariate logistic regression was used to assess the covariates of the HIV outcomes across the socio-economic groups. The study sample include 14,384 adults 15 years and older. Results More women (57.5%) than men (42.3%) were found in the poor SEI [P<0.001]. HIV prevalence was highest among the poor (20.8%) followed by those in the middle (15.9%) and those in the upper SEI (4.6%) [P<0.001]. It was also highest among women compared to men (19.7% versus 11.4% respectively) and among black Africans (20.2%) compared to other races [P<0.001]. Individuals in the upper SEI reported higher frequency of HIV testing (59.3%) compared to the low SEI (47.7%) [P< 0.001]. Only 20.5% of those in poor SEI had “good access to HIV/AIDS information” compared to 79.5% in the upper SEI (P<0.001). A higher percentage of the poor had a stigmatizing attitude towards HIV/AIDS (45.6%) compared to those in the upper SEI (34.8%) [P< 0.001]. There was a high personal HIV risk perception among the poor (40.0%) and it declined significantly to 10.9% in the upper SEI. Conclusions Our findings underline the disproportionate burden of HIV disease and HIV fear among the poor and vulnerable in South Africa. The poor are further disadvantaged by lack of

  9. Race, Socioeconomic Status, and Age: Exploring Intersections in Preterm Birth Disparities among Teen Mothers

    PubMed Central

    Coley, Sheryl L.; Nichols, Tracy R.; Rulison, Kelly L.; Aronson, Robert E.; Brown-Jeffy, Shelly L.; Morrison, Sharon D.

    2015-01-01

    Few studies have examined disparities in adverse birth outcomes and compared contributing socioeconomic factors specifically between African-American and White teen mothers. This study examined intersections between neighborhood socioeconomic status (as defined by census-tract median household income), maternal age, and racial disparities in preterm birth (PTB) outcomes between African-American and White teen mothers in North Carolina. Using a linked dataset with state birth record data and socioeconomic information from the 2010 US Census, disparities in preterm birth outcomes for 16,472 teen mothers were examined through bivariate and multilevel analyses. African-American teens had significantly greater odds of PTB outcomes than White teens (OR = 1.38, 95% CI 1.21, 1.56). Racial disparities in PTB rates significantly varied by neighborhood income; PTB rates were 2.1 times higher for African-American teens in higher income neighborhoods compared to White teens in similar neighborhoods. Disparities in PTB did not vary significantly between teens younger than age 17 and teens ages 17-19, although the magnitude of racial disparities was larger between younger African-American and White teens. These results justify further investigations using intersectional frameworks to test the effects of racial status, neighborhood socioeconomic factors, and maternal age on birth outcome disparities among infants born to teen mothers. PMID:25729614

  10. Impact of socioeconomic status on municipal solid waste generation rate.

    PubMed

    Khan, D; Kumar, A; Samadder, S R

    2016-03-01

    The solid waste generation rate was expected to vary in different socioeconomic groups due to many environmental and social factors. This paper reports the assessment of solid waste generation based on different socioeconomic parameters like education, occupation, income of the family, number of family members etc. A questionnaire survey was conducted in the study area to identify the different socioeconomic groups that may affect the solid waste generation rate and composition. The average waste generated in the municipality is 0.41 kg/capita/day in which the maximum waste was found to be generated by lower middle socioeconomic group (LMSEG) with average waste generation of 0.46 kg/capita/day. Waste characterization indicated that there was no much difference in the composition of wastes among different socioeconomic groups except ash residue and plastic. Ash residue is found to increase as we move lower down the socioeconomic groups with maximum (31%) in lower socioeconomic group (LSEG). The study area is a coal based city hence application of coal and wood as fuel for cooking in the lower socioeconomic group is the reason for high amount of ash content. Plastic waste is maximum (15%) in higher socioeconomic group (HSEG) and minimum (1%) in LSEG. Food waste is a major component of generated waste in almost every socioeconomic group with maximum (38%) in case of HSEG and minimum (28%) in LSEG. This study provides new insights on the role of various socioeconomic parameters on generation of household wastes. PMID:26831564

  11. Impact of socioeconomic status on municipal solid waste generation rate.

    PubMed

    Khan, D; Kumar, A; Samadder, S R

    2016-03-01

    The solid waste generation rate was expected to vary in different socioeconomic groups due to many environmental and social factors. This paper reports the assessment of solid waste generation based on different socioeconomic parameters like education, occupation, income of the family, number of family members etc. A questionnaire survey was conducted in the study area to identify the different socioeconomic groups that may affect the solid waste generation rate and composition. The average waste generated in the municipality is 0.41 kg/capita/day in which the maximum waste was found to be generated by lower middle socioeconomic group (LMSEG) with average waste generation of 0.46 kg/capita/day. Waste characterization indicated that there was no much difference in the composition of wastes among different socioeconomic groups except ash residue and plastic. Ash residue is found to increase as we move lower down the socioeconomic groups with maximum (31%) in lower socioeconomic group (LSEG). The study area is a coal based city hence application of coal and wood as fuel for cooking in the lower socioeconomic group is the reason for high amount of ash content. Plastic waste is maximum (15%) in higher socioeconomic group (HSEG) and minimum (1%) in LSEG. Food waste is a major component of generated waste in almost every socioeconomic group with maximum (38%) in case of HSEG and minimum (28%) in LSEG. This study provides new insights on the role of various socioeconomic parameters on generation of household wastes.

  12. Jubba Environmental and Socio-economic Studies (JESS). Volume 3. Socio-economic studies. Final report

    SciTech Connect

    Not Available

    1989-01-01

    The Government of the Somali Democratic Republic (GSDR), with the support of the international donor community, is prepared to launch a comprehensive program for the development of Jubba Valley. The keystone of the program is construction of a dam on the Jubba River near Baardheere. Planners have been looking toward construction of the dam, among other things, to increase agricultural output by fostering irrigation development. The objectives of the Socio-economic Baseline Study (SEBS) report are to: present a body of a new information on socio-economic life in Jubba Valley; assess the impact of development efforts on socio-economic life; recommend measures to enhance beneficial impacts and mitigate adverse ones; and propose a program to monitor the progress of those impacts and interventions.

  13. Family and Community Influences on Health and Socioeconomic Status: Sibling Correlations Over the Life Course*

    PubMed Central

    Mazumder, Bhashkar

    2012-01-01

    This paper presents new estimates of sibling correlations in health and socioeconomic outcomes over the life course in the U.S. Sibling correlations provide an omnibus measure of the importance of all family and community influences. I find that sibling correlations in a range of health and socioeconomic outcomes start quite high at birth and remain high over the life course. The sibling correlation in birth weight is estimated to be 0.5. Sibling correlations in test scores during childhood are as high as 0.6. Sibling correlations in adult men’s wages are also around 0.5. Decompositions provide suggestive evidence on which pathways may account for the gradients in health and SES by family background. For example, sibling correlations in cognitive skills and non-cognitive skills during childhood are lower controlling for family income. Similarly, parent education levels can account for a sizable portion of the correlation in adult health status among brothers. PMID:23412989

  14. Dexter energy transfer pathways.

    PubMed

    Skourtis, Spiros S; Liu, Chaoren; Antoniou, Panayiotis; Virshup, Aaron M; Beratan, David N

    2016-07-19

    Energy transfer with an associated spin change of the donor and acceptor, Dexter energy transfer, is critically important in solar energy harvesting assemblies, damage protection schemes of photobiology, and organometallic opto-electronic materials. Dexter transfer between chemically linked donors and acceptors is bridge mediated, presenting an enticing analogy with bridge-mediated electron and hole transfer. However, Dexter coupling pathways must convey both an electron and a hole from donor to acceptor, and this adds considerable richness to the mediation process. We dissect the bridge-mediated Dexter coupling mechanisms and formulate a theory for triplet energy transfer coupling pathways. Virtual donor-acceptor charge-transfer exciton intermediates dominate at shorter distances or higher tunneling energy gaps, whereas virtual intermediates with an electron and a hole both on the bridge (virtual bridge excitons) dominate for longer distances or lower energy gaps. The effects of virtual bridge excitons were neglected in earlier treatments. The two-particle pathway framework developed here shows how Dexter energy-transfer rates depend on donor, bridge, and acceptor energetics, as well as on orbital symmetry and quantum interference among pathways.

  15. Sex-linked dominant

    MedlinePlus

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

  16. Are Worry and Rumination Specific Pathways Linking Neuroticism and Symptoms of Anxiety and Depression in Patients with Generalized Anxiety Disorder, Major Depressive Disorder and Mixed Anxiety-Depressive Disorder?

    PubMed

    Merino, Hipólito; Senra, Carmen; Ferreiro, Fátima

    2016-01-01

    This study examines the relationships between neuroticism (higher-order vulnerability factor), the cognitive styles of worry, brooding and reflection (second-order vulnerability factors) and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD), with Major Depressive Disorder (MDD) and with Mixed Anxiety-Depressive Disorder (MADD). One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection), anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of "specific transdiagnostic" mechanisms.

  17. Are Worry and Rumination Specific Pathways Linking Neuroticism and Symptoms of Anxiety and Depression in Patients with Generalized Anxiety Disorder, Major Depressive Disorder and Mixed Anxiety-Depressive Disorder?

    PubMed Central

    Merino, Hipólito; Ferreiro, Fátima

    2016-01-01

    This study examines the relationships between neuroticism (higher-order vulnerability factor), the cognitive styles of worry, brooding and reflection (second-order vulnerability factors) and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD), with Major Depressive Disorder (MDD) and with Mixed Anxiety-Depressive Disorder (MADD). One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection), anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of "specific transdiagnostic" mechanisms. PMID:27243462

  18. Women's relative immunity to the socio-economic health gradient: artifact or real?

    PubMed Central

    Phillips, Susan P.; Hamberg, Katarina

    2015-01-01

    Background Individual and area socio-economic status (SES) are significant predictors of morbidity and mortality in developed and developing countries. However, the span in health from poorest to richest, that is, the socio-economic gradient, appears steeper for men than women. Objective Our aim is to understand women's apparent immunity to the health harms of the SES gradient. Design Findings from a non-systematic search of Medline for population-based, SES gradient studies reporting results for both men and women and with health outcomes of morbidity, mortality or self-rated health (SRH) were reflectively analyzed. Results The 36 papers reviewed generally showed women to be relatively immune to the SES gradient for all but cardiovascular health outcomes. However, addressing the interconnected nature of socio-economic circumstances, exploring whether some measures of SES had ambiguous meanings for either women or men, including modifiers of SES such as household circumstances, social capital or area gender equity, or using indicators of area SES that were contextual rather than aggregates of individual, compositional measures increased the SES gradient for women. Outcome measures that combined mental and physical health, accounted for gender differences in SRH and adjusted for sex-specific differences in causes of mortality also explained some of the observed amelioration of the SES gradient among women. Conclusions Socio-economic circumstances have a real and sustained impact on individual health. The SES gradient appears stronger for men than for women for all health outcomes other than heart disease. However, some of the observed variability between men and women may be an artifact of biased methodology. Considering webs of causation rather than individual markers of SES along with other sources of gender bias can explain much of women's blunted socio-economic gradient and deepen understanding of the pathways from SES to morbidity and mortality overall. PMID

  19. Sex differences in stroke: a socioeconomic perspective

    PubMed Central

    Delbari, Ahmad; Keyghobadi, Farzane; Momtaz, Yadollah Abolfathi; Keyghobadi, Fariba; Akbari, Reza; Kamranian, Houman; Yazdi, Mohammad Shouride; Tabatabaei, Sayed Shahaboddin; Fereshtehnejad, Seyed-Mohammad

    2016-01-01

    Background A number of studies have explored the issue of sex differences in stroke from biomedical perspective; however, there are still large gaps in the existing knowledge. The purpose of this study was to assess whether the differences in socioeconomic status and living conditions between men and women may explain the part of the sex differences in incidence and outcomes of stroke. Methods All stroke participants aged ≥60 years admitted in Vaseie Hospital in Sabzevar, Iran, from March 21, 2013, until March 20, 2014, were included in this study. Computerized tomography and magnetic resonance imaging were used to confirm stroke. A series of χ2 tests were performed and Statistical Program for Social Sciences, Version 21.0, was used to investigate the potential differences between older men and women in stroke incidence and outcomes. Results A total of 159 incident stroke cases were documented during 1 year. The annual rate of stroke was statistically significantly higher in elderly women than in elderly men (401 vs 357 per 100,000; P<0.001). Female elderly participants had significantly lower socioeconomic status, poorer living conditions, and higher lifetime history of depression, hypertension, and diabetes mellitus than their male counterparts. Conclusion The findings from this study showed that elderly women are more adversely affected by stroke in terms of incidence and outcomes of stroke than elderly men. The most noticeable result is that sex differences in socioeconomic status and living conditions may result in increased incidence of stroke and poorer outcomes in elderly women. Therefore, it is imperative to identify vulnerable elderly women and provide them appropriate treatment and services.

  20. Sex differences in stroke: a socioeconomic perspective

    PubMed Central

    Delbari, Ahmad; Keyghobadi, Farzane; Momtaz, Yadollah Abolfathi; Keyghobadi, Fariba; Akbari, Reza; Kamranian, Houman; Yazdi, Mohammad Shouride; Tabatabaei, Sayed Shahaboddin; Fereshtehnejad, Seyed-Mohammad

    2016-01-01

    Background A number of studies have explored the issue of sex differences in stroke from biomedical perspective; however, there are still large gaps in the existing knowledge. The purpose of this study was to assess whether the differences in socioeconomic status and living conditions between men and women may explain the part of the sex differences in incidence and outcomes of stroke. Methods All stroke participants aged ≥60 years admitted in Vaseie Hospital in Sabzevar, Iran, from March 21, 2013, until March 20, 2014, were included in this study. Computerized tomography and magnetic resonance imaging were used to confirm stroke. A series of χ2 tests were performed and Statistical Program for Social Sciences, Version 21.0, was used to investigate the potential differences between older men and women in stroke incidence and outcomes. Results A total of 159 incident stroke cases were documented during 1 year. The annual rate of stroke was statistically significantly higher in elderly women than in elderly men (401 vs 357 per 100,000; P<0.001). Female elderly participants had significantly lower socioeconomic status, poorer living conditions, and higher lifetime history of depression, hypertension, and diabetes mellitus than their male counterparts. Conclusion The findings from this study showed that elderly women are more adversely affected by stroke in terms of incidence and outcomes of stroke than elderly men. The most noticeable result is that sex differences in socioeconomic status and living conditions may result in increased incidence of stroke and poorer outcomes in elderly women. Therefore, it is imperative to identify vulnerable elderly women and provide them appropriate treatment and services. PMID:27660426

  1. Institutional and socioeconomic aspects of water supply

    NASA Astrophysics Data System (ADS)

    Rauchenschwandtner, H.; Pachel, M.

    2012-04-01

    Institutional and socioeconomic aspects of water supply Within the project CC-WaterS the participating researchers of the Vienna University of Economics and B.A. have been responsible for the analysis of the socioeconomic aspects related to water supply and climate change, the assessment of future water demands in the City of Vienna, as well as an estimation of economic consequences of possible water shortages and possible scope for the introduction of new legal guidelines. The institutional and socioeconomic dimensions of drinking water and sanitation systems are being examined by utilisation of different prognostic scenarios in order to assess future costs of water provisioning and future demands of main water users, thus providing an information basis and recommendations for policy and decision makers in the water sector. These dimensions, for example, include EU legislation - especially the Water Framework Directive -, national legislations and strategies targeted at achieving sustainability in water usage, best practices and different forms of regulating water markets, and an analysis of the implications of demographic change. As a basis this task encompasses research of given institutional, social, and legal-political structures in the area of water supply. In this course we provide an analysis of the structural characteristics of water markets, the role of water prices, the increasing perception of water as an economic good as well as implications thereof, the public awareness in regard to climate change and water resources, as well as related legal aspects and involved actors from regional to international level; and show how water resources and the different systems of water provisioning are affected by (ideological) conflicts on various levels. Furthermore, and in order to provide a solid basis for management recommendations related to climate change and water supply, an analytical risk-assessment framework based on the concepts of new institutional

  2. Socioeconomic status and health of immigrants.

    PubMed

    Vacková, Jitka; Brabcová, Iva

    2015-01-01

    The aim of this article is to acquaint the general public with select socioeconomic status (SES) parameters (type of work, education level, employment category, and net monthly income) of select nationalities (Ukrainians, Slovaks, Vietnamese, Poles, and Russians) from a total of 1,014 immigrants residing in the Czech Republic. It will also present a subjective assessment of socioeconomic status and its interconnection with subjective assessment of health status. This work was carried out as part of the "Social determinants and their impact on the health of immigrants living in the Czech Republic" project (identification number LD 13044), which was conducted under the auspices of the European Cooperation in Science and Technology (COST) agency. Quantitative methodology in the form of a questionnaire was selected to facilitate the research aim. Data was processed using the Statistical Package for Social Sciences (SPSS), version 16.0 (SPSS, Inc., Chicago, IL, USA). Statistical analyses were performed using the Pearson chi-square test, adjusted residual analysis, and multivariate correspondence analysis. The results of these tests demonstrated a statistically significant relationship between subjective assessments of socioeconomic status and the following related select characteristics: type of work performed (manual/intellectual), employment categories, education, and net monthly income. Results indicate that those situated lowest on the socioeconomic ladder feel the poorest in terms of health; not only from a subjective perspective, but also in terms of objective parameter comparisons (e.g. manual laborers who earn low wages). As the level of subjective SES assessment increases, the level of subjective health assessment increases, as well. Thus, the relationship has a natural gradient, as was described by Wilkinson and Marmot in 2003. Our study found no evidence of a healthy immigrant effect. Therefore, it was not possible to confirm that health status deteriorates

  3. Socioeconomic status and the developing brain.

    PubMed

    Hackman, Daniel A; Farah, Martha J

    2009-02-01

    Childhood socioeconomic status (SES) is associated with cognitive achievement throughout life. How does SES relate to brain development, and what are the mechanisms by which SES might exert its influence? We review studies in which behavioral, electrophysiological and neuroimaging methods have been used to characterize SES disparities in neurocognitive function. These studies indicate that SES is an important predictor of neurocognitive performance, particularly of language and executive function, and that SES differences are found in neural processing even when performance levels are equal. Implications for basic cognitive neuroscience and for understanding and ameliorating the problems related to childhood poverty are discussed. PMID:19135405

  4. Independent associations of childhood and current socioeconomic status with risk of self-reported doctor-diagnosed arthritis in a family-medicine cohort of North-Carolinians

    PubMed Central

    2013-01-01

    Background Associations of socioeconomic status (SES) with the prevalence of various forms of arthritis are well documented. Increasing evidence suggests that SES during childhood is a lasting determinant of health, but its association with the onset of arthritis remains unclear. Methods Cross-sectional data on 1276 participants originated from 22 family practices in North-Carolina, USA. We created 4-level (high, medium, low, lowest) current SES and childhood SES summary scores based on parental and participant education, occupation and homeownership. We investigated associations of individual SES characteristics, summary scores and SES trajectories (e.g. high/low) with self-reported arthritis in logistic regression models progressively adjusted for race and gender, age, then BMI, and clustered by family practice. Results We found evidence for independent associations of both childhood and current SES with the reporting of arthritis across our models. In covariate-adjusted models simultaneously including current and childhood SES, compared with high SES participants in the lowest childhood SES category (OR = 1.39 [95% CI = 1.04, 1.85]) and those in the low (OR = 1.66 [95% CI = 1.14, 2.42]) and lowest (OR = 2.08 [95% CI = 1.16, 3.74]) categories of current SES had significantly greater odds of having self-reported arthritis. Conclusions Current SES and childhood SES are both associated with the odds of reporting arthritis within this primary-care population, although the possibly superseding influence of existing circumstances must be noted. BMI was a likely mechanism in the association of childhood SES with arthritis onset, and research is needed to elucidate further pathways linking the socioeconomic environment across life-stages and the development of rheumatic diseases. PMID:24256740

  5. Segregation and cardiovascular illness: the role of individual and metropolitan socioeconomic status.

    PubMed

    Jones, Antwan

    2013-07-01

    Demographic and epidemiologic research suggest that cardiovascular illness is negatively linked to socioeconomic status and positively related to racial residential segregation. Relying on 2005 data from the Behavior Risk Factor Surveillance Survey and the American Community Survey, this study examines how segregation and SES (individual and metropolitan) impact hypertension for a sample of 200,102 individuals. Multilevel analyses indicate that both segregation and hypersegregation are associated with hypertension, net of individual and spatial SES. While individual and metropolitan SES have independent effects on hypertension, these effects also differ across segregation type. In segregated and hypersegregated environments, highly educated and high-earning individuals seem to be protected against hypertension. In extremely hypersegregated areas, areas where there is very little interaction with non-black residents, SES does not have any protective benefit. These findings reveal that SES has differential effects across segregation types and that hypertension in disadvantaged (extremely hypersegregated) areas may be a function of structural constraints rather than socioeconomic position.

  6. Analysing the socioeconomic determinants of hypertension in South Africa: a structural equation modelling approach

    PubMed Central

    2014-01-01

    Background Epidemiological research has long observed a varying prevalence of hypertension across socioeconomic strata. However, patterns of association and underlying causal mechanisms are poorly understood in sub-Saharan Africa. Using education and income as indicators, we investigated the extent to which socioeconomic status is linked to blood pressure in the first wave of the National Income Dynamics Study — a South African longitudinal study of more than 15000 adults – and whether bio-behavioural risk factors mediate the association. Methods In a cross-sectional analysis, structural equation modelling was employed to estimate the effect of socioeconomic status on systolic and diastolic blood pressure and to assess the role of a set of bio-behavioural risk factors in explaining the observed relationships. Results After adjustment for age, race and antihypertensive treatment, higher education and income were independently associated with higher diastolic blood pressure in men. In women higher education predicted lower values of both diastolic and systolic blood pressure while higher income predicted lower systolic blood pressure. In both genders, body mass index was a strong mediator of an adverse indirect effect of socioeconomic status on blood pressure. Together with physical exercise, alcohol use, smoking and resting heart rate, body mass index therefore contributed substantially to mediation of the observed relationships in men. By contrast, in women unmeasured factors played a greater role. Conclusion In countries undergoing epidemiological transition, effects of socioeconomic status on blood pressure may vary by gender. In women, factors other than those listed above may have substantial role in mediating the association and merit investigation. PMID:24885860

  7. Socioeconomic aspects of the circumstances and consequences of car crashes among young adults.

    PubMed

    Hasselberg, Marie; Vaez, Marjan; Laflamme, Lucie

    2005-01-01

    The study examines whether there are socioeconomic differences between young adult car drivers involved in road-traffic crashes with regard to crash-injury severity and crash circumstances. Differences in social patterning based on socioeconomic position (SEP) of origin and of destination, and also the effect of gender, are considered. Subjects born in 1970-1972 were extracted from the Swedish Population and Housing Census of 1985 (n = 329,716). Individual records from the 1985 census were linked to road-traffic data for the period 1988-2000 on the basis of a search for each subject's first police-registered road-traffic crash as a car driver (n = 12,502). Information on household socioeconomic group was taken from the census of 1985, and data on completed education at age 28-30 were gathered from Sweden's Register of Education. Two categories of crash severity were analysed (minor/no injury and severe/fatal injury), and also five crash circumstances (based on a classification of five crash descriptors). Both crash severity and crash circumstances are unequally distributed across social groups among young adult drivers. Social patterning is more pronounced for severe injuries/fatalities, and is consistently so across crash circumstances depending on SEP of destination, particularly for males. Socioeconomic differences are more pronounced for crash circumstances characterised as front-on and overtaking collisions and for single-vehicle crashes (43% of total crashes). In conclusion,the excess risk of young drivers from lower socioeconomic groups is consistent over crash severity but more pronounced as severity increases and for certain crash circumstances. PMID:15587501

  8. Early-life course socioeconomic factors and chronic kidney disease.

    PubMed

    Brophy, Patrick D; Shoham, David A; Charlton, Jennifer R; Carmody, J Bryan; Reidy, Kimberly J; Harshman, Lyndsay; Segar, Jeffrey; Askenazi, David

    2015-01-01

    Kidney failure or ESRD affects approximately 650,000 Americans, whereas the number with earlier stages of CKD is much higher. Although CKD and ESRD are usually associated with adulthood, it is likely that the initial stages of CKD begin early in life. Many of these pathways are associated with low birth weight and disadvantaged socioeconomic status (SES) in childhood, translating childhood risk into later-life CKD and kidney failure. Social factors are thought to be fundamental causes of disease. Although the relationship between adult SES and CKD has been well established, the role of early childhood SES for CKD risk remains obscure. This review provides a rationale for examining the association between early-life SES and CKD. By collecting data on early-life SES and CKD, the interaction with other periods in the life course could also be studied, allowing for examination of whether SES trajectories (eg, poverty followed by affluence) or cumulative burden (eg, poverty at multiple time points) are more relevant to lifetime CKD risk.

  9. Socioeconomic differences in obesity among Mexican adolescents

    PubMed Central

    ULLMANN, S. HEIDI; BUTTENHEIM, ALISON M.; GOLDMAN, NOREEN; PEBLEY, ANNE R.; WONG, REBECA

    2012-01-01

    Objective We investigate socioeconomic disparities in adolescent obesity in Mexico. Three questions are addressed. First, what is the social patterning of obesity among Mexican adolescents? Second, what are the separate and joint associations of maternal and paternal education with adolescent obesity net of household wealth? Third, are there differences in socioeconomic status (SES) gradients among Mexican boys and girls, rural residents and non-rural residents? Methods Using data from the Mexican National Health Survey 2000 we examined the slope and direction of the association between SES and adolescent obesity. We also estimated models for sub-populations to examine differences in the social gradients in obesity by sex and non-rural residence. Results We find that household economic status (asset ownership and housing quality) is positively associated with adolescent obesity. High paternal education is related to lower obesity risk, whereas the association between maternal education and obesity is positive, but not always significant. Conclusion The household wealth components of SES appear to predispose Mexican adolescents to higher obesity risk. The effects of parental education are more complex. These findings have important policy implications in Mexico and the United States. PMID:20883181

  10. Malocclusion and socioeconomic indicators in primary dentition.

    PubMed

    Sousa, Raulison Vieira de; Pinto-Monteiro, Ana Karla de Almeida; Martins, Carolina Castro; Granville-Garcia, Ana Flávia; Paiva, Saul Martins

    2014-01-01

    The aim of the present study was to determine the prevalence of malocclusion and associations with socioeconomic indicators among preschoolers. A cross-sectional study was conducted with 732 children 3 to 5 years of age in the city of Campina Grande, Brazil. Three dentists underwent a calibration exercise (K = 0.85–0.90) and diagnosed malocclusion based on the criteria proposed by Foster & Hamilton and Grabowski et al. Parents/guardians answered a questionnaire addressing sociodemographic aspects. Data analysis involved descriptive statistics and bivariate Poisson regression (PR; α = 5%). The prevalence of malocclusion was 62.4%. The most frequent types were increased overjet (42.6%), anterior open bite (21%) and deep overbite (19.3%). An association was found between malocclusion and age: the prevalence of malocclusion was greater among younger children, with the highest prevalence among 3-year-olds (PR = 1.116; 95%CI = 1.049–1.187). The prevalence of malocclusion was high. Mother's schooling and household income were not associated with malocclusion. Socioeconomic factors were also not associated with the occurrence of malocclusion.

  11. Socioeconomic status and smoking: a review.

    PubMed

    Hiscock, Rosemary; Bauld, Linda; Amos, Amanda; Fidler, Jennifer A; Munafò, Marcus

    2012-02-01

    Smoking prevalence is higher among disadvantaged groups, and disadvantaged smokers may face higher exposure to tobacco's harms. Uptake may also be higher among those with low socioeconomic status (SES), and quit attempts are less likely to be successful. Studies have suggested that this may be the result of reduced social support for quitting, low motivation to quit, stronger addiction to tobacco, increased likelihood of not completing courses of pharmacotherapy or behavioral support sessions, psychological differences such as lack of self-efficacy, and tobacco industry marketing. Evidence of interventions that work among lower socioeconomic groups is sparse. Raising the price of tobacco products appears to be the tobacco control intervention with the most potential to reduce health inequalities from tobacco. Targeted cessation programs and mass media interventions can also contribute to reducing inequalities. To tackle the high prevalence of smoking among disadvantaged groups, a combination of tobacco control measures is required, and these should be delivered in conjunction with wider attempts to address inequalities in health. PMID:22092035

  12. Dynamic motifs in socio-economic networks

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Shao, Shuai; Stanley, H. Eugene; Havlin, Shlomo

    2014-12-01

    Socio-economic networks are of central importance in economic life. We develop a method of identifying and studying motifs in socio-economic networks by focusing on “dynamic motifs,” i.e., evolutionary connection patterns that, because of “node acquaintances” in the network, occur much more frequently than random patterns. We examine two evolving bi-partite networks: i) the world-wide commercial ship chartering market and ii) the ship build-to-order market. We find similar dynamic motifs in both bipartite networks, even though they describe different economic activities. We also find that “influence” and “persistence” are strong factors in the interaction behavior of organizations. When two companies are doing business with the same customer, it is highly probable that another customer who currently only has business relationship with one of these two companies, will become customer of the second in the future. This is the effect of influence. Persistence means that companies with close business ties to customers tend to maintain their relationships over a long period of time.

  13. Identification and expression analysis of immune-related genes linked to Rel/NF-κB signaling pathway under stresses and bacterial challenge from the small abalone Haliotis diversicolor.

    PubMed

    Zhang, Xin; Huang, Yitao; Cai, Xiuhong; Zou, Zhihua; Wang, Guodong; Wang, Shuhong; Wang, Yilei; Zhang, Ziping

    2014-12-01

    Inhibitor of NF-κB (IκB), nuclear factor-κB (NF-κB), and Akirin2 are all important members of Rel/NF-κB signaling pathway, which plays a pivotal role in regulating the innate immune response of vertebrates and invertebrates. In this study, the IκB (SaIκB) and Akirin2 (SaAkirin2) cDNAs of small abalone Haliotis diversicolor were cloned and characterized. The full length cDNA of SaIκB and SaAkirin2 were 1748 bp and 1452 bp respectively, encoding a protein of 401 aa and 187 aa respectively. A conserved degradation motif (DS56GIYS60) and six ankyrin repeats were identified in the SaIκB by SMART analysis. Meanwhile, a typical nuclear localization signal (NLS) was found at the N-terminal region of the SaAkirin2 protein. Also, the mRNA expression level of SaIκB, SaAkirin2, and AbNF-κB were detected by quantitative real-time PCR. The results revealed that all these three genes were ubiquitously expressed in 7 selected tissues. The expression level of SaIκB in gills was higher than that in other tissues (P < 0.05) while the expression level of AbNF-κB was significantly higher in hepatopancreas and haemocytes. The highest expression level of SaAkirin2 was detected in hepatopancreas, followed by mantle. The mRNA expression levels in either gills or haemocytes of SaIκB, SaAkirin2, and AbNF-κB were significantly up-regulated (P < 0.05) post thermal stress, hypoxia exposure, thermal plus hypoxia stress and the injection of Vibrio parahaemolyticus. These results indicated that these three NF-κB signaling pathway-related genes are involved in response to bacterial infection and play essential roles in response to thermal and hypoxia stress. PMID:25158315

  14. Autocrine Tumor Necrosis Factor Alpha Links Endoplasmic Reticulum Stress to the Membrane Death Receptor Pathway through IRE1α-Mediated NF-κB Activation and Down-Regulation of TRAF2 Expression

    PubMed Central

    Hu, Ping; Han, Zhang; Couvillon, Anthony D.; Kaufman, Randal J.; Exton, John H.

    2006-01-01

    NF-κB is critical for determining cellular sensitivity to apoptotic stimuli by regulating both mitochondrial and death receptor apoptotic pathways. The endoplasmic reticulum (ER) emerges as a new apoptotic signaling initiator. However, the mechanism by which ER stress activates NF-κB and its role in regulation of ER stress-induced cell death are largely unclear. Here, we report that, in response to ER stress, IKK forms a complex with IRE1α through the adapter protein TRAF2. ER stress-induced NF-κB activation is impaired in IRE1α knockdown cells and IRE1α−/− MEFs. We found, however, that inhibiting NF-κB significantly decreased ER stress-induced cell death in a caspase-8-dependent manner. Gene expression analysis revealed that ER stress-induced expression of tumor necrosis factor alpha (TNF-α) was IRE1α and NF-κB dependent. Blocking TNF receptor 1 signaling significantly inhibited ER stress-induced cell death. Further studies suggest that ER stress induces down-regulation of TRAF2 expression, which impairs TNF-α-induced activation of NF-κB and c-Jun N-terminal kinase and turns TNF-α from a weak to a powerful apoptosis inducer. Thus, ER stress induces two signals, namely TNF-α induction and TRAF2 down-regulation. They work in concert to amplify ER-initiated apoptotic signaling through the membrane death receptor. PMID:16581782

  15. Reelin, an extracellular matrix protein linked to early onset psychiatric diseases, drives postnatal development of the prefrontal cortex via GluN2B-NMDARs and the mTOR pathway.

    PubMed

    Iafrati, J; Orejarena, M J; Lassalle, O; Bouamrane, L; Gonzalez-Campo, C; Chavis, P

    2014-04-01

    Defective brain extracellular matrix (ECM) is a factor of vulnerability in various psychiatric diseases such as schizophrenia, depression and autism. The glycoprotein reelin is an essential building block of the brain ECM that modulates neuronal development and participates to the functions of adult central synapses. The reelin gene (RELN) is a strong candidate in psychiatric diseases of early onset, but its synaptic and behavioral functions in juvenile brain circuits remain unresolved. Here, we found that in juvenile reelin-haploinsufficient heterozygous reeler mice (HRM), abnormal fear memory erasure is concomitant to reduced dendritic spine density and anomalous long-term potentiation in the prefrontal cortex. In juvenile HRM, a single in vivo injection with ketamine or Ro25-6981 to inhibit GluN2B-N-methyl-D-aspartate receptors (NMDARs) restored normal spine density, synaptic plasticity and converted fear memory to an erasure-resilient state typical of adult rodents. The functional and behavioral rescue by ketamine was prevented by rapamycin, an inhibitor of the mammalian target of rapamycin pathway. Finally, we show that fear memory erasure persists until adolescence in HRM and that a single exposure to ketamine during the juvenile period reinstates normal fear memory in adolescent mice. Our results show that reelin is essential for successful structural, functional and behavioral development of juvenile prefrontal circuits and that this developmental period provides a critical window for therapeutic rehabilitation with GluN2B-NMDAR antagonists.

  16. Women's Work Pathways Across the Life Course.

    PubMed

    Damaske, Sarah; Frech, Adrianne

    2016-04-01

    Despite numerous changes in women's employment in the latter half of the twentieth century, women's employment continues to be uneven and stalled. Drawing from data on women's weekly work hours in the National Longitudinal Survey of Youth (NLSY79), we identify significant inequality in women's labor force experiences across adulthood. We find two pathways of stable full-time work for women, three pathways of part-time employment, and a pathway of unpaid labor. A majority of women follow one of the two full-time work pathways, while fewer than 10% follow a pathway of unpaid labor. Our findings provide evidence of the lasting influence of work-family conflict and early socioeconomic advantages and disadvantages on women's work pathways. Indeed, race, poverty, educational attainment, and early family characteristics significantly shaped women's work careers. Work-family opportunities and constraints also were related to women's work hours, as were a woman's gendered beliefs and expectations. We conclude that women's employment pathways are a product of both their resources and changing social environment as well as individual agency. Significantly, we point to social stratification, gender ideologies, and work-family constraints, all working in concert, as key explanations for how women are "tracked" onto work pathways from an early age. PMID:27001314

  17. Race/ethnicity and socioeconomic status: measurement and methodological issues.

    PubMed

    Williams, D R

    1996-01-01

    This article considers the ways in which race/ethnicity and socioeconomic status (SES) relate to each other and combine to affect racial variations in health status. The author reviews a number of methodological issues concerning the assessment of race in the United States that importantly affect the quality of the available data on racial differences in health. These issues include the discrepancy between self-identification and observer-reported race, changing racial classification categories and racial identification, the difficulties in categorizing persons of mixed racial parentage, and census undercount. In discussing the complex interactions between race and SES, the author first describes the relationship between race and SES and assesses the role of SES in accounting for racial differences in health, then shows how the failure of SES to completely account for racial variations in health status emphasizes the need for health researchers to give more systematic attention to the unique factors linked to race that affect health. These factors include racism, migration, acculturation, and the comprehensive assessment of SES.

  18. The influence of socioeconomic status on children's brain structure.

    PubMed

    Jednoróg, Katarzyna; Altarelli, Irene; Monzalvo, Karla; Fluss, Joel; Dubois, Jessica; Billard, Catherine; Dehaene-Lambertz, Ghislaine; Ramus, Franck

    2012-01-01

    Children's cognitive abilities and school achievements are deeply affected by parental socioeconomic status (SES). Numerous studies have reported lower cognitive performance in relation to unfavorable environments, but little is known about the effects of SES on the child's neural structures. Here, we systematically explore the association between SES and brain anatomy through MRI in a group of 23 healthy 10-year-old children with a wide range of parental SES. We confirm behaviorally that language is one of the cognitive domains most affected by SES. Furthermore, we observe widespread modifications in children's brain structure. A lower SES is associated with smaller volumes of gray matter in bilateral hippocampi, middle temporal gyri, left fusiform and right inferior occipito-temporal gyri, according to both volume- and surface-based morphometry. Moreover, we identify local gyrification effects in anterior frontal regions, supportive of a potential developmental lag in lower SES children. In contrast, we found no significant association between SES and white matter architecture. These findings point to the potential neural mediators of the link between unfavourable environmental conditions and cognitive skills.

  19. Socioeconomic profiles of native American communities: Duckwater Shoshone Reservation

    SciTech Connect

    Hamby, M.

    1991-10-01

    This report presents socioeconomic aspects of Native Americans of the Duckwater Shoshone Reservation. A survey is included concerning their views on the proposed Yucca Mountain waste repository. (CBS)

  20. Socioeconomic inequalities in youth smoking in Brazil

    PubMed Central

    Barreto, Sandhi Maria; de Figueiredo, Roberta Carvalho; Giatti, Luana

    2013-01-01

    Objective The contribution of smoking to socioeconomic inequalities in health is increasing worldwide, including in Brazil. Youth smoking may play an important role in the increasing social inequalities related to smoking. This study investigates social determinants of smoking among 15-year-old to 19-year-old individuals. Design Cross-sectional study. Setting The study uses data of 3536 participants aged 15–19 years of age of the Global Adult Tobacco Survey (GATS) and the National Household Sample Survey (Pesquisa Nacional por Amostragem de Domicilio, PNAD) obtained from household interviews. Smoking was defined as currently smoking tobacco products, regardless of frequency. Household socioeconomic indicators included per capita income, the educational level and sex of the head of the household, the presence of smoking restrictions and the number of smokers (excluding adolescents). Adolescent social factors included years of delaying school and social status (full-time student, working, and neither working nor studying). The hierarchical logistic regression analysis considered the effect of the complex sampling design. Results From 3536 participants, 6.2% were smokers (95% CI 5.4 to 7.1). More men than women had the habit of smoking (7.2%; 5.9 to 8.6 vs 3.6%; 2.7 to 4.6). The likelihood of smoking was significantly greater for men and older teens. There was an upward trend in the OR of smoking according to the number of smokers in the house. Adolescents living in households with no smoking restrictions had a greater likelihood of being smokers. OR of smoking rose as the number of years of delaying school increased, being about three times greater among adolescents who were working and five times greater among those who were neither studying nor working. Conclusions Results demonstrate that socioeconomic inequality in smoking is established at younger ages and that school delay as well as school abandonment may contribute to increased smoking

  1. Allelic Variants in Arhgef11 via the Rho-Rock Pathway Are Linked to Epithelial-Mesenchymal Transition and Contributes to Kidney Injury in the Dahl Salt-Sensitive Rat.

    PubMed

    Jia, Zhen; Johnson, Ashley C; Wang, Xuexiang; Guo, Zibiao; Dreisbach, Albert W; Lewin, Jack R; Kyle, Patrick B; Garrett, Michael R

    2015-01-01

    Previously, genetic analyses identified that variants in Arhgef11 may influence kidney injury in the Dahl salt-sensitive (S) rat, a model of hypertensive chronic kidney disease. To understand the potential mechanism by which altered expression and/or protein differences in Arhgef11 could play a role in kidney injury, stably transduced Arhgef11 knockdown cell lines as well as primary cultures of proximal tubule cells were studied. Genetic knockdown of Arhgef11 in HEK293 and NRK resulted in reduced RhoA activity, decreased activation of Rho-ROCK pathway, and less stress fiber formation versus control, similar to what was observed by pharmacological inhibition (fasudil). Primary proximal tubule cells (PTC) cultured from the S exhibited increased expression of Arhgef11, increased RhoA activity, and up regulation of Rho-ROCK signaling compared to control (small congenic). The cells were also more prone (versus control) to TGFβ-1 induced epithelial-mesenchymal transition (EMT), a hallmark feature of the development of renal interstitial fibrosis, and characterized by development of spindle shape morphology, gene expression changes in EMT markers (Col1a3, Mmp9, Bmp7, and Ocln) and increased expression of N-Cadherin and Vimentin. S derived PTC demonstrated a decreased ability to uptake FITC-albumin compared to the small congenic in vitro, which was confirmed by assessment of albumin re-uptake in vivo by infusion of FITC-albumin and immunofluorescence imaging. In summary, these studies suggest that genetic variants in the S form of Arhgef11 via increased expression and/or protein activity play a role in promoting kidney injury in the S rat through changes in cell morphology (Rho-Rock and/or EMT) that impact the function of tubule cells.

  2. Allelic Variants in Arhgef11 via the Rho-Rock Pathway Are Linked to Epithelial–Mesenchymal Transition and Contributes to Kidney Injury in the Dahl Salt-Sensitive Rat

    PubMed Central

    Jia, Zhen; Johnson, Ashley C.; Wang, Xuexiang; Guo, Zibiao; Dreisbach, Albert W.; Lewin, Jack R.; Kyle, Patrick B.; Garrett, Michael R.

    2015-01-01

    Previously, genetic analyses identified that variants in Arhgef11 may influence kidney injury in the Dahl salt-sensitive (S) rat, a model of hypertensive chronic kidney disease. To understand the potential mechanism by which altered expression and/or protein differences in Arhgef11 could play a role in kidney injury, stably transduced Arhgef11 knockdown cell lines as well as primary cultures of proximal tubule cells were studied. Genetic knockdown of Arhgef11 in HEK293 and NRK resulted in reduced RhoA activity, decreased activation of Rho-ROCK pathway, and less stress fiber formation versus control, similar to what was observed by pharmacological inhibition (fasudil). Primary proximal tubule cells (PTC) cultured from the S exhibited increased expression of Arhgef11, increased RhoA activity, and up regulation of Rho-ROCK signaling compared to control (small congenic). The cells were also more prone (versus control) to TGFβ-1 induced epithelial-mesenchymal transition (EMT), a hallmark feature of the development of renal interstitial fibrosis, and characterized by development of spindle shape morphology, gene expression changes in EMT markers (Col1a3, Mmp9, Bmp7, and Ocln) and increased expression of N-Cadherin and Vimentin. S derived PTC demonstrated a decreased ability to uptake FITC-albumin compared to the small congenic in vitro, which was confirmed by assessment of albumin re-uptake in vivo by infusion of FITC-albumin and immunofluorescence imaging. In summary, these studies suggest that genetic variants in the S form of Arhgef11 via increased expression and/or protein activity play a role in promoting kidney injury in the S rat through changes in cell morphology (Rho-Rock and/or EMT) that impact the function of tubule cells. PMID:26172442

  3. The modifying effect of socioeconomic status on the relationship between traffic, air pollution and respiratory health in elementary schoolchildren.

    PubMed

    Cakmak, Sabit; Hebbern, Christopher; Cakmak, Jasmine D; Vanos, Jennifer

    2016-07-15

    The volume and type of traffic and exposure to air pollution have been found to be associated with respiratory health, but few studies have considered the interaction with socioeconomic status at the household level. We investigated the relationships of respiratory health related to traffic type, traffic volume, and air pollution, stratifying by socioeconomic status, based on household income and education, in 3591 schoolchildren in Windsor, Canada. Interquartile range changes in traffic exposure and pollutant levels were linked to respiratory symptoms and objective measures of lung function using generalised linear models for three levels of income and education. In 95% of the relationships among all cases, the odds ratios for reported respiratory symptoms (a decrease in measured lung function), based on an interquartile range change in traffic exposure or pollutant, were greater in the lower income/education groups than the higher, although the odds ratios were in most cases not significant. However, in up to 62% of the cases, the differences between high and low socioeconomic groups were statistically significant, thus indicating socioeconomic status (SES) as a significant effect modifier. Our findings indicate that children from lower socioeconomic households have a higher risk of specific respiratory health problems (chest congestion, wheezing) due to traffic volume and air pollution exposure.

  4. The modifying effect of socioeconomic status on the relationship between traffic, air pollution and respiratory health in elementary schoolchildren.

    PubMed

    Cakmak, Sabit; Hebbern, Christopher; Cakmak, Jasmine D; Vanos, Jennifer

    2016-07-15

    The volume and type of traffic and exposure to air pollution have been found to be associated with respiratory health, but few studies have considered the interaction with socioeconomic status at the household level. We investigated the relationships of respiratory health related to traffic type, traffic volume, and air pollution, stratifying by socioeconomic status, based on household income and education, in 3591 schoolchildren in Windsor, Canada. Interquartile range changes in traffic exposure and pollutant levels were linked to respiratory symptoms and objective measures of lung function using generalised linear models for three levels of income and education. In 95% of the relationships among all cases, the odds ratios for reported respiratory symptoms (a decrease in measured lung function), based on an interquartile range change in traffic exposure or pollutant, were greater in the lower income/education groups than the higher, although the odds ratios were in most cases not significant. However, in up to 62% of the cases, the differences between high and low socioeconomic groups were statistically significant, thus indicating socioeconomic status (SES) as a significant effect modifier. Our findings indicate that children from lower socioeconomic households have a higher risk of specific respiratory health problems (chest congestion, wheezing) due to traffic volume and air pollution exposure. PMID:27064731

  5. Physiology of central pathways.

    PubMed

    Cullen, K E

    2016-01-01

    The relative simplicity of the neural circuits that mediate vestibular reflexes is well suited for linking systems and cellular levels of analyses. Notably, a distinctive feature of the vestibular system is that neurons at the first central stage of sensory processing in the vestibular nuclei are premotor neurons; the same neurons that receive vestibular-nerve input also send direct projections to motor pathways. For example, the simplicity of the three-neuron pathway that mediates the vestibulo-ocular reflex leads to the generation of compensatory eye movements within ~5ms of a head movement. Similarly, relatively direct pathways between the labyrinth and spinal cord control vestibulospinal reflexes. A second distinctive feature of the vestibular system is that the first stage of central processing is strongly multimodal. This is because the vestibular nuclei receive inputs from a wide range of cortical, cerebellar, and other brainstem structures in addition to direct inputs from the vestibular nerve. Recent studies in alert animals have established how extravestibular signals shape these "simple" reflexes to meet the needs of current behavioral goal. Moreover, multimodal interactions at higher levels, such as the vestibular cerebellum, thalamus, and cortex, play a vital role in ensuring accurate self-motion and spatial orientation perception. PMID:27638060

  6. THOC5, a member of the mRNA export complex: a novel link between mRNA export machinery and signal transduction pathways in cell proliferation and differentiation

    PubMed Central

    2014-01-01

    Cell growth, differentiation, and commitment to a restricted lineage are guided by a timely expressed set of growth factor/cytokine receptors and their down-stream transcription factor genes. Transcriptional control mechanisms of gene expression during differentiation have been mainly studied by focusing on the cis- and trans-elements in promoters however, the role of mRNA export machinery during differentiation has not been adequately examined. THO (Suppressors of the transcriptional defects of hpr1 delta by overexpression) complex 5 (THOC5) is a member of THO complex which is a subcomplex of the transcription/export complex (TREX). THOC5 is evolutionarily conserved in higher eukaryotes, however the exact roles of THOC5 in transcription and mRNA export are still unclear. In this review, we focus on recently uncovered aspects of the role of THOC5 in signal transduction induced by extracellular stimuli. THOC5 is phosphorylated by several protein kinases at multiple residues upon extracellular stimuli. These include stimulation with growth factors/cytokines/chemokines, or DNA damage reagents. Furthermore, THOC5 is a substrate for several oncogenic tyrosine kinases, suggesting that THOC5 may be involved in cancer development. Recent THOC5 knockout mouse data reveal that THOC5 is an essential element in the maintenance of stem cells and growth factor/cytokine-mediated differentiation/proliferation. Furthermore, depletion of THOC5 influences less than 1% of total mRNA export in the steady state, however it influences more than 90% of growth factor/cytokine induced genes. THOC5, thereby contributes to the 3′ processing and/or export of immediate-early genes induced by extracellular stimuli. These studies bring new insight into the link between the mRNA export complex and immediate-early gene response. The data from these studies also suggest that THOC5 may be a useful tool for studying stem cell biology, for modifying the differentiation processes and for cancer

  7. Phosphorylation of bacterial-type phosphoenolpyruvate carboxylase by a Ca2+-dependent protein kinase suggests a link between Ca2+ signalling and anaplerotic pathway control in developing castor oil seeds.

    PubMed

    Hill, Allyson T; Ying, Sheng; Plaxton, William C

    2014-02-15

    The aim of the present study was to characterize the native protein kinase [BTPC (bacterial-type phosphoenolpyruvate carboxylase)-K (BTPC Ser451 kinase)] that in vivo phosphorylates Ser451 of the BTPC subunits of an unusual Class-2 PEP (phosphoenolpyruvate) carboxylase hetero-octameric complex of developing COS (castor oil seeds). COS BTPC-K was highly purified by PEG fractionation and hydrophobic size-exclusion anion-exchange and affinity chromatographies. BTPC-K phosphorylated BTPC strictly at Ser451 (Km=1.0 μM; pH optimum=7.3), a conserved target residue occurring within an intrinsically disordered region, as well as the protein histone III-S (Km=1.7 μM), but not a COS plant-type PEP carboxylase or sucrose synthase or α-casein. Its activity was Ca2+- (K0.5=2.7 μM) and ATP- (Km=6.6 μM) dependent, and markedly inhibited by trifluoperazine, 3-phosphoglycerate and PEP, but insensitive to calmodulin or 14-3-3 proteins. BTPC-K exhibited a native molecular mass of ~63 kDa and was soluble rather than membrane-bound. Inactivation and reactivation occurred upon BTPC-K's incubation with GSSG and then DTT respectively. Ser451 phosphorylation by BTPC-K inhibited BTPC activity by ~50% when assayed under suboptimal conditions (pH 7.3, 1 mM PEP and 10 mM L-malate). Our collective results indicate a possible link between cytosolic Ca2+ signalling and anaplerotic flux control in developing COS.

  8. Socioeconomic factors and prevalence of endemic goitre.

    PubMed

    Joshi, D C; Mishra, V N; Bhatnagar, M; Singh, R B; Garg, S K; Chopra, H

    1993-01-01

    The present study was conducted on 2611 school children of a rural area of Meerut, with the objectives to find out the prevalence and distribution of endemic goitre and the socioeconomic variables associated with the distribution of the endemic goitre. Grading of goitre was done as per the criteria laid down by the WHO-1979 (1). The overall prevalence rate of endemic goitre was 50.1%, the prevalence was more among females (55.1%) as compared to males (47.2%). Maximum number of goitre cases were having grade Ia enlargement (46.9%) followed by grade Ib (34.1%), grade 2(15.0%) and grade 3 (4.0%). Prevalence increased with increase in age. Statistically significant differences were found in the prevalence of endemic goitre in relation to different religions and caste groups, different occupations of the parents/guardians of children and types of houses used for the purpose of living. PMID:8138288

  9. Socioeconomic networks with long-range interactions

    NASA Astrophysics Data System (ADS)

    Carvalho, Rui; Iori, Giulia

    2008-07-01

    We study a modified version of a model previously proposed by Jackson and Wolinsky to account for communication of information and allocation of goods in socioeconomic networks. In the model, the utility function of each node is given by a weighted sum of contributions from all accessible nodes. The weights, parametrized by the variable δ , decrease with distance. We introduce a growth mechanism where new nodes attach to the existing network preferentially by utility. By increasing δ , the network structure evolves from a power-law to an exponential degree distribution, passing through a regime characterized by shorter average path length, lower degree assortativity, and higher central point dominance. In the second part of the paper we compare different network structures in terms of the average utility received by each node. We show that power-law networks provide higher average utility than Poisson random networks. This provides a possible justification for the ubiquitousness of scale-free networks in the real world.

  10. Associations Between Socioeconomic Factors and Alcohol Outcomes

    PubMed Central

    Collins, Susan E.

    2016-01-01

    Socioeconomic status (SES) is one of the many factors influencing a person’s alcohol use and related outcomes. Findings have indicated that people with higher SES may consume similar or greater amounts of alcohol compared with people with lower SES, although the latter group seems to bear a disproportionate burden of negative alcohol-related consequences. These associations are further complicated by a variety of moderating factors, such as race, ethnicity, and gender. Thus, among individuals with lower SES, members of further marginalized communities, such as racial and ethnic minorities and homeless individuals, experience greater alcohol-related consequences. Future studies are needed to more fully explore the underlying mechanisms of the relationship between SES and alcohol outcomes. This knowledge should be applied toward the development of multilevel interventions that address not only individual-level risks but also economic disparities that have precipitated and maintained a disproportionate level of alcohol-related consequences among more marginalized and vulnerable populations. PMID:27159815

  11. The early education of socioeconomically disadvantaged children.

    PubMed

    Arnold, David H; Doctoroff, Greta L

    2003-01-01

    This chapter reviews selected research on the education of low-socioeconomic status (SES) children from birth through the first years of elementary school. Themes include the importance of early academic skills and interest to later achievement; the benefits of integrating knowledge from research on mental health and other areas; the need to utilize and build children's strengths as well as address their weaknesses; and a call to connect research to practice and policy. Relevant research on race and culture is reviewed because ethnic minority low-SES children are at great risk of poverty. Gender is discussed because low-SES boys have poorer general achievement than girls, while very few low-SES girls pursue careers in math- and science-related fields.

  12. Associations Between Socioeconomic Factors and Alcohol Outcomes.

    PubMed

    Collins, Susan E

    2016-01-01

    Socioeconomic status (SES) is one of the many factors influencing a person's alcohol use and related outcomes. Findings have indicated that people with higher SES may consume similar or greater amounts of alcohol compared with people with lower SES, although the latter group seems to bear a disproportionate burden of negative alcohol-related consequences. These associations are further complicated by a variety of moderating factors, such as race, ethnicity, and gender. Thus, among individuals with lower SES, members of further marginalized communities, such as racial and ethnic minorities and homeless individuals, experience greater alcohol-related consequences. Future studies are needed to more fully explore the underlying mechanisms of the relationship between SES and alcohol outcomes. This knowledge should be applied toward the development of multilevel interventions that address not only individual-level risks but also economic disparities that have precipitated and maintained a disproportionate level of alcohol-related consequences among more marginalized and vulnerable populations. PMID:27159815

  13. Socioeconomic Status, Family Processes, and Individual Development

    PubMed Central

    Conger, Rand D.; Conger, Katherine J.; Martin, Monica J.

    2010-01-01

    Research during the past decade shows that social class or socioeconomic status (SES) is related to satisfaction and stability in romantic unions, the quality of parent-child relationships, and a range of developmental outcomes for adults and children. This review focuses on evidence regarding potential mechanisms proposed to account for these associations. Research findings reported during the past decade demonstrate support for an interactionist model of the relationship between SES and family life, which incorporates assumptions from both the social causation and social selection perspectives. The review concludes with recommendations for future research on SES, family processes and individual development in terms of important theoretical and methodological issues yet to be addressed. PMID:20676350

  14. Marriage and Socioeconomic Change in Contemporary Indonesia

    PubMed Central

    Nobles, Jenna; Buttenheim, Alison

    2015-01-01

    This study investigates the relationship between economic trends and entry into marriage in a rapidly developing setting. We examine Indonesian marriage in the 1990’s, a decade of substantial economic growth followed by a sudden financial collapse in 1998. We use discrete-time hazard models to analyze information on 4,078 women and 4,496 men from the Indonesia Family Life Survey. While previous research has shown that marriages may be postponed after economic downturn, we find no evidence of such delays at the national level following the 1998 financial crisis. In contrast, we use regional wage rate data to show that entry into marriage is inversely related to economic growth throughout the decade for all women and for men from lower socioeconomic strata. PMID:26336321

  15. "I Am-We Are": Personal and Social Pathways to Further Study, Work and Family Life

    ERIC Educational Resources Information Center

    Bornholt, L. J.; Maras, P. M.; Robinson, R. A.

    2009-01-01

    This project explores the apparent layers in motivation for young people's plans in order to extend Pathways Theory. We bring together personal, relational and group motivation to explain the planned pathways to study, work and family life. Location was an Australian town, close to the national socio-economic average, to control broad social…

  16. Childhood socioeconomic position and adult leisure-time physical activity: a systematic review.

    PubMed

    Elhakeem, Ahmed; Cooper, Rachel; Bann, David; Hardy, Rebecca

    2015-01-01

    Regular leisure-time physical activity (LTPA) benefits health and is thought to be less prevalent in lower socioeconomic groups. Evidence suggests that childhood socioeconomic circumstances can impact on adult health and behaviour however, it is unclear if this includes an influence on adult LTPA. This review tested the hypothesis that a lower childhood socioeconomic position (SEP) is associated with less frequent LTPA during adulthood. Studies were located through a systematic search of MEDLINE, Embase, PsycINFO, CINAHL and SPORTDiscus and by searching reference lists. Eligible studies were English-language publications testing the association between any indicator of childhood SEP and an LTPA outcome measured during adulthood. Forty-five papers from 36 studies, most of which were European, were included. In most samples, childhood SEP and LTPA were self-reported in midlife. Twenty-two studies found evidence to support the review's hypothesis and thirteen studies found no association. Accounting for own adult SEP partly attenuated associations. There was more evidence of an association in British compared with Scandinavian cohorts and in women compared with men. Results did not vary by childhood SEP indicator or age at assessment of LTPA. This review found evidence of an association between less advantaged childhood SEP and less frequent LTPA during adulthood. Understanding how associations vary by gender and place could provide insights into underlying pathways.

  17. Socioeconomic inequalities in access to treatment for coronary heart disease: A systematic review.

    PubMed

    Schröder, Sara L; Richter, Matthias; Schröder, Jochen; Frantz, Stefan; Fink, Astrid

    2016-09-15

    Strong socioeconomic inequalities exist in cardiovascular mortality and morbidity. The current review aims to synthesize the current evidence on the association between socioeconomic status (SES) and access to treatment of coronary heart disease (CHD). We examined quantitative studies analyzing the relationship between SES and access to CHD treatment that were published between 1996 and 2015. Our data sources included Medline and Web of Science. Our search yielded a total of 2066 records, 57 of which met our inclusion criteria. Low SES was found to be associated with low access to coronary procedures and secondary prevention. Access to coronary procedures, especially coronary angiography, was mainly related to SES to the disadvantage of patients with low SES. However, access to drug treatment and cardiac rehabilitation was only associated with SES in about half of the studies. The association between SES and access to treatment for CHD was stronger when SES was measured based on individual-level compared to area level, and stronger for individuals living in countries without universal health coverage. Socioeconomic inequalities exist in access to CHD treatment, and universal health coverage shows only a minor effect on this relationship. Inequalities diminish along the treatment pathway for CHD from diagnostic procedures to secondary prevention. We therefore conclude that CHD might be underdiagnosed in patients with low SES. Our results indicate that there is an urgent need to improve access to CHD treatment, especially by increasing the supply of diagnostic angiographies, to reduce inequalities across different healthcare systems.

  18. Childhood socioeconomic position and adult leisure-time physical activity: a systematic review.

    PubMed

    Elhakeem, Ahmed; Cooper, Rachel; Bann, David; Hardy, Rebecca

    2015-01-01

    Regular leisure-time physical activity (LTPA) benefits health and is thought to be less prevalent in lower socioeconomic groups. Evidence suggests that childhood socioeconomic circumstances can impact on adult health and behaviour however, it is unclear if this includes an influence on adult LTPA. This review tested the hypothesis that a lower childhood socioeconomic position (SEP) is associated with less frequent LTPA during adulthood. Studies were located through a systematic search of MEDLINE, Embase, PsycINFO, CINAHL and SPORTDiscus and by searching reference lists. Eligible studies were English-language publications testing the association between any indicator of childhood SEP and an LTPA outcome measured during adulthood. Forty-five papers from 36 studies, most of which were European, were included. In most samples, childhood SEP and LTPA were self-reported in midlife. Twenty-two studies found evidence to support the review's hypothesis and thirteen studies found no association. Accounting for own adult SEP partly attenuated associations. There was more evidence of an association in British compared with Scandinavian cohorts and in women compared with men. Results did not vary by childhood SEP indicator or age at assessment of LTPA. This review found evidence of an association between less advantaged childhood SEP and less frequent LTPA during adulthood. Understanding how associations vary by gender and place could provide insights into underlying pathways. PMID:26138985

  19. The Integration of Remote Sensing and Socioeconomic Data: Lessons from the Socioeconomic Data and Applications Center

    NASA Astrophysics Data System (ADS)

    de Sherbinin, A. M.; Chen, R. S.

    2014-12-01

    Many of the core research questions of the "anthropocene" are spatial in nature, and require spatial data integration to provide the answers: Where are the people most vulnerable to environmental changes located? How do global environmental changes affect people, ecosystems or production systems in a given location? What are the impacts of human activities in the coastal zone, or mountainous areas, or drylands? This paper provides examples of the integration of remotely sensed biophysical and socioeconomic data that illustrate the benefits of spatial data integration. It also addresses some of the challenges in integrating data developed at different scales and for different purposes, sharing lessons learned from twenty years of operating the NASA Socioeconomic Data and Applications Center (SEDAC). Examples will be drawn from the literature on land use/land cover change, urbanization, disaster risk management, climate impact and vulnerability assessment, and natural resource management.

  20. Density and type of food retailers surrounding Canadian schools: variations across socioeconomic status.

    PubMed

    Seliske, Laura M; Pickett, William; Boyce, William F; Janssen, Ian

    2009-09-01

    Lower socioeconomic status (SES) neighbourhoods may have differential access to food retailers, potentially explaining the varying area-level obesity rates. The food retail environment around 188 schools across Canada was examined, including full-service restaurants, fast food restaurants, sub/sandwich retailers, donut/coffee shops, convenience stores, and grocery stores. School addresses were linked to census data to obtain area-level SES measures. Access to food retailers was generally not associated with the neighbourhood SES in the immediate proximity. Within the broader neighbourhood, lower SES neighbourhoods had access to fewer food retailers of all types. This effect was diminished after taking population density into account. PMID:19121973

  1. Measurement of socio-economic status in families of children with cancer in Guatemala.

    PubMed

    De Pernillo, M; Rivas, S; Fuentes, L; Antillon, F; Barr, R D

    2014-11-01

    The prospects for survival of children in low and middle income countries are linked to their families socio-economic status (SES), of which income is only one component. Developing a comprehensive measure of SES is required. Informed by clinical experience, a 15-item instrument was designed in Guatemala to categorize SES by five levels in each item. Almost 75% of families attending the Unidad Nacional de Oncología Pediátrica were in the lowest three of six categories, providing a framework for stratified financial and nutritional support. The measure of SES offers an opportunity for examining associations with health outcomes throughout Latin America.

  2. Child Health, Maternal Marital and Socioeconomic Factors, and Maternal Health

    ERIC Educational Resources Information Center

    Garbarski, Dana; Witt, Whitney P.

    2013-01-01

    Although maternal socioeconomic status and health predict in part children's future health and socioeconomic prospects, it is possible that the intergenerational association flows in the other direction such that child health affects maternal outcomes. Previous research demonstrates that poor child health increases the risk of adverse…

  3. 10 CFR 960.5-2-6 - Socioeconomic impacts.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Socioeconomic impacts. 960.5-2-6 Section 960.5-2-6 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Preclosure Guidelines Environment, Socioeconomics, and Transportation § 960.5-2-6...

  4. Racial and Socioeconomic Disparities in Nutrition Behaviors: Targeted Interventions Needed

    ERIC Educational Resources Information Center

    Fahlman, Mariane M.; McCaughtry, Nate; Martin, Jeffrey; Shen, Bo

    2010-01-01

    Objective: To compare dietary knowledge, behaviors and self-efficacy of black middle school students of low socioeconomic status with their white counterparts of higher socioeconomic status. Design: Cross-sectional, school-based survey. Setting: Large metropolitan area in the United States. Participants: Middle school students (1,208 of low…

  5. Accounting for Socioeconomic Differences in Delaying the Transition to College

    ERIC Educational Resources Information Center

    Goldrick-Rab, Sara; Han, Seong Won

    2011-01-01

    Despite popular conceptions of the "gap year" as a time of personal enrichment, the incidence of delay between high school and college is greatest among students from socioeconomically disadvantaged families, suggesting other motivations. This article examines two explanations for socioeconomic inequalities in rates of delay: disparities in high…

  6. Family Socioeconomic Status and Adolescent Sex-Typing.

    ERIC Educational Resources Information Center

    McCandless, N. Jane; And Others

    1989-01-01

    Reexamined relationship between sex-role differentiation and family socioeconomic status. Analyzed attitudinal and behavior data of high school seniors (N=5600) to determine validity of hypothesis that sex-role differentiation is more pronounced in lower socioeconomic status groups. Found sex-role differentiation greater among higher socioeconomic…

  7. Socioeconomic Status and Injury in a Cohort of Saskatchewan Farmers

    ERIC Educational Resources Information Center

    Pickett, William; Day, Andrew G.; Hagel, Louise; Sun, Xiaoqun; Day, Lesley; Marlenga, Barbara; Brison, Robert J.; Pahwa, Punam; Crowe, Trever; Voaklander, Donald C.; Dosman, James

    2011-01-01

    Purpose: To estimate the strength of relationships between socioeconomic status and injury in a large Canadian farm population. Methods: We conducted a prospective cohort study of 4,769 people from 2,043 farms in Saskatchewan, Canada. Participants reported socioeconomic exposures in 2007 and were followed for the occurrence of injury through 2009…

  8. The Relationship Between Socioeconomic Variables and State Effort for Education

    ERIC Educational Resources Information Center

    Sparkman, William E.

    1977-01-01

    Examines the relationship between selected socioeconomic data and state effort for the support of public schools among the 50 states. Two measures of state effort are identified for use as dependent variables, and multiple regression analysis is used to determine the relationship between socioeconomic factors and state effort for education.…

  9. Child Maltreatment and Adult Socioeconomic Well-Being

    ERIC Educational Resources Information Center

    Zielinski, David S.

    2009-01-01

    Objective: Little empirical research has examined the impact that child maltreatment may have on victims' long-term socioeconomic well-being. The current study sought to address this gap by exploring the relationship between childhood experiences of abuse and neglect and several indicators of socioeconomic well-being in adulthood. Method: Data…

  10. The digital traces of bubbles: feedback cycles between socio-economic signals in the Bitcoin economy.

    PubMed

    Garcia, David; Tessone, Claudio J; Mavrodiev, Pavlin; Perony, Nicolas

    2014-10-01

    What is the role of social interactions in the creation of price bubbles? Answering this question requires obtaining collective behavioural traces generated by the activity of a large number of actors. Digital currencies offer a unique possibility to measure socio-economic signals from such digital traces. Here, we focus on Bitcoin, the most popular cryptocurrency. Bitcoin has experienced periods of rapid increase in exchange rates (price) followed by sharp decline; we hypothesize that these fluctuations are largely driven by the interplay between different social phenomena. We thus quantify four socio-economic signals about Bitcoin from large datasets: price on online exchanges, volume of word-of-mouth communication in online social media, volume of information search and user base growth. By using vector autoregression, we identify two positive feedback loops that lead to price bubbles in the absence of exogenous stimuli: one driven by word of mouth, and the other by new Bitcoin adopters. We also observe that spikes in information search, presumably linked to external events, precede drastic price declines. Understanding the interplay between the socio-economic signals we measured can lead to applications beyond cryptocurrencies to other phenomena that leave digital footprints, such as online social network usage.

  11. The digital traces of bubbles: feedback cycles between socio-economic signals in the Bitcoin economy.

    PubMed

    Garcia, David; Tessone, Claudio J; Mavrodiev, Pavlin; Perony, Nicolas

    2014-10-01

    What is the role of social interactions in the creation of price bubbles? Answering this question requires obtaining collective behavioural traces generated by the activity of a large number of actors. Digital currencies offer a unique possibility to measure socio-economic signals from such digital traces. Here, we focus on Bitcoin, the most popular cryptocurrency. Bitcoin has experienced periods of rapid increase in exchange rates (price) followed by sharp decline; we hypothesize that these fluctuations are largely driven by the interplay between different social phenomena. We thus quantify four socio-economic signals about Bitcoin from large datasets: price on online exchanges, volume of word-of-mouth communication in online social media, volume of information search and user base growth. By using vector autoregression, we identify two positive feedback loops that lead to price bubbles in the absence of exogenous stimuli: one driven by word of mouth, and the other by new Bitcoin adopters. We also observe that spikes in information search, presumably linked to external events, precede drastic price declines. Understanding the interplay between the socio-economic signals we measured can lead to applications beyond cryptocurrencies to other phenomena that leave digital footprints, such as online social network usage. PMID:25100315

  12. What is the impact of socio-economic inequalities on the use of mental health services?

    PubMed

    Amaddeo, Francesco; Jones, Julia

    2007-01-01

    Amartya Sen, who received the Nobel Prize for Economics, has demonstrated that the incidence of deprivation, in terms of capability, can be surprisingly high even in the most developed countries of the world. The study of socio-economic inequalities, in relation to the utilisation of health services, is a priority for epidemiological research. Socio-economic status (SES) has no universal definition. Within the international research literature, SES has been related to social class, social position, occupational status, educational attainment, income, wealth and standard of living. Existing research studies have shown that people from a more deprived social background, with a lower SES, are more likely to have a higher psychiatric morbidity. Many studies show that SES influences psychiatric services utilization, however the real factors linking SES and mental health services utilisation remain unclear. In this editorial we discuss what is currently known about the relationship between SES and the use of mental health services. We also make an argument for why we believe there is still much to uncover in this field, to understand fully how individuals are influenced by their personal socio-economic status, or the neighbourhood in which they live, in terms of their use of mental health services. Further research in this area will help clarify what interventions are required to provide greater equality in access to mental health services.

  13. The digital traces of bubbles: feedback cycles between socio-economic signals in the Bitcoin economy

    PubMed Central

    Garcia, David; Tessone, Claudio J.; Mavrodiev, Pavlin; Perony, Nicolas

    2014-01-01

    What is the role of social interactions in the creation of price bubbles? Answering this question requires obtaining collective behavioural traces generated by the activity of a large number of actors. Digital currencies offer a unique possibility to measure socio-economic signals from such digital traces. Here, we focus on Bitcoin, the most popular cryptocurrency. Bitcoin has experienced periods of rapid increase in exchange rates (price) followed by sharp decline; we hypothesize that these fluctuations are largely driven by the interplay between different social phenomena. We thus quantify four socio-economic signals about Bitcoin from large datasets: price on online exchanges, volume of word-of-mouth communication in online social media, volume of information search and user base growth. By using vector autoregression, we identify two positive feedback loops that lead to price bubbles in the absence of exogenous stimuli: one driven by word of mouth, and the other by new Bitcoin adopters. We also observe that spikes in information search, presumably linked to external events, precede drastic price declines. Understanding the interplay between the socio-economic signals we measured can lead to applications beyond cryptocurrencies to other phenomena that leave digital footprints, such as online social network usage. PMID:25100315

  14. Socioeconomic Disparities in the Use of Home Health Services in a Medicare Managed Care Population

    PubMed Central

    Freedman, Vicki A; Rogowski, Jeannette; Wickstrom, Steven L; Adams, John; Marainen, Jonas; Escarce, José J

    2004-01-01

    Objective To investigate socioeconomic disparities in access to home health visits and durable medical equipment by persons enrolled in two Medicare managed care health plans. Data Sources A telephone survey of 4,613 Medicare managed care enrollees conducted between April and October of 2000 and linked to administrative claims for a subsequent 12-month period. Study Design We estimated a series of logistic regression models to determine which socioeconomic factors were related to home health visits and the use of durable medical equipment (DME) among Medicare managed care enrollees. Principal Findings Controlling for health and demographic differences, Medicare managed care enrollees in the lowest tertile for nonhousing assets had 50 percent greater odds than those in the highest tertile of having one or more home health visits. All else equal, enrollees with less than a high school education had 30 percent lower odds than those who had graduated from high school of using durable medical equipment. Conclusions Medicare managed care enrollees of low socioeconomic status do not appear to have reduced access to home health visits; however, use of durable medical equipment is considerably lower for enrollees with less than a high school education. Physicians and therapists working with Medicare managed care enrollees may want to actively target DME prescriptions to those with educational disadvantages. PMID:15333109

  15. Neighbourhood socioeconomic inequalities in incidence of acute myocardial infarction: a cohort study quantifying age- and gender-specific differences in relative and absolute terms

    PubMed Central

    2012-01-01

    Background Socioeconomic status has a profound effect on the risk of having a first acute myocardial infarction (AMI). Information on socioeconomic inequalities in AMI incidence across age- gender-groups is lacking. Our objective was to examine socioeconomic inequalities in the incidence of AMI considering both relative and absolute measures of risk differences, with a particular focus on age and gender. Methods We identified all patients with a first AMI from 1997 to 2007 through linked hospital discharge and death records covering the Dutch population. Relative risks (RR) of AMI incidence were estimated by mean equivalent household income at neighbourhood-level for strata of age and gender using Poisson regression models. Socioeconomic inequalities were also shown within the stratified age-gender groups by calculating the total number of events attributable to socioeconomic disadvantage. Results Between 1997 and 2007, 317,564 people had a first AMI. When comparing the most deprived socioeconomic quintile with the most affluent quintile, the overall RR for AMI was 1.34 (95 % confidence interval (CI): 1.32 – 1.36) in men and 1.44 (95 % CI: 1.42 – 1.47) in women. The socioeconomic gradient decreased with age. Relative socioeconomic inequalities were most apparent in men under 35 years and in women under 65 years. The largest number of events attributable to socioeconomic inequalities was found in men aged 45–74 years and in women aged 65–84 years. The total proportion of AMIs that was attributable to socioeconomic inequalities in the Dutch population of 1997 to 2007 was 14 % in men and 18 % in women. Conclusions Neighbourhood socioeconomic inequalities were observed in AMI incidence in the Netherlands, but the magnitude across age-gender groups depended on whether inequality was expressed in relative or absolute terms. Relative socioeconomic inequalities were high in young persons and women, where the absolute burden of AMI was low. Absolute

  16. Socio-economic inequality of immunization coverage in India.

    PubMed

    Lauridsen, Jørgen; Pradhan, Jalandhar

    2011-08-05

    To our knowledge, the present study provides a first time assessment of the contributions of socioeconomic determinants of immunization coverage in India using the recent National Family Health Survey data. Measurement of socioeconomic inequalities in health and health care, and understanding the determinants of such inequalities in terms of their contributions, are critical for health intervention strategies and for achieving equity in health care. A decomposition approach is applied to quantify the contributions from socio-demographic factors to inequality in immunization coverage. The results reveal that poor household economic status, mother's illiteracy, per capita state domestic product and proportion of illiterate at the state level is systematically related to 97% of predictable socioeconomic inequalities in full immunization coverage at the national level. These patterns of evidence suggest the need for immunization strategies targeted at different states and towards certain socioeconomic determinants as pointed out above in order to reduce socioeconomic inequalities in immunization coverage.JEL Classification: I10, I12.

  17. Socio-economic and climate change impacts on agriculture: an integrated assessment, 1990-2080.

    PubMed

    Fischer, Günther; Shah, Mahendra; Tubiello, Francesco N; van Velhuizen, Harrij

    2005-11-29

    A comprehensive assessment of the impacts of climate change on agro-ecosystems over this century is developed, up to 2080 and at a global level, albeit with significant regional detail. To this end an integrated ecological-economic modelling framework is employed, encompassing climate scenarios, agro-ecological zoning information, socio-economic drivers, as well as world food trade dynamics. Specifically, global simulations are performed using the FAO/IIASA agro-ecological zone model, in conjunction with IIASAs global food system model, using climate variables from five different general circulation models, under four different socio-economic scenarios from the intergovernmental panel on climate change. First, impacts of different scenarios of climate change on bio-physical soil and crop growth determinants of yield are evaluated on a 5' X 5' latitude/longitude global grid; second, the extent of potential agricultural land and related potential crop production is computed. The detailed bio-physical results are then fed into an economic analysis, to assess how climate impacts may interact with alternative development pathways, and key trends expected over this century for food demand and production, and trade, as well as key composite indices such as risk of hunger and malnutrition, are computed. This modelling approach connects the relevant bio-physical and socio-economic variables within a unified and coherent framework to produce a global assessment of food production and security under climate change. The results from the study suggest that critical impact asymmetries due to both climate and socio-economic structures may deepen current production and consumption gaps between developed and developing world; it is suggested that adaptation of agricultural techniques will be central to limit potential damages under climate change.

  18. Socio-economic and climate change impacts on agriculture: an integrated assessment, 1990–2080

    PubMed Central

    Fischer, Günther; Shah, Mahendra; N. Tubiello, Francesco; van Velhuizen, Harrij

    2005-01-01

    A comprehensive assessment of the impacts of climate change on agro-ecosystems over this century is developed, up to 2080 and at a global level, albeit with significant regional detail. To this end an integrated ecological–economic modelling framework is employed, encompassing climate scenarios, agro-ecological zoning information, socio-economic drivers, as well as world food trade dynamics. Specifically, global simulations are performed using the FAO/IIASA agro-ecological zone model, in conjunction with IIASAs global food system model, using climate variables from five different general circulation models, under four different socio-economic scenarios from the intergovernmental panel on climate change. First, impacts of different scenarios of climate change on bio-physical soil and crop growth determinants of yield are evaluated on a 5′×5′ latitude/longitude global grid; second, the extent of potential agricultural land and related potential crop production is computed. The detailed bio-physical results are then fed into an economic analysis, to assess how climate impacts may interact with alternative development pathways, and key trends expected over this century for food demand and production, and trade, as well as key composite indices such as risk of hunger and malnutrition, are computed. This modelling approach connects the relevant bio-physical and socio-economic variables within a unified and coherent framework to produce a global assessment of food production and security under climate change. The results from the study suggest that critical impact asymmetries due to both climate and socio-economic structures may deepen current production and consumption gaps between developed and developing world; it is suggested that adaptation of agricultural techniques will be central to limit potential damages under climate change. PMID:16433094

  19. The role of socioeconomic status in longitudinal trends of cholera in Matlab, Bangladesh, 1993-2007.

    PubMed

    Root, Elisabeth Dowling; Rodd, Joshua; Yunus, Mohammad; Emch, Michael

    2013-01-01

    There has been little evidence of a decline in the global burden of cholera in recent years as the number of cholera cases reported to WHO continues to rise. Cholera remains a global threat to public health and a key indicator of lack of socioeconomic development. Overall socioeconomic development is the ultimate solution for control of cholera as evidenced in developed countries. However, most research has focused on cross-county comparisons so that the role of individual- or small area-level socioeconomic status (SES) in cholera dynamics has not been carefully studied. Reported cases of cholera in Matlab, Bangladesh have fluctuated greatly over time and epidemic outbreaks of cholera continue, most recently with the introduction of a new serotype into the region. The wealth of longitudinal data on the population of Matlab provides a unique opportunity to explore the impact of socioeconomic status and other demographic characteristics on the long-term temporal dynamics of cholera in the region. In this population-based study we examine which factors impact the initial number of cholera cases in a bari at the beginning of the 0139 epidemic and the factors impacting the number of cases over time. Cholera data were derived from the ICDDR,B health records and linked to socioeconomic and geographic data collected as part of the Matlab Health and Demographic Surveillance System. Longitudinal zero-inflated Poisson (ZIP) multilevel regression models are used to examine the impact of environmental and socio-demographic factors on cholera counts across baris. Results indicate that baris with a high socioeconomic status had lower initial rates of cholera at the beginning of the 0139 epidemic (γ(01) = -0.147, p = 0.041) and a higher probability of reporting no cholera cases (α(01) = 0.156, p = 0.061). Populations in baris characterized by low SES are more likely to experience higher cholera morbidity at the beginning of an epidemic than populations in high

  20. The Role of Socioeconomic Status in Longitudinal Trends of Cholera in Matlab, Bangladesh, 1993–2007

    PubMed Central

    Root, Elisabeth Dowling; Rodd, Joshua; Yunus, Mohammad; Emch, Michael

    2013-01-01

    There has been little evidence of a decline in the global burden of cholera in recent years as the number of cholera cases reported to WHO continues to rise. Cholera remains a global threat to public health and a key indicator of lack of socioeconomic development. Overall socioeconomic development is the ultimate solution for control of cholera as evidenced in developed countries. However, most research has focused on cross-county comparisons so that the role of individual- or small area-level socioeconomic status (SES) in cholera dynamics has not been carefully studied. Reported cases of cholera in Matlab, Bangladesh have fluctuated greatly over time and epidemic outbreaks of cholera continue, most recently with the introduction of a new serotype into the region. The wealth of longitudinal data on the population of Matlab provides a unique opportunity to explore the impact of socioeconomic status and other demographic characteristics on the long-term temporal dynamics of cholera in the region. In this population-based study we examine which factors impact the initial number of cholera cases in a bari at the beginning of the 0139 epidemic and the factors impacting the number of cases over time. Cholera data were derived from the ICDDR,B health records and linked to socioeconomic and geographic data collected as part of the Matlab Health and Demographic Surveillance System. Longitudinal zero-inflated Poisson (ZIP) multilevel regression models are used to examine the impact of environmental and socio-demographic factors on cholera counts across baris. Results indicate that baris with a high socioeconomic status had lower initial rates of cholera at the beginning of the 0139 epidemic (γ01 = −0.147, p = 0.041) and a higher probability of reporting no cholera cases (α01 = 0.156, p = 0.061). Populations in baris characterized by low SES are more likely to experience higher cholera morbidity at the beginning of an epidemic than populations in high SES

  1. Clerkship pathway

    PubMed Central

    MacLellan, Anne-Marie; Brailovsky, Carlos; Miller, François; Leboeuf, Sylvie

    2012-01-01

    Abstract Objective To identify factors that help predict success for international medical graduates (IMGs) who train in Canadian residency programs and pass the Canadian certification examinations. Design A retrospective analysis of 58 variables in the files of IMGs who applied to the Collège des médecins du Québec between 2000 and 2008. Setting Quebec. Participants Eight hundred ten IMGs who applied to the Collège des médecins du Québec through either the “equivalency pathway” (ie, starting training at a residency level) or the “clerkship pathway” (ie, relearning at the level of a medical student in the last 2 years of the MD diploma). Main outcome measures Success factors in achieving certification. Data were analyzed using descriptive statistics and ANOVA (analysis of variance). Results International medical graduates who chose the “clerkship pathway” had greater success on certification examinations than those who started at the residency level did. Conclusion There are several factors that influence IMGs’ success on certification examinations, including integration issues, the acquisition of clinical decision-making skills, and the varied educational backgrounds. These factors perhaps can be better addressed by a regular clerkship pathway, in which IMGs benefit from learner-centred teaching and have more time for reflection on and understanding of the North American approach to medical education. The clerkship pathway is a useful strategy for assuring the integration of IMGs in the North American health care system. A 2-year relearning period in medical school at a clinical clerkship level deserves careful consideration. PMID:22859630

  2. Hostility and anomie: links to preterm delivery subtypes and ambulatory blood pressure at mid-pregnancy.

    PubMed

    Tiedje, LindaBeth; Holzman, Claudia B; De Vos, Eric; Jia, Xu; Korzeniewski, Steve; Rahbar, Mohammad H; Goble, Monica M; Kallen, David

    2008-03-01

    Underlying maternal vascular disease has been implicated as one of several pathways contributing to preterm delivery (PTD) and psychosocial factors such as hostility, anomie, effortful coping, and mastery may be associated with PTD by affecting maternal vascular health. Using data from the Pregnancy Outcomes and Community Health (POUCH) study, we included 2018 non-Hispanic White and 743 African American women from 52 clinics in five Michigan, USA communities. Women were interviewed at 15-27 weeks' gestation and followed to delivery. We found that relations between psychosocial factors and PTD subtypes (i.e. medically indicated, premature rupture of membranes, spontaneous labor) varied by race/ethnicity and socio-economic position (Medicaid insurance status). Among African American women not insured by Medicaid, anomie levels in mid-pregnancy were positively associated with medically indicated PTD after adjusting for maternal age and education. Among all women not insured by Medicaid, hostility levels were positively associated with spontaneous PTD after adjusting for maternal race/ethnicity, age, and education. Failure to detect links between psychosocial factors and PTD risk in poorer women may be due to their excess risk in multiple PTD pathways and/or a more complex web of contributing risk factors. In a subset of 395 women monitored for blood pressure, anomie scores were positively associated with systolic blood pressure and heart rate and hostility scores were positively associated with systolic and diastolic blood pressure, heart rate and mean arterial pressure in models that included time, awake/asleep, race/ethnicity, and age as covariates. Further adjustment for body mass index and smoking attenuated the anomie-vascular relations but had little effect on the hostility-vascular relations. Overall this study of pregnant women provides some physiologic evidence to support findings linking levels of anomie and hostility with risk of PTD.

  3. Ethnic and socioeconomic trends in breast cancer incidence in New Zealand

    PubMed Central

    2010-01-01

    Background Breast cancer incidence varies between social groups, but differences have not been thoroughly examined in New Zealand. The objectives of this study are to determine whether trends in breast cancer incidence varied by ethnicity and socioeconomic position between 1981 and 2004 in New Zealand, and to assess possible risk factor explanations. Methods Five cohorts of the entire New Zealand population for 1981-86, 1986-1991, 1991-1996, 1996-2001, and 2001-2004 were created, and probabilistically linked to cancer registry records, allowing direct determination of ethnic and socioeconomic trends in breast cancer incidence. Results Breast cancer rates increased across all ethnic and socioeconomic groups between 1981 and 2004. Māori women consistently had the highest age standardised rates, and the difference between Māori and European/Other women increased from 7% in 1981-6 to 24% in 2001-4. Pacific and Asian women had consistently lower rates of breast cancer than European/Other women over the time period studied (12% and 28% lower respectively when pooled over time), although young Pacific women had slightly higher incidence rates than young European/other women. A gradient between high and low income women was evident, with high income women having breast cancer rates approximately 10% higher and this difference did not change significantly over time. Conclusions Differences in breast cancer incidence between European and Pacific women and between socioeconomic groups are explicable in terms of known risk factors. However no straightforward explanation for the relatively high incidence amongst Māori is apparent. Further research to explore high Māori breast cancer rates may contribute to reducing the burden of breast cancer amongst Māori women, as well as improving our understanding of the aetiology of breast cancer. PMID:21138590

  4. The effect of socioeconomic deprivation on fracture incidence in the United Kingdom.

    PubMed

    Jones, Sarah; Johansen, Antony; Brennan, Julieann; Butler, John; Lyons, Ronan A

    2004-07-01

    Lifestyle factors such as diet and physical activity vary in different social and income groups, and are known to be important influences on the incidence of osteoporotic fractures. Financial and social pressures are a common concern for older people. We set out to study the effect of socioeconomic deprivation on the incidence of fracture in older people and to compare the findings with those for younger groups. The All Wales Injury Surveillance System (AWISS) is a computerized system that collects injury data from most A&E departments throughout Wales. In this population-based study of 1.8 million people living in the 445 electoral tracts covered by AWISS in south, west, and northeastern Wales, we identified all 60,106 residents who presented with a fracture in 1999 and 2000. We linked details of their fracture with published Townsend deprivation scores for the electoral tract in which they were living and calculated fracture rates by fifths of deprivation. We observed the expected pattern of increasing fracture incidence in older age groups. Fracture incidence was significantly higher in electoral wards with poorer Townsend scores, resulting from a marked effect of socioeconomic deprivation on fracture incidence among younger adults with a rate ratio of 1.64 (95% CI, 1.57 to 1.72). This effect diminished with age, and was not observed in older age groups. At ages 85 and over the rate ratio was 0.94 (95% CI, 0.87 to 1.01). Socioeconomic factors clearly play a part in the causation of fracture in younger adults. Lifestyle influences are important in older age groups, but socioeconomic deprivation does not appear to be a risk factor for the development of osteoporotic fractures in elderly people. PMID:15057509

  5. Understanding socio-economic inequalities in food choice behaviour: can Maslow's pyramid help?

    PubMed

    van Lenthe, Frank J; Jansen, Tessa; Kamphuis, Carlijn B M

    2015-04-14

    Socio-economic groups differ in their material, living, working and social circumstances, which may result in different priorities about their daily-life needs, including the priority to make healthy food choices. Following Maslow's hierarchy of human needs, we hypothesised that socio-economic inequalities in healthy food choices can be explained by differences in the levels of need fulfilment. Postal survey data collected in 2011 (67·2 % response) from 2903 participants aged 20-75 years in the Dutch GLOBE (Gezondheid en Levens Omstandigheden Bevolking Eindhoven en omstreken) study were analysed. Maslow's hierarchy of human needs (measured with the Basic Need Satisfaction Inventory) was added to age- and sex-adjusted linear regression models that linked education and net household income levels to healthy food choices (measured by a FFQ). Most participants (38·6 %) were in the self-actualisation layer of the pyramid. This proportion was highest among the highest education group (47·6 %). Being in a higher level of the hierarchy was associated with a higher consumption of fruits and vegetables as well as more healthy than unhealthy bread, snack and dairy consumption. Educational inequalities in fruit and vegetable intake (B= -1·79, 95 % CI -2·31, -1·28 in the lowest education group) were most reduced after the hierarchy of needs score was included (B= -1·57, 95 % CI - ·09, -1·05). Inequalities in other healthy food choices hardly changed after the hierarchy of needs score was included. People who are satisfied with higher-level needs make healthier food choices. Studies aimed at understanding socio-economic inequalities in food choice behaviour need to take differences in the priority given to daily-life needs by different socio-economic groups into account, but Maslow's pyramid offers little help. PMID:25784199

  6. The effect of socioeconomic deprivation on fracture incidence in the United Kingdom.

    PubMed

    Jones, Sarah; Johansen, Antony; Brennan, Julieann; Butler, John; Lyons, Ronan A

    2004-07-01

    Lifestyle factors such as diet and physical activity vary in different social and income groups, and are known to be important influences on the incidence of osteoporotic fractures. Financial and social pressures are a common concern for older people. We set out to study the effect of socioeconomic deprivation on the incidence of fracture in older people and to compare the findings with those for younger groups. The All Wales Injury Surveillance System (AWISS) is a computerized system that collects injury data from most A&E departments throughout Wales. In this population-based study of 1.8 million people living in the 445 electoral tracts covered by AWISS in south, west, and northeastern Wales, we identified all 60,106 residents who presented with a fracture in 1999 and 2000. We linked details of their fracture with published Townsend deprivation scores for the electoral tract in which they were living and calculated fracture rates by fifths of deprivation. We observed the expected pattern of increasing fracture incidence in older age groups. Fracture incidence was significantly higher in electoral wards with poorer Townsend scores, resulting from a marked effect of socioeconomic deprivation on fracture incidence among younger adults with a rate ratio of 1.64 (95% CI, 1.57 to 1.72). This effect diminished with age, and was not observed in older age groups. At ages 85 and over the rate ratio was 0.94 (95% CI, 0.87 to 1.01). Socioeconomic factors clearly play a part in the causation of fracture in younger adults. Lifestyle influences are important in older age groups, but socioeconomic deprivation does not appear to be a risk factor for the development of osteoporotic fractures in elderly people.

  7. Understanding socio-economic inequalities in food choice behaviour: can Maslow's pyramid help?

    PubMed

    van Lenthe, Frank J; Jansen, Tessa; Kamphuis, Carlijn B M

    2015-04-14

    Socio-economic groups differ in their material, living, working and social circumstances, which may result in different priorities about their daily-life needs, including the priority to make healthy food choices. Following Maslow's hierarchy of human needs, we hypothesised that socio-economic inequalities in healthy food choices can be explained by differences in the levels of need fulfilment. Postal survey data collected in 2011 (67·2 % response) from 2903 participants aged 20-75 years in the Dutch GLOBE (Gezondheid en Levens Omstandigheden Bevolking Eindhoven en omstreken) study were analysed. Maslow's hierarchy of human needs (measured with the Basic Need Satisfaction Inventory) was added to age- and sex-adjusted linear regression models that linked education and net household income levels to healthy food choices (measured by a FFQ). Most participants (38·6 %) were in the self-actualisation layer of the pyramid. This proportion was highest among the highest education group (47·6 %). Being in a higher level of the hierarchy was associated with a higher consumption of fruits and vegetables as well as more healthy than unhealthy bread, snack and dairy consumption. Educational inequalities in fruit and vegetable intake (B= -1·79, 95 % CI -2·31, -1·28 in the lowest education group) were most reduced after the hierarchy of needs score was included (B= -1·57, 95 % CI - ·09, -1·05). Inequalities in other healthy food choices hardly changed after the hierarchy of needs score was included. People who are satisfied with higher-level needs make healthier food choices. Studies aimed at understanding socio-economic inequalities in food choice behaviour need to take differences in the priority given to daily-life needs by different socio-economic groups into account, but Maslow's pyramid offers little help.

  8. Declining reliance on marine resources in remote South Pacific societies: ecological versus socio-economic drivers

    NASA Astrophysics Data System (ADS)

    Turner, R. A.; Cakacaka, A.; Graham, N. A. J.; Polunin, N. V. C.; Pratchett, M. S.; Stead, S. M.; Wilson, S. K.

    2007-12-01

    Degraded coral reef ecosystems yield limited goods and services, which is expected to have significant socio-economic impacts on isolated tropical island communities with strong reliance on coral reefs. This study investigates socio-economic changes, specifically in fresh fish consumption and fishing activities, associated with environmental degradation at five fishing grounds ( qoliqoli) in the Lau Islands (Fiji). Semi-structured interviews with fishers and senior household members revealed that the importance of fishing was low relative to other occupations, and consumption of fresh fish has declined over the last decade. Reduced fishing and choice of fresh fish is largely attributable to an increased need to derive income as well as new income-generating opportunities. A possible consequence of reduced reliance on marine resources was limited awareness of recent environmental degradation caused by climate-induced coral bleaching and outbreaks of coral-feeding crown-of-thorns starfish. Limited use and reduced awareness of the local marine environment in the short term may erode social memory and local ecological knowledge, reducing opportunities to fall back on marine resources. This may also compromise long-term economic and social stability. Conversely, low reliance on marine resources may confer greater flexibility to adapt to future ecological change in the marine environment. Importantly, changes in fish consumption and exploitation of marine resources were linked to socio-economic factors rather than a consequence of recent degradation of marine environments. Greater knowledge of the dynamics driving change in marine resource use is necessary to understand how societies respond to ecological and socio-economic change, and to identify opportunities for adaptive sustainable ecosystem management.

  9. Socioeconomic Adversity and Women's Sleep: Stress and Chaos as Mediators.

    PubMed

    El-Sheikh, Mona; Keiley, Margaret; Bagley, Erika J; Chen, Edith

    2015-01-01

    We examined income-to-needs ratio, perceived economic well-being, and education and their relations with European and African American women's sleep (n = 219). Sleep was examined through actigraphy and self-reports. Income-to-needs ratio was related to sleep minutes. Perceived economic well-being and education were associated with subjective sleep problems. Perceived stress mediated relations between both income-to-needs ratio and economic well-being and subjective sleep problems. Chaos emerged as a mediator linking income-to-needs ratio and subjective sleep problems. African American women had fewer sleep minutes and lower sleep efficiency than European Americans, and more robust relations between economic well-being and stress was observed for European Americans. Findings highlight the importance of economic adversity for women's sleep and explicate some pathways of risk.

  10. The Relationship between Out-of-School-Suspension and English Language Arts Achievement of Students from Low Socio-Economic Settings

    ERIC Educational Resources Information Center

    Lobban, Carol Janet

    2012-01-01

    Out-of-school suspension (OSS) links low academic achievement to at risk students. Middle school students in one low socioeconomic urban setting experience lower academic achievement and higher rates of OSS. The purpose of this study was to determine the relationship between students' English Language Arts (ELA) achievement and OSS. Glasser's…

  11. Socioeconomic status in the treatment of depression.

    PubMed

    Falconnier, Lydia

    2009-04-01

    This study examined outcomes and attrition across three treatments for depression in relation to socioeconomic status (SES). The study was based on data available from the Treatment of Depression Collaborative Research Program (TDCRP) of the National Institute of Mental Health (NIMH; Elkin, 1994), a multisite collaborative study that examined the effectiveness of two forms of psychotherapy, cognitive behavior therapy and interpersonal psychotherapy, and pharmacotherapy. Results indicated that lower SES, measured by the Hollingshead Index of Social Position, was associated with less improvement across all three treatments for depression. The effect of SES on outcome did not differ by treatment modality. Contrary to expectations, SES was not associated with attrition. These findings suggest that there may be limitations in the use of these empirically validated treatments with lower SES depressed patients, as their improvement rates may be less than those of middle SES depressed patients treated by the same modalities. The results of this study also suggest that a standardized measure of SES may be more sensitive to SES differences in outcome than the more easily obtained measures of education or income. Suggestions are provided for additional research in this area to address the potential mediators and moderators of the association between SES and outcome.

  12. A study of suicide and socioeconomic factors.

    PubMed

    Ying, Yung-Hsiang; Chang, Koyin

    2009-04-01

    The topic of suicide has long been an important socioeconomic issue studied in many countries. Suicides inject an atmosphere of unrest into society, and media attention furthers that social uneasiness. From the viewpoint of economics and management, suicide is a waste of human resource: it decreases the labor force in society and deteriorates human capital. This paper provides a series of analyses of suicide rate based on theoretical reasoning and empirical approaches. Aggregate data from G7 countries are obtained and stacked into panel data for analysis. Data are collected for different age groups. Even though suicide issues have been extensively discussed in the past, newly developed econometric tools are applied to her. Beyond previously recognized relationships between economic factors and suicide rates findings include that unemployment strikes men more than women in terms of psychological pressure: for middle age or older women, unemployment may even be positive for the entire family; and female labor force participation exerts pressure on male counterparts and increases its suicide rate. As a result, a low income family with an unemployed man and an employed woman is at high risk for adult male suicide.

  13. Analyzing Optical Communications Links

    NASA Technical Reports Server (NTRS)

    Marshall, William K.; Burk, Brian D.

    1990-01-01

    Optical Communication Link Analysis Program, OPTI, analyzes optical and near-infrared communication links using pulse-position modulation (PPM) and direct detention. Link margins and design-control tables generated from input parameters supplied by user. Enables user to save sets of input parameters that define given link and read them back into program later. Alters automatically any of input parameters to achieve desired link margin. Written in FORTRAN 77.

  14. Life course socio-economic position and quality of life in adulthood: a systematic review of life course models

    PubMed Central

    2012-01-01

    Background A relationship between current socio-economic position and subjective quality of life has been demonstrated, using wellbeing, life and needs satisfaction approaches. Less is known regarding the influence of different life course socio-economic trajectories on later quality of life. Several conceptual models have been proposed to help explain potential life course effects on health, including accumulation, latent, pathway and social mobility models. This systematic review aimed to assess whether evidence supported an overall relationship between life course socio-economic position and quality of life during adulthood and if so, whether there was support for one or more life course models. Methods A review protocol was developed detailing explicit inclusion and exclusion criteria, search terms, data extraction items and quality appraisal procedures. Literature searches were performed in 12 electronic databases during January 2012 and the references and citations of included articles were checked for additional relevant articles. Narrative synthesis was used to analyze extracted data and studies were categorized based on the life course model analyzed. Results Twelve studies met the eligibility criteria and used data from 10 datasets and five countries. Study quality varied and heterogeneity between studies was high. Seven studies assessed social mobility models, five assessed the latent model, two assessed the pathway model and three tested the accumulation model. Evidence indicated an overall relationship, but mixed results were found for each life course model. Some evidence was found to support the latent model among women, but not men. Social mobility models were supported in some studies, but overall evidence suggested little to no effect. Few studies addressed accumulation and pathway effects and study heterogeneity limited synthesis. Conclusions To improve potential for synthesis in this area, future research should aim to increase study

  15. Children's and adolescents' sedentary behaviour in relation to socioeconomic position

    PubMed Central

    Coombs, Ngaire; Shelton, Nicola; Rowlands, Alex; Stamatakis, Emmanuel

    2013-01-01

    Background Sedentary behaviour is an emerging cardiometabolic risk factor in young people. Little is known about how socioeconomic position (SEP) and sedentary behaviour are associated in children and adolescents. This study examines associations between SEP and sedentary behaviour in school-age children and adolescents. Methods The core sample comprised 3822 Health Survey for England 2008 participants aged 5–15 years with complete information on SEP (household income, head of household occupational social class and area deprivation) and self-reported sedentary time (television viewing and other sitting during non-school times). Accelerometer-measured total sedentary time was measured in a subsample (N=587). We examined multivariable associations between SEP (including a composite SEP score) and sedentary time using generalised linear models, adjusting for age, sex, body mass index, physical activity, accelerometer wear time and mutually adjusting for the other SEP indicators. Results Participants in the highest SEP category spent 16 min/day less (95% CI 6 to 25, p=0.003) watching TV than participants in the lowest SEP category; yet they spent 7 (2 to 16, p=0.010) and 17 (5 to 29, p<0.000) min/day more in non-TV sitting and total (accelerometry-measured) sedentary time, respectively. Associations across individual SEP components varied in strength. Area deprivation was not associated with sedentary time. Conclusions Low SEP is linked with higher television times but with lower total (accelerometer-measured) sedentary time, and non-TV sitting during non-school time in children and adolescents. Associations between sedentary time and SEP differ by type of sedentary behaviour. TV viewing is not a good proxy for total sedentary time in children. PMID:23851152

  16. Targeting Wnt Pathways in Disease

    PubMed Central

    Zimmerman, Zachary F.; Moon, Randall T.

    2012-01-01

    Wnt-mediated signal transduction pathways have long been recognized for their roles in regulating embryonic development, and have more recently been linked to cancer, neurologic diseases, inflammatory diseases, and disorders of endocrine function and bone metabolism in adults. Although therapies targeting Wnt signaling are attractive in theory, in practice it has been difficult to obtain specific therapeutics because many components of Wnt signaling pathways are also involved in other cellular processes, thereby reducing the specificity of candidate therapeutics. New technologies, and advances in understanding the mechanisms of Wnt signaling, have improved our understanding of the nuances of Wnt signaling and are leading to promising new strategies to target Wnt signaling pathways. PMID:23001988

  17. Lower respiratory illness in infants and low socioeconomic status.

    PubMed Central

    Margolis, P A; Greenberg, R A; Keyes, L L; LaVange, L M; Chapman, R S; Denny, F W; Bauman, K E; Boat, B W

    1992-01-01

    OBJECTIVES. Infants from families of low socioeconomic status are said to suffer higher rates of lower respiratory illness, but this assertion has not been carefully examined. METHODS. We studied the frequency and determinants of lower respiratory illness in infants of different socioeconomic status (n = 393) by analyzing data from a community-based cohort study of respiratory illness during the first year of life in central North Carolina. RESULTS. The incidence of lower respiratory illness was 1.41 in the low socioeconomic group, 1.26 in the middle group, and 0.67 in the high group. The prevalence of persistent respiratory symptoms was 39% in infants in the low socioeconomic group, 24% in infants in the middle group, and 14% in infants in the high group. The odds of persistent respiratory symptoms in infants of low and middle socioeconomic status were reduced after controlling for environmental risk factors for lower respiratory illness. Enrollment in day care was associated with an increased risk of persistent symptoms among infants of high but not low socioeconomic status. CONCLUSIONS. Infants of low socioeconomic status are at increased risk of persistent respiratory symptoms. This risk can be partly attributed to environmental exposures, most of which could be changed. PMID:1636832

  18. Evolving Patient Compliance Trends: Integrating Clinical, Insurance, and Extrapolated Socioeconomic Data

    PubMed Central

    Klobusicky, Joseph J.; Aryasomayajula, Arun; Marko, Nicholas

    2015-01-01

    Efforts toward improving patient compliance in medication focus on either identifying trends in patient features or studying changes through an intervention. Our study seeks to provide an important link between these two approaches through defining trends of evolving compliance. In addition to using clinical covariates provided through insurance claims and health records, we also extracted census based data to provide socioeconomic covariates such as income and population density. Through creating quadrants based on periods of medicine intake, we derive several novel definitions of compliance. These definitions revealed additional compliance trends through considering refill histories later in a patient’s length of therapy. These results suggested that the link between patient features and compliance includes a temporal component, and should be considered in policymaking when identifying compliant subgroups. PMID:26958212

  19. Adherence to Airway Clearance Therapy in Pediatric Cystic Fibrosis: Socioeconomic Factors and Respiratory Outcomes

    PubMed Central

    Oates, Gabriela R.; Stepanikova, Irena; Gamble, Stephanie; Gutierrez, Hector H.; Harris, William T.

    2016-01-01

    Summary Objectives The evidence linking socioeconomic status (SES) and adherence in cystic fibrosis (CF) is inconclusive and focused on medication uptake. We examined associations between SES, adherence to airway clearance therapy (ACT), and CF respiratory outcomes. Study Design Socioeconomic, clinical, and adherence data of CF patients (N = 110) at a single CF Center were evaluated in this cross-sectional observational study. SES was operationalized as maternal and paternal education and household income. Adherence to ACT was measured with utilization data from the high-frequency chest wall oscillation (HFCWO) device over 4–6 weeks. Statistical modeling was used to test three hypotheses: (H1) Higher SES is associated with higher ACT adherence; (H2) Higher SES is associated with better respiratory outcomes; and (H3) ACT adherence mediates the relationship between SES and respiratory outcomes. Results In multinomial logistic regression, maternal college education, annual income >$50,000, and more adults in the household were independently related to better adherence (P < 0.05). Paternal college education, income >$100,000, and lack of exposure to smoking were independently related to higher lung function (P < 0.05). Current adherence to ACT with HFCWO was not associated with lung function over 12 months. Conclusions SES is associated both with ACT adherence and respiratory outcomes in pediatric CF patients. However, the link between SES and respiratory outcomes in this study was not mediated by adherence to ACT with HFCWO. These data emphasize the importance of socioeconomic resources and household environment for CF health. Family socio-demographic profiles can help identify patients at increased risk for ACT nonadherence. PMID:26436321

  20. Parental socioeconomic status and child intellectual functioning in a Norwegian sample.

    PubMed

    Eilertsen, Thomas; Thorsen, Anders Lillevik; Holm, Silje Elisabeth Hasmo; Bøe, Tormod; Sørensen, Lin; Lundervold, Astri J

    2016-10-01

    Socioeconomic status (SES) in childhood has been linked to cognitive function and future academic and occupational success in studies from several countries. However, previous Nordic studies have shown inconsistent results regarding the strength of this link. We therefore investigated the association between SES and cognitive functioning in a sample of 255 Norwegian children, including 151 typically developing children and 104 children with a psychiatric diagnosis. The third edition of the Wechsler Intelligence Scale for Children (WISC-III) to assess cognitive function was used. SES was defined from maternal and paternal education and family income of typically developing children and of a subsample of children with a psychiatric diagnosis. Multiple adjusted regression analyses were used to investigate the relation between SES and cognitive functioning. The analyses showed that SES explained a significant part of the variance of the full-scale WISC-III score and two WISC-III indices (Verbal Comprehension and Freedom from Distractibility). Overall, the strength of the relations was weaker than expected from reports from other non-Nordic countries. Parental education was the only significant individual predictor, suggesting that income was of minor importance as a predictor of cognitive functioning. Further studies should investigate how diverse political and socioeconomic contexts influence the relation between SES and cognitive functioning. PMID:27589048

  1. Social Capital, Information, and Socioeconomic Disparities in Math Coursework

    PubMed Central

    Crosnoe, Robert; Schneider, Barbara

    2011-01-01

    Analysis of the National Education Longitudinal Study revealed that socioeconomically advantaged students persist in high school math at higher rates than their disadvantaged peers, even when they have the same initial placements and skill levels. These disparities are larger among students with prior records of low academic status because students from more privileged backgrounds persist in math coursework even when their prior performance predicts they will not. Among students with low middle school math performance, those from socioeconomically disadvantaged families appear to benefit from having consultants for coursework decisions, so that they make up ground with their socioeconomically advantaged peers. PMID:21743762

  2. Breastfeeding, infant health, and socioeconomic status.

    PubMed

    Martorell, R; O'Gara, C

    1985-01-01

    This paper examines the relationship between infant feeding practices and infant growth in a study carried out in the slums of Tegucigalpa, Honduras. The following hypothese are tested: whether infants who are breastfed will grow better than infants who are bottlefed (infants who are both breastfed and bottlefed will occupy an intermediate position); whether the positive effect of breastfeeding and the negative impact of bottlefeeding will be enhanced after controlling for measures of socioeconomic status; and whether the magnitude of the effects that can be ascribed to breast and bottlefeeding decline with age such that by late infancy growth and health are less affected by milk feeding practice. Data were collected in a cross-sectional study in 1982 of low-income "barrios" of Tegucigalpa, the capital of Honduras. Data were collected by means of a household questionnaire and a physical examination of the infant. 912 households with living infants participated. Only households in which a birth had occurred in the 12 months preceding the interview were included. The following conclusions resulted from the study: infants who are breastfed grow better than infants who are bottle fed; infants who were both bottle-and breastfed occupied the intermediate position in terms of growth; controlling for potentially confusing factors tended to make associations with breastfeeding more positive and more negative with bottlefeeding; the results indicate stronger, more consistent associations in the 1st 9 months of life than in the period from 9 to 12 months. Breastfeeding is best through infancy, and then supplementary feeding is required.

  3. Socioeconomic status and fertility in rural Bangladesh.

    PubMed

    Shaikh, K; Becker, S

    1985-01-01

    Using a unique set of birth registration data from the Demographic Surveillance System of the International Center for Diarrheal Disease Research, Bangladesh, for the period 1974-77, and socioeconomic information collected in the 1974 census, fertility was studied in relation to occupation, size of dwelling, number of cows and number of boats owned. The total fertility rate was found to vary between 6 and 6.5 except in the famine year of 1975. There was no consistent relationship between fertility and education of women. The age-specific fertility rates by religion show that Muslims had higher fertility at all ages in 1974 and 1977 and at older ages in 1975 and 1976. Overall, however, fertility of Hindus is consistently lower than that of Muslims, but the relative differences are under 10%. Fertility differentials by occupation showed that the household heads who were farm laborers had relatively lower fertility compared to other occupational groups, except for the year 1977 where the families of service holders were found to have relatively lower fertility. Women in households whose heads were businessmen or farmers (owning their land) had above average fertility. In 1974, households in the business occupational groups had, on average, 1 birth more than other households. Women in households with fishermen as heads had below average fertility in 1974 and 1975, but very high fertility in 1976 and 1977. Fertility levels differed according to the type of household in which the family resided. Nuclear families had below average fertility up to the age of 35 and above average fertility at the end of the reproductive age. In the 15-19 age group, augmented families had higher fertility each year examined. The association between dwelling place and fertility is positive each year, the relative differences in fertility between the groups being largest in 1974. Positive relations were found between economic status and fertility. PMID:3972858

  4. Cross-sectional Study on the Effects of Socioeconomic Factors on Lead Exposure in Children by Gender in Serpong, Indonesia

    PubMed Central

    Iriani, Dewi U.; Matsukawa, Takehisa; Tadjudin, Muhammad K.; Itoh, Hiroaki; Yokoyama, Kazuhito

    2012-01-01

    To elucidate the socioeconomic factors influencing lead exposure in elementary school children by gender, 108 children (56 male, 52 female), aged 6–7 years, were randomly selected from 39 elementary state schools in Serpong, Banten, Indonesia. Their parents were interviewed to obtain information on sociodemographic characteristics. Their blood lead (BPb) levels were measured by atomic absorption spectrophotometry. BPb concentrations were significantly higher in males than in females, i.e., 6.8 ± 2.0 (2.9–12.5) µg/dL and 5.9 ± 1.9 (3.1–11.7) µg/dL, respectively (p < 0.05). Lower socioeconomic status and well water use were associated with increased BPb concentrations, especially in females. The proportion of well water use was related to lower socioeconomic status. Lower socioeconomic status linked with well water drinking seemed to be associated with increased lead exposure in children in Serpong. Their exposure levels possibly varied according to gender differences in behavior. An intervention should be instituted among children in Serpong with BPb concentrations of 10 µg/dL or above. PMID:23202836

  5. Family socioeconomic status, family health, and changes in students' math achievement across high school: A mediational model.

    PubMed

    Barr, Ashley Brooke

    2015-09-01

    In response to recent calls to integrate understandings of socioeconomic disparities in health with understandings of socioeconomic disparities in academic achievement, this study tested a mediational model whereby family socioeconomic status predicted gains in academic achievement across high school through its impact on both student and parent health. Data on over 8000 high school students in the U.S. were obtained from wave 1 (2009-2010) and wave 2 (2012) of the High School Longitudinal Study of 2009 (HSLS:09), and structural equation modeling with latent difference scores was used to determine the role of family health problems in mediating the well-established link between family SES and gains in academic achievement. Using both static and dynamic indicators of family SES, support was found for this mediational model. Higher family SES in 9th grade reduced the probability of students and their parents experiencing a serious health problem in high school, thereby promoting growth in academic achievement. In addition, parent and student health problems mediated the effect of changes in family SES across high school on math achievement gains. Results emphasize the importance of considering the dynamic nature of SES and that both student and parent health should be considered in understanding SES-related disparities in academic achievement. This relational process provides new mechanisms for understanding the intergenerational transmission of socioeconomic status and the status attainment process more broadly.

  6. Contribution of food prices and diet cost to socioeconomic disparities in diet quality and health: a systematic review and analysis

    PubMed Central

    Drewnowski, Adam

    2015-01-01

    Context: It is well established in the literature that healthier diets cost more than unhealthy diets. Objective: The aim of this review was to examine the contribution of food prices and diet cost to socioeconomic inequalities in diet quality. Data Sources: A systematic literature search of the PubMed, Google Scholar, and Web of Science databases was performed. Study Selection: Publications linking food prices, dietary quality, and socioeconomic status were selected. Data Extraction: Where possible, review conclusions were illustrated using a French national database of commonly consumed foods and their mean retail prices. Data Synthesis: Foods of lower nutritional value and lower-quality diets generally cost less per calorie and tended to be selected by groups of lower socioeconomic status. A number of nutrient-dense foods were available at low cost but were not always palatable or culturally acceptable to the low-income consumer. Acceptable healthier diets were uniformly associated with higher costs. Food budgets in poverty were insufficient to ensure optimum diets. Conclusions: Socioeconomic disparities in diet quality may be explained by the higher cost of healthy diets. Identifying food patterns that are nutrient rich, affordable, and appealing should be a priority to fight social inequalities in nutrition and health. PMID:26307238

  7. Effects of parental socio-economic conditions on facial attractiveness.

    PubMed

    Huber, Susanne; Fieder, Martin

    2014-12-30

    Socio-economic conditions during early life are known to affect later life outcomes such as health or social success. We investigated whether family socio-economic background may also affect facial attractiveness. We used the Wisconsin Longitudinal Study (n = 8434) to analyze the association between an individual's parental socio-economic background (in terms of father's highest education and parental income) and that individual's facial attractiveness (estimated by rating of high school yearbook photographs when subjects were between 17 and 20 years old), controlling for subjects' sex, year of birth, and father's age at subjects' birth. Subjects' facial attractiveness increased with increasing father's highest educational attainment as well as increasing parental income, with the latter effect being stronger for female subjects as well. We conclude that early socio-economic conditions predict, to some extent, facial attractiveness in young adulthood.

  8. Socioeconomic inequalities and diabetes: A systematic review from Iran.

    PubMed

    Peykari, Niloofar; Djalalinia, Shirin; Qorbani, Mostafa; Sobhani, Sahar; Farzadfar, Farshad; Larijani, Bagher

    2015-01-01

    Socioeconomic factor is a determinant of health may contribute to diabetes. We conducted a systematic review to summarizing evidences on associations between socioeconomic factors and diabetes in Iranian population. We systematically searched international databeses; ISI, PubMed/Medline, Scopus, and national databases Iranmedex, Irandoc, and Scientific Information Database (SID) to retrieve relevant articles to socioeconomic factors and diabetes without limitation on time. All identified articles were screened, quality assessed and data extracted by two authors independently. From 74 retrieved articles, 15 cases were relevant. We found increased diabetes prevalence among female sex, over 50 years' old age, illiterate population, retired status, unemployed, urban residents, and low economic status. There was a negative association between social capital and diabetes control. Diabetes complications were more frequent in upper age group, higher education levels and low income populations. Socioeconomic factors were associated with diabetes that leads to inequality. Improving modifiable factors through priority based interventions helps to diabetes prevention and control.

  9. 76 FR 26220 - Federal Acquisition Regulation; Socioeconomic Program Parity

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-06

    ... Register of Wednesday, March 16, 2011 (76 FR 14568). The regulations implement section 1347 of the ``Small... Federal Acquisition Regulation; Socioeconomic Program Parity AGENCY: Department of Defense (DoD),...

  10. Minimization of socioeconomic disruption for displaced populations following disasters.

    PubMed

    El-Anwar, Omar; El-Rayes, Khaled; Elnashai, Amr

    2010-07-01

    In the aftermath of catastrophic natural disasters such as hurricanes, tsunamis and earthquakes, emergency management agencies come under intense pressure to provide temporary housing to address the large-scale displacement of the vulnerable population. Temporary housing is essential to enable displaced families to reestablish their normal daily activities until permanent housing solutions can be provided. Temporary housing decisions, however, have often been criticized for their failure to fulfil the socioeconomic needs of the displaced families within acceptable budgets. This paper presents the development of (1) socioeconomic disruption metrics that are capable of quantifying the socioeconomic impacts of temporary housing decisions on displaced populations; and (2) a robust multi-objective optimization model for temporary housing that is capable of simultaneously minimizing socioeconomic disruptions and public expenditures in an effective and efficient manner. A large-scale application example is optimized to illustrate the use of the model and demonstrate its capabilities ingenerating optimal plans for realistic temporary housing problems.

  11. School socioeconomic composition and adolescent sexual initiation in Malawi

    PubMed Central

    Kim, Jinho

    2015-01-01

    While numerous studies have documented the determinants of sexual behavior among adolescents in less developed countries, relatively little is known about the influence of social contexts such as school and neighborhood. Using two waves of data from a school-based longitudinal survey conducted in Malawi from 2011 to 2013, this study advances our understanding of the relationship between school-level socioeconomic contexts and adolescents’ sexual activity. The results from two-level multinomial logistic regression models suggest that high socioeconomic composition of the student body in school decreases the odds of initiating sexual activity, independently of other important features of schools as well as individual-level characteristics. This study also finds that the association between school socioeconomic composition and sexual activity is statistically si